English
聯系我們
網站地圖
郵箱
舊版回顧



科學家繪制造血干細胞擴增組織的3D轉錄組圖譜

文章來源:動物研究所   發布時間:2019-05-10  【字號:     】  

  血液系統中貯藏著一種具有自我更新、分化成各種血細胞潛能的成體干細胞,稱為造血干細胞,它能夠維持機體長久造血和組織穩態。造血干細胞移植是惡性血癌的有效治療手段,但干細胞來源不足成為限制該治療廣泛應用的瓶頸。因此,造血干細胞的發育,尤其是造血干細胞擴增的研究備受關注。然而,現在的研究主要集中在特定細胞群體或關鍵因子的“線性化”或“平面化”解析,缺乏全面“立體化”的分析。從系統生物學角度解析擴增性造血器官,將為造血干細胞擴增的機制研究提供更多的啟示。鑒于造血發育過程的高度保守性,中國科學院動物研究所劉峰研究組及合作者以斑馬魚尾部造血組織(在功能上類似于哺乳動物的胎肝,為造血干細胞擴增及分化提供了特定的微環境)為研究對象,利用多重轉錄組測序的方法,繪制了擴增性造血器官的3D轉錄組圖譜,闡釋了造血干細胞和微環境細胞之間的分子調控網絡。

  首先,為了系統性地研究斑馬魚尾部造血組織如何支持造血干細胞擴增、分化的機制,劉峰實驗室利用三種轉錄組測序方法,特定類型群體細胞轉錄組、空間轉錄組和單細胞轉錄組,詳細解析了斑馬魚尾部造血組織的時空特性。不同發育時期特定細胞群體的轉錄組測序分析表明,造血干細胞與相應微環境細胞具有協同發育和共享基因表達的特點。空間轉錄組測序反映細胞位置信息,揭示了多種微環境因素對造血干細胞的不同調控方式,并實現了三維轉錄組重構斑馬魚造血器官。單細胞轉錄組數據更精細闡釋尾部造血組織細胞類群、細胞特征及細胞間分子調控,并發現造血干祖細胞分化和細胞周期存在一定的關聯性。多重轉錄組測序綜合分析揭示了造血干細胞在尾部造血組織的擴增受到內源性和外源性信號的共同調控,鑒定了新的造血干細胞的標記基因,發現了影響造血干細胞擴增的信號通路,完善了造血干細胞-微環境細胞間分子調控網絡。例如,染色質結構維持蛋白smchd1,通過調節造血干細胞增殖促進其擴增;微環境細胞來源的Integrin 信號通路負向調控造血干細胞擴增。同時此項工作還構建了斑馬魚尾部造血組織多重轉錄組數據庫(http://www.picb.ac.cn/hanlab/ichtatlas/Home),可以檢索任何基因在造血組織的表達譜,包括基因表達的時間、細胞類型及相對空間位置。

  該工作不僅發現了造血干細胞特征基因、細胞狀態與細胞分化的關系,闡釋了微環境和造血干細胞互作的調控網絡,更為血液系統研究提供了豐富的數據資源;同時,也將為造血干細胞的體外擴增和造血類器官的體外組裝提供理論指導。該研究論文“A 3D atlas of hematopoietic stem and progenitor cell expansion by multi-dimensional RNA-seq analysis430日在線發表于Cell Reports

  動物所博士研究生薛媛媛和中科院計算生物學研究所博士研究生劉登輝為文章共同第一作者,動物所研究員劉峰和計算生物學所研究員韓敬東為文章共同通訊作者。中科院生物化學與細胞生物學研究所研究員景乃禾與中科院廣州生物醫藥與健康研究院研究員彭廣敦在空間轉錄組測序方面提供了大力支持。該研究得到國家自然科學基金委、國家重點基礎研究發展計劃和中科院器官重建與制造戰略性先導科技專項的資助。

 

  圖1:多重轉錄組測序解析斑馬魚造血器官。多重轉錄組測序,包括:特定類型群體細胞轉錄組測序、空間轉錄組測序和單細胞轉錄組測序,揭示斑馬魚尾部造血組織的時空特性。

 

圖2:斑馬魚造血器官轉錄組數據庫 




(責任編輯:葉瑞優)

附件:

專題推薦

相關新聞


© 1996 - 中國科學院 版權所有 京ICP備05002857號  京公網安備110402500047號  聯系我們

地址:北京市三里河路52號 郵編:100864

彩82www.c6313.com www.50505.cc | www.218894.com | www.307589.com | www.522775.com | www.393516.com | www.964738.com | www.33527.cc | www.01058.com | www.24199.com | www.134248.com | 493148.com | www.181050.com | www.134279.com | www.611856.com | 新盈彩www.xinyc2.com | www.56753.com | 皮皮彩www.105180.com | www.865638.com | www.676543.cc | 08335.com | 老彩票www.775790.com | www.048300.com | www.350791.com | www.400934.com | www.459.pw | www.4379.biz | www.x68.biz | www.mc80.com | www.81524.com | www.318430.com | www.447821.com | www.964147.com | www.97jf.com | www.cp7577.com | www.53ve.com | www.107628.com | www.524800.com | 499830.com | 927654.com | 203456.com | www.4865.xyz | www.xa46.com | www.983320.com | 7091.biz | 天天中彩票www.399957.com | www.gh25.com | www.92in.com | www.59629.com | 500彩票www.50080w.com | www.231259.com | www.697679.com | www.803128.com | www.9229.top | www.611545.com | www.741729.com | www.52882.cc | www.606525.com | www.778057.com | 990682.com | www.838991.com | www.804229.com | www.414062.com | www.446826.com | www.896771.com | www.822354.com | 790168.com | www.176275.com | www.sk25.com | www.98qk.com | www.128037.com | 232792.com | www.535567.com | www.652229.com | www.273485.com | www.cp052.com | www.53ut.com | www.29je.com | www.303625.com | www.22ly.com | www.965764.com | www.cp3697.com | 570529.com | 777810.com | 优彩网www.987425.com | www.921203.com | 福彩www.86267j.com | www.085976.com | www.676968.com | www.250106.com | www.104723.com | www.160930.com | www.c94.cc | www.40009.com | www.316678.com | 中华彩票www.9149b.com | www.22bv.com | www.11825.cc | www.079097.com | www.480228.com | 141775.com | www.982194.com | 884156.com | www.pv38.com | 378234.com | 456444.cc | www.926289.com | www.dc32.com | 573143.com | www.06911.com | www.058279.com | www.cp701.com | www.vb23.com | www.86918.com | www.5130.biz | www.2dq.cc | www.853941.com | www.qy05.com | www.803721.com | www.fc2.com | www.2879.net | www.9719.biz | www.173677.com | www.368880.com | www.qy15.com | www.85795.com | www.240166.com | www.398276.com | www.632587.com | www.zl58.com | www.637645.com | www.982510.com | www.956443.com | www.990263.com | 788785.com | 550948.com | www.6477.xyz | www.8853.win | www.47574.com | www.047556.com | www.226055.com | www.4669.xyz | www.21379.cc | www.390031.com | www.615714.com | www.943655.com | www.751068.com | www.857807.com | www.653942.com | 23883.com | www.77893.com | www.448456.com | www.645585.com | www.428838.com | www.022912.com | www.712776.com | www.9207.vip | www.552249.com | 022271.com--135888.com | www.70089.cc | www.578028.com | www.39pz.cc | www.e24.org | www.867756.com | www.929193.com | www.8144.vip | www.057629.com | www.039316.com | www.112319.com | www.013931.com | www.092322.com | www.643.xyz | www.18158.com | www.970504.com | www.972783.com | www.974250.com | www.038339.com | www.61zi.com | www.o25.net | www.210559.com | 076983.com | 680385.com | www.384814.com | www.790209.com | www.79id.com | www.hn29.com | www.55357.cc | 452211.com | www.166066.com | 56ag.com | www.ki38.com | 233589.com | www.682675.com | www.777902.com | www.778595.com | www.108702.com | www.234141.com | www.51yw.cc | www.63043.com | www.277606.com | www.128955.com | www.254515.com | 295336.com | www.cp6775.com | www.678519.com | www.692193.com | www.727856.com | www.825728.com | www.877660.com | www.943508.com | www.742766.com | 984070.com | 630736.com | 514165.com | www.986302.com | www.yu71.com | www.2128.org | www.130790.com | www.584748.com | www.574230.com | www.644699.com | 聚彩网www.290282.com | www.0407.org | www.081253.com | www.033364.com | www.79611.com | www.191136.com | www.486223.com | www.567688.com | www.839158.com | www.95658.com | www.034076.com | www.256556.com | www.369236.com | 502567.cc | 249411.com | www.97211.cc | www.301307.com | www.337363.com | www.407119.com | www.537962.com | www.549504.com | www.67789.com | www.331948.com | www.591577.com | www.828538.com | www.572470.com | www.759848.com | www.781436.com | www.918114.com | www.253325.com | www.128899.cc | 549721.com | www.vk79.com | www.nx32.com | www.731120.com | www.773792.com | www.668561.com | www.236879.com | www.384975.com | www.556954.com | www.895711.com | www.957586.com | www.911543.com | www.189340.com | www.049887.com | www.450069.com | www.yy44.cc | www.777229.com | www.72838.cc | www.561379.com | www.034534.com | www.780698.com | www.pg00.cc | www.609275.com | www.31hh.cc | www.77vm.com | www.90391.com | www.089794.com | www.cp2828.com | www.898359.com | www.769062.com | www.388979.com | www.533146.com | www.175283.com | www.337968.com | www.213854.com | www.881323.com | 355476.com | 全民乐彩票www.2934e.com | www.785874.com | www.712787.com | www.732127.com | www.858.me | www.85268.com | www.19yg.com | www.726.me | www.9236.org | 338946.com | 134258.com | www.217337.com | www.226930.com | www.383444.com | www.566833.com | www.665647.com | www.928019.com | www.n99.org | www.751731.com | www.911.hk | www.577056.com | www.5578.wang | www.309432.com | www.165500.com | www.917608.com | 凤凰彩票www.88266p.com | 209187.com | www.749103.com | www.127212.com | 662870.com | 251792.com | www.3lj.com | www.5349.pw | www.9480.loan | www.410482.com | www.266993.com | www.458057.com | www.005309.com | www.057120.com | www.888976.com | www.136146.com | 867717.com | 998118.com | www.198366.com | www.274621.com | www.90500.cc | www.60002.com | www.349422.com | www.375520.com | www.14124.com | www.741241.com | 16彩票www.331616.com | www.018461.com | www.072803.com | www.121475.com | www.710193.com | www.4723.top | www.290.live | www.452711.com | 638249.com | 963971.com | www.299610.com | www.271082.com | 349561.com | www.885859.com | www.591820.com | www.071701.com | www.101107.com | www.566741.com | www.313855.com | www.994059.com | www.021092.com | www.030747.com | www.140.bid | www.ps60.com | www.10479.com | www.95126.com | www.03ra.com | www.525481.com | www.563382.com | www.698617.com | www.696162.com | www.753361.com | www.7226.cn | www.577007.com | www.118350.com | www.697825.com | www.825493.com | 945096.com | www.7744.cm | 751049.com | www.235557.com | www.831182.cc | www.872107.com | www.146785.com | www.625881.com | www.254577.com | www.83566.cc | www.425544.com | wz79.com | www.33qp.cc | www.4821.biz | www.009742.com | www.155189.com | www.371341.com | 028304.com | www.039066.com | www.085089.com | www.820658.com | www.qh28.com | www.67rg.com | www.957624.com | www.5373.top | www.691468.com | www.658325.com | www.329922.com | www.330202.com | 949372.com | 669217.com | pk08.com--www.pk08.com | 886334.com--pjc55.com | 杏彩www.00840f.com | www.cai5123.com | www.56095.com | www.39199p.com | www.582648.com | www.887801.com | 500万彩票www.35155a.com | www.26nz.com | www.47470.cc | www.7413.cn | d84.cc | www.688682.com | www.38223.cc | 973440.com | 947069.com | www.89647.com | www.086698.com | 262694.com | www.00ki.com | www.69yy.cc | www.02909.com | www.852813.com | www.1104.vip | www.4247.cm | www.645099.com | www.583372.com | www.qe86.com | www.384901.com | www.421878.com | www.518352.com | www.26cw.com | www.zh06.com | 397649.com | www.0318.name | www.0966.bid | www.948.win | www.911.net | www.036770.com | www.025674.com | www.223248.com | www.268939.com | 230472.com | www.59335.com | www.586727.com | www.964519.com | www.1361.net | www.073619.com | www.hs40.com | www.6495.xyz | www.73qc.com | www.0161.vip | 728771.com | www.006816.com | www.717337.com | 496769.com | 966485.com | www.67dt.com | www.2851.top | www.1907.vip | www.2878.com | www.8066.in | www.3752.wang | www.39dy.com | 129754.com | 470061.com | www.hz34.com | www.153846.com | www.96ba.com | www.71cw.com | www.15nc.com | www.640650.com | www.308275.com | 235389.com | 282234.com | www.365706.com | www.477999.cc | www.506772.com | www.jq44.com | 136725.com | wank3.com | www.872393.com | 彩票坊www.775979.com | www.cz95.com | www.228240.com | 943958.com | www.fj08.com | www.96bi.com | 343533.com | www.bq97.com | www.758895.com | www.810495.com | www.947370.com | www.05540.com | www.85tq.com | www.883101.com | 971435.com | 613381.com | 61939.com | www.028574.com | 298435.com | www.185594.com | www.005470.com | www.083533.com | www.619757.com | www.320959.com | www.328661.com | www.905278.com | www.169362.com | www.182285.com | www.ke44.com | www.q62.club | 751241.com | 彩票坊www.476669.com | 952906.com | www.799251.com | www.673527.com | www.432415.com | www.2043.vip | www.872264.com | 240233.com | yk61.com | 320008.com | 975147.com | www.lb85.com | www.630516.com | www.932290.com | www.730810.com | www.580836.com | www.12ir.com | www.086638.com | www.902392.com | www.783115.com | www.987906.com | www.461511.com | www.372733.com | www.322806.com | www.289351.com | www.799799.cc | www.741199.com | 212477.com | 74450.com | www.159059.com | www.025544.com | www.f93.com | www.pj53.com | www.374288.com | www.142334.com | www.480072.com | www.822027.com | www.149869.com | 949821.com | www.441694.com | www.956006.com | 937798.com | www.299621.com | www.130609.com | www.826736.com | www.667481.com | www.593015.com | www.4456.vip | 4568.biz | www.97973.com | www.571359.com | www.mm95.com | www.xq26.com | www.124033.com | 大赢家彩票网www.178397.com | 910067.com | 122714.com | www.543103.com | 云博彩票www.05883.cc | pj91.cc | www.910698.com | www.476519.com | www.001451.com | www.346100.com | www.hc73.cc | www.l04.com | 325846.com | www.838955.com | www.734368.com | www.897108.com | www.5703.me | www.786500.com | www.346618.com | www.434420.com | www.57721.cc | www.1959.win | www.425178.com | www.381884.com | www.788667.com | www.879008.com | 552249.com | 495163.com | 958407.com | www.903968.com | www.721152.com | www.jh03.com | www.438722.com | www.380022.com | 2240.cc | www.877607.com | www.860263.com | www.858472.com | 152638.com | 杏彩www.00840l.com | 百姓彩票www.bxcp4.com | 621770.com | 99彩票www.865606.com | 896501.com | www.092056.com | www.617525.com | 340869.com | www.61sa.com | www.6514.com | www.yv4.com | www.kh84.com | www.9512.shop | www.805310.com | 亿万彩票www.805595.com | www.494334.com | www.939133.com | www.525679.com | www.598363.com | www.592868.com | www.96648.com | www.728298.com | www.339788.com | www.835370.com | www.132229.com | www.059004.com | www.17614.com | www.2496.vip | www.876163.com | www.l83.shop | www.056154.com | www.466578.com | www.r72.cn | www.444636.com | www.106168.com | www.946821.com | www.678249.com | www.539808.com | www.121520.com | www.41790.com | www.377140.com | www.651192.com | 688773.com | www.057063.com | www.34856.com | www.37205.com | www.028308.com | 114832.com | www.cp1719.com | fm88.cc | www.48219.com | www.018832.com | www.87299.com | www.3799.cn | www.867313.com | www.0201.cm | www.22531.com | www.3603.me | www.555145.com | www.255430.com | www.040693.com | www.271244.com | www.67iv.com | www.918857.com | www.907576.com | www.805477.com | 989780.com | www.5957.cm | www.070858.com | www.903449.com | www.xy24.com | 351969.com | 649135.com | 489438.com | www.cai122.cc | 918894.com | www.312281.com | www.978959.com | www.931667.com | www.11283.cc | www.cai4511.com | 209344.com | www.986427.com | www.000900.com | www.k57.net | www.443543.com | 872863.com | www.x44.cc | www.318504.com | www.100205.com | 必发彩票www.935506.com | www.25824.com | www.361468.com | www.ar99.com | 451271.com | lo32.com | 3516.biz | www.958641.com | www.78vo.com | www.60302.com | www.6333.tv | www.1fo.com | www.tu73.com | www.61ns.com | 564122.com | www.975670.com | www.095597.com | www.539043.com | www.189104.com | www.399262.com | www.894763.com | www.979499.com | 358040.com | www.626652.com | www.581274.com | www.411700.com | www.4340.cm | www.276725.com | www.982403.com | www.611380.com | www.xs07.com | www.978.org | www.51mu.cc | www.699869.com | www.749486.com | www.973994.com | 亚洲彩www.68568u.com | www.197695.com | www.115960.com | www.957434.com | www.613580.com | www.986888.com | www.62ds.com | 天天彩票www.106036.com | 908558.com | www.022146.com | www.202227.com | www.098204.com | www.93466.cc | www.219944.com | www.338674.com | www.625908.com | www.200549.com | www.171865.cc | www.891688.com | www.653885.com | www.758268.com | www.3818.cn | 天下彩www.946689.com | 501831.com | www.386408.com | www.91505.cc | www.960284.com | www.34yf.com | www.295078.com | 博汇www.865850.com | www.119667.com | www.672748.com | www.012312.com | www.15ct.com | 513013.com | 241938.com | www.25655.com | www.56sg.com | www.og07.com | www.54075.com | www.6604.vip | www.529075.com | www.343178.com | www.17go.cc | www.ht3.com | 078049.com | 025083.com | www.983335.com | www.773017.com | www.600940.com | www.813754.com | 697302.com | 115744.com | 415817.com | 6591.biz | 312532.com | 657357.com | www.933829.com | www.859730.com | www.963966.com | www.977497.com | www.790709.com | www.388803.com | www.716881.com | www.456767.com | 011292.com | s63.vip | 924705.com | www.220279.com | 653003.com | 994907.com | www.881311.com | 708400.com--www.beijing918.com | www.667898.cc | www.428136.com | www.3333.cn | www.723829.com | www.858241.com | www.984606.com | www.2588.pw | www.225349.com | www.1989.org | www.329078.com | www.l43.cn | www.07fu.com | 网易彩票www.082wy.com | www.132583.com | www.711788.com | www.994650.com | www.yz90.com | www.848827.com | www.78375.com | www.450375.com | www.982984.com | 500彩票www.66653g.com | 855042.com | 239812.com | www.910660.com | www.282519.com | 149234.com | www.8gc.com | www.4967.biz | 557093.com | www.949514.com | www.314115.com | www.062952.com | www.958747.com | www.002170.com | www.061866.com | www.19091.com | www.gw05.com | www.89di.com | 950590.com | www.425092.com | www.035151.com | www.462898.com | 111796.com | www.958452.com | www.479365.com | www.98277.com | www.59599.cc | www.008717.com | www.78596.com | www.85928.cc | www.949763.com | www.180053.com | www.066231.com | www.020594.com | www.251957.com | www.66330.cc | www.6199.top | www.250077.com | www.142811.com | www.188693.com | www.000411.com | www.676187.com | www.279672.com | www.kd20.com | www.310966.cc | www.169714.com | www.616750.com | 501951.com | www.942205.com | www.877311.com | www.562795.com | www.272828.com | 707383.com | www.854080.com | 951431.com | www.393600.com | www.iz2.cc | 314059.com | www.159395.com | www.80zl.com | www.vt82.com | www.639066.com | www.521662.com | www.56cj.com | www.18196.cc | www.95ct.com | www.815351.com | www.580508.com | www.24627.com | www.396892.com | www.287854.com | www.503228.com | www.781624.com | www.83sk.com | www.zi90.com | www.685699.com | 496977.com | 573113.com | 829947.com | www.772962.com | www.876287.com | www.495010.com | oj04.com | 536234.com | www.cp9110.com | www.ir44.com | 501520.com | 973352.com | www.852216.com | www.709295.com | 831385.com | www.4966.cc | www.367520.com | www.957291.com | www.930793.com | www.299119.com | www.760917.com | www.tz13.com | 199833.com | www.728018.com | www.313113.com | www.945356.com | www.416440.com | www.755500.com | 188345.com | 500彩票www.807979.com | www.88031.com | www.2570.vip | www.22sb.com | www.123854.com | www.cai1115.com | 306561.com | www.845744.com | www.171926.com | www.836739.com | 043541.com | 460037.com | www.0153.net | www.510515.com | www.9646.cm | www.17qv.com | cai2226.com | www.897231.com | www.757104.com | www.101468.com | www.77226.cc | www.q00.cc | www.181931.com | www.697005.com | 284380.com | www.18263.com | www.020000.com | www.780007.com | 博友彩www.978913.com | www.604298.com | www.4562.pw | www.178378.com | www.901498.com | www.570.cm | www.tg93.com | 984073.com | www.990943.com | www.247682.com | www.98750.com | www.5113.cn | www.64eh.com | 769603.com | www.840311.com | www.589813.com | www.345663.com | www.92804.com | www.355927.com | www.114286.com | www.6948.xyz | www.qq98.com | 51彩票www.34972.com | 03m.pw | www.685303.com | www.219850.com | www.93149.com | www.65hi.com | 大赢家彩票www.599474.com | www.12ra.com | 572219.com | www.904881.com | www.678155.com | www.294900.com | www.74825.com | www.36793.cc | 805286.com | 944365.com | www.680560.com | 231271.com | 009403.com | 853649.com | www.960164.com | www.607570.com | www.265403.com | www.96311.cc | www.0222.me | www.316522.com | 010078.com | 372271.com | www.7830.cm | www.be05.com | www.948285.com | www.70708.cc | www.25tk.com | www.um73.com | ux32.com | www.096616.com | www.619168.com | 943178.com | www.wd39.com | www.486046.com | www.66169.cc | www.496543.com | www.322783.com | 087744.com | www.994420.com | 66244.cc | 181469.com | 662718.com | www.931411.com | www.6770.vip | www.ni48.com | www.2779.wang | www.875455.com | www.556287.com | 248825.com | 7063.biz | www.3fv.cc | www.112289.com | www.834230.com | 中国福利彩票www.34788o.com | 628090.com | 417526.com | www.59tp.com | www.r58.cc | www.8443.cn | www.os77.com | www.279508.com | www.65jg.com | www.8546.cc | 大赢家彩票网www.544094.com | 653181.com | www.962417.com | www.76668.cc | www.930711.com | www.824771.com | 237763.com | www.32851.com | 008390.com | www.816068.com | www.579178.com | www.286000.com | www.066130.com | www.520122.com | www.128154.com | www.9023.biz | www.jk25.com | 659863.com | 5857.biz | www.866113.com | www.883335.com | www.144081.com | www.91951.com | www.46276.com | www.454343.com | www.111702.com | www.6176.cm | www.rq7.com | www.228590.com | www.51424.com | www.731436.com | www.393033.com | 47130.com | 237111.com | www.257164.com | www.019346.com | www.0199.vip | 190399.com | www.762950.com | 163648.com | www.855157.com | www.206822.com | 329987.com | www.964339.com | www.72264.com | www.34703.com | 791714.com | www.989881.com | www.830249.com | www.573786.com | www.761430.com | 百姓彩票www.bxcp3.com | www.125204.com | 480116.com | 947170.com | 358496.com | 301031.com | 850311.com | www.1528.cm | www.477714.com | www.553062.com | www.z56.net | www.7530.in | www.334003.com | www.51025.com | www.1460.live | www.984629.com | 989323.com | www.629302.com | www.274612.com | 731745.com | www.33502.com | www.t12.tv | www.62020.com | www.bj63.com | 161304.com | www.01477.com | www.360942.com | www.020897.com | www.95ch.com | www.2171.biz | www.148.tv | 659475.com | www.097220.com | www.24762.com | www.153365.com | www.15051.com | www.f24.club | www.02uk.com | www.26966.cc | www.4326.com | www.290453.com | 99福彩www.761996.com | 959450.com | 083739.com | www.654465.com | www.331220.com | www.62687.cc | www.077244.com | www.27648.com | www.277534.com | www.664881.com | www.127454.com | www.8sc.cc | 951483.com | 194368.com | gt88.com | www.582622.com | 940026.com | www.979471.com | www.584605.com | www.872507.com | www.523930.com | www.771829.com | www.687571.com | www.339944.com | www.012190.com | www.4307.win | www.cp742.com | www.962198.com | www.30901.com | www.9090.tv | www.692.website | www.95668.com | www.32559.cc | www.63vu.com | www.620313.com | www.407552.com | www.916687.com | www.930868.com | www.460543.com | www.573290.com | www.286058.com | www.993927.com | www.634029.com | 彩天下www.196016.com | www.903691.com | www.85221.cc | www.3549.vip | 鸿利彩票www.588088.com | 119926.com | www.812051.com | www.442542.com | 爱彩乐www.347918.com | www.28636.cc | www.337.cm | 775130.com | www.706928.com | 62996.com | www.898155.com | www.199424.com | www.34851.com | www.95126.com | www.964618.com | www.699718.com | www.353319.com | www.582208.com | www.123430.cc | www.241946.com | www.5949.org | www.246229.com | 495272.com | www.884743.com | www.54io.com | 699603.com | www.052855.com | www.053239.com | www.3312.com | www.94vk.com | 500彩票网www.745955.com | www.3803.vip | www.980374.com | www.358657.com | www.163194.com | www.953145.com | www.102458.com | www.886.cm | www.150133.com | www.42905.com | www.89499.cc | www.220325.com | www.51870.cc | www.172199.com | www.222779.com | www.99832.cc | www.08zi.com | www.093293.com | www.107012.com | www.402983.com | www.484228.com | www.022168.com | www.91pz.cc | www.2005.cc | www.0550.com | www.cp017.com | www.482895.com | www.9935.net | www.79ws.com | 192967.com | 大玩家彩票www.316083.com | www.645353.com | www.md79.com | 902118.cc | www.172159.com | www.07zm.com | 266901.com | www.857716.com | www.519899.com | www.44rq.com | www.314423.com | www.7lg.com | www.179020.com | www.7071.net | www.40948.com | www.03so.com | 9763.biz | www.590337.com | www.217461.com | www.9695.org | 825172.com | www.844789.com | www.398097.com | www.237221.com | www.1784.cm | 032586.com | 941059.com | www.658444.com | www.133333.com | www.16263.com | 体彩网www.3890a.com | www.881907.com | www.362995.com | www.41608.com | 六福彩票www.66ffs.com | www.872469.com | www.349918.com | www.233254.com | www.856521.com | www.6792.in | www.065195.com | www.58eo.com | www.6664.org | www.354488.com | www.34049.com | www.950929.com | www.0627.cn | www.009419.com | www.9178.in | www.pm33.com | 567439.com | www.900058.com | www.77074.com | www.13yk.com | www.538939.com | www.1qb.cc | 574872.com | www.727625.com | www.376520.com | www.75975.com | www.4py.com | www.554116.com | www.115663.com | www.283750.com | www.221484.com | www.188400.com | www.7488.in | www.23772.cc | www.mm81.com | 993457.com | www.681642.com | www.118041.com | www.653018.com | www.595319.com | 347005.com | www.54cl.com | www.019905.com | www.532.net | www.102111.com | www.998.cn | www.57ks.com | 064343.com | 818948.com | www.137593.com | www.988811.cc | 625319.com | www.924322.com | www.401258.com | www.061736.com | www.97ir.com | www.cc37.com | 648592.com | www.704828.com | www.268969.com | www.00557.cc | 500彩票www.904857.com | www.6438.cm | www.9521.biz | 875010.com | www.912985.com | www.336957.com | www.0413.site | www.mk73.com | 731980.com | www.024848.com | 73391.com | www.880559.com | www.693713.com | www.385358.com | www.616123.com | 553688.com | www.581690.com | www.53ow.com | www.474251.com | www.023136.com | www.877792.com | www.614.me | www.131605.com | www.226503.com | 908955.com | www.20ts.com | www.190789.com | www.079896.com | www.1280.vip | www.199564.com | www.358867.com | 678224.com | www.425941.com | 683087.com | www.952963.com | www.cai1177.com | www.025611.com | www.yg5.cc | www.973941.com | www.025445.com | www.0532.org | 403600.com | www.682943.com | www.150918.com | www.476807.com | www.850396.com | 94sg.com | 069563.com | www.865896.com | www.370229.com | www.104041.com | www.72jv.com | 亿彩堂www.87668f.com | www.992298.com | www.605113.com | 369496.com | www.684355.com | www.54818.com | 大赢家彩票平台www.082710.com | www.710130.com | www.76rd.com | 664980.com | www.675310.com | www.092270.com | www.455456.com | www.789669.com | k3k3彩票www.602985.com | 680797.com | www.22823.cc | www.141819.com | www.8479.vip | www.268560.com | www.74679.com | www.458.me | www.bh5.com | www.il33.com | www.03cu.com | 974588.com | www.716689.com | www.633602.com | 358343.com | www.4411.online | 843588.com | www.755399.com | www.181874.com | www.348103.com | 907585.com | www.44st.com | www.374331.com | www.173577.com | www.452070.com | www.019726.com | www.54vm.com | www.13609.com | 788989.com | www.354191.com | www.3470.vip | 彩69www.022197.com | www.699085.com | www.732958.com | www.226080.com | www.596107.com | www.4146.com | www.290034.com | www.092858.com | www.711871.com | www.50792.com | www.948242.com | www.958646.com | www.305856.com | www.277272.com | www.79uz.com | www.564122.com | www.717092.com | www.71hk.com | 186384.com | 214752.com | www.405966.com | www.874946.com | www.37229.cc | 13e彩票www.820535.com | 681476.com | www.552049.com | www.940213.com | www.072094.com | www.6901.vip | www.536408.com | www.953443.com | www.473323.com | www.693503.com | 954729.com | www.909144.com | 大赢家彩票网www.178211.com | 854816.com | www.869892.com | www.681022.com | www.yg19.com | www.757926.com | www.402185.com | www.397851.com | 399629.com | www.898339.com | www.858588.cc | 博友彩www.369908.com | www.86ir.com | 260824.com | 844012.com | www.as69.com | www.7916.org | 63ji.com | www.142037.com | www.035227.com | www.98999.com | www.539671.com | 674546.com | 586334.com | www.980647.com | www.366571.com | www.34897.com | www.f25.shop | www.017289.com | www.9343.vip | www.87yu.com | www.tl13.com | www.24ur.com | www.145330.com | www.931338.com | 杏彩www.00840s.com | www.493652.com | www.061119.com | www.64342.com | www.557118.com | www.908944.com | www.590717.com | 645256.com | www.747388.com | www.970606.com | www.044077.com | www.587868.com | www.560451.cc | www.22240.com | www.444269.com | www.39qz.com | www.wz59.cc | www.in92.com | 2371.biz | www.mu32.com | 盈发彩票www.99yfa.com | www.29yo.com | 367927.com | www.rh43.com | 997324.com | 949758.com | www.604769.com | 彩票坊www.022ah.cc | www.268.cc | 954070.com | 40zt.com | www.874188.com | www.639577.com | www.723492.com | www.974696.com | www.313079.com | www.86lg.com | 374904.com | www.233385.com | www.565596.com | 福利彩票www.78700k.com | www.900150.com | www.655620.com | 472686.com | www.778290.com | www.242415.com | www.023814.com | www.3yh.cc | cai1414.com | www.907028.com | www.350468.com | www.96163.cc | www.655546.com | www.699516.com | www.859107.com | www.651354.com | www.538281.com | www.8447.pw | www.021311.com | www.611710.com | www.712582.com | www.092026.com | www.7717.org | 801239.com | www.599502.com | www.310348.com | www.284028.com | www.432115.com | www.962216.com | 2691.xyz | www.981929.com | www.567120.com | www.522987.com | www.586713.com | www.928628.com | www.525453.com | www.076424.com | www.745933.com | www.157035.com | www.73573.cc | 天天彩票www.205882.com | www.431111.cc | www.78397.cc | www.79281.com | www.09692.com | www.6724.cc | 319505.com | www.720528.com | 629131.com | www.639728.com | www.693357.com | www.223954.com | 043225.com | www.836127.com | www.335960.com | www.63712.cc | www.699.cm | 522942.com | www.495312.com | www.789641.com | www.138247.com | www.835111.cc | www.315116.com | www.63991.com | 884034.com | www.880664.com | www.382014.com | www.72700.cc | www.47jv.com | 073770.com | www.543699.com | www.36426.com | www.76988.com | www.da52.com | www.955648.com | www.394244.com | 954256.com | www.315664.com | 029726.com | www.665483.com | 265789.cc | www.862142.com | www.314514.com | www.5642.org | 387314.com | www.759837.com | www.232617.com | www.09fh.com | www.456749.com | www.920913.com | www.363549.com | 081332.com | www.815981.com | www.522820.com | www.119976.com | www.998968.com | www.436969.com | www.3659.me | www.vc86.com | www.89840.com | www.cai3966.com | www.722239.com | 363267.com | 668825.cc | www.f20.net | 951341.com | www.199069.com | www.478.cc | 148868.com | nh35.com | www.kj72.cc | www.gn02.com | 多乐彩票www.422626.com | www.915280.com | www.948079.com | www.856385.com | www.871984.com | www.251330.com | www.299326.com | www.031640.com | www.778407.com | www.796306.com | www.962804.com | 551812.com | www.894773.com | www.870024.com | 699041.com | www.072750.com | www.997922.com | www.490548.com | 快彩www.81678r.com | www.807700.com | www.888565.com | www.398233.com | www.140655.com | www.374102.com | www.675515.com | www.501872.com | www.12ye.cc | www.uh3.cc | 947675.com | www.625038.com | www.806482.com | www.154959.com | www.276198.com | www.1515.net | www.1745.vip | www.020445.com | www.845113.com | 843061.com | www.745839.com | 675960.com | 324273.com | www.630442.com | www.239318.com | 13e彩票www.816142.com | 网易彩票www.077wy.com | www.0976.bid | www.601654.com | 40ja.com | www.2ha.com | www.cp2678.com | 018905.com | www.4555.xyz | 160816.com | www.875422.com | 941661.com | www.692570.com | www.277237.com | www.75rx.com | www.35316.cc | 082685.com | www.245691.com | 714014.com | www.590093.com | www.020670.com | www.608087.com | www.022964.com | www.5024.com | 534418.com | www.659051.com | www.539918.com | www.618856.com | www.549909.com | www.009433.com | 791031.com | www.cp146.com | www.996146.com | www.d32.cn | www.981850.com | www.286575.com | www.357120.com | www.53250.com | www.863.hk | www.cai5922.com | cp2031.com | www.xm91.com | 117419.com | www.766121.com | www.175288.com | www.82735.com | www.cai1950.com | www.899066.com | www.273526.com | 217456.com | www.432423.com | www.0376.site | www.039073.com | www.26391.com | 365473.cc | www.08fx.com | www.768287.com | www.979130.com | www.129335.com | www.715556.com | www.131170.com | www.946607.com | www.280694.com | www.335849.com | www.9535.online | www.446756.com | www.660904.com | www.546510.com | 980088.com | www.32bs.com | 358020.com | www.568482.com | www.79216.com | 794019.com | www.781171.com | www.152637.com | www.zn14.com | 994687.com | www.580357.com | www.56465.com | 387759.com | www.432546.com | www.55go.cc | 597876.com | www.699010.com | www.057553.com | www.bs46.com | www.807116.com | www.176603.com | www.567846.com | 290028.com | www.08509.com | 936967.com | www.915693.com | www.247368.com | www.478117.com | 372260.com | www.740513.com | 881704.com | www.801200.com | www.650877.com | yl71.com | www.440053.com | www.136076.com | www.95150.com | www.451636.com | 949856.com | www.718676.com | www.828482.com | 好彩头www.51331h.com | www.874257.com | www.938768.com | 大玩家彩票www.9478z.com | www.882928.com | 500彩票www.003851.com | 133394.com | www.799929.com | www.669227.com | www.24pj.cc | www.873870.com | www.49883.com | www.cd90.com | www.959763.com | 854883.com | www.4192.cn | www.017850.com | www.z60.top | www.974314.com | www.337100.cc | www.3060.top | 766579.com | 259563.com | www.878433.com | www.820073.com | www.550.tv | www.656797.com | www.938246.com | www.513424.com | www.28493.com | www.02.link | www.37618.com | www.p66.top | 916511.com | www.394951.com | www.9700.vip | www.108885.com | www.225940.com | www.68th.com | 637690.com | www.668480.com | www.09726.com | 084189.com | www.328519.com | www.525753.com | www.21nv.com | www.335460.com | www.903326.com | www.313208.com | www.4793.vip | www.9395.xyz | 593589.com | www.930350.com | www.214989.com | www.7601.me | 033592.com | www.85ao.com | 387788.com | www.575329.com | www.30239.com | www.bl98.com | www.865530.com | www.175117.com | www.b10.mobi | www.943401.com | www.254626.com | www.23lg.com | www.950545.com | www.262396.com | www.41qq.com | 096841.com | www.508907.com | www.4223.biz | 6394.biz | www.817995.com | www.118584.com | www.jt8.com | www.810863.com | www.098523.com | www.an80.cc | www.778523.com | www.091122.com | 聚彩网www.290282.com | www.792621.com | www.318834.com | www.121.live | www.977125.com | www.263752.com | www.17rm.com | www.938342.com | www.227852.com | www.22du.com | www.942668.com | www.219618.com | www.h19.me | www.939833.com | www.327917.com | www.18jy.com | www.976173.com | www.318621.com | www.20ku.com | www.982625.com | www.392074.com | www.5569.me | www.cp3316.com | www.771043.com | www.099466.com | www.di55.com | www.781922.com | www.237436.com | www.1905.com | 297000.com | www.683686.com | www.037598.com | www.039694.com | www.cr6.com | 253236.com | www.465772.com | www.44yf.com | www.855923.com | www.593881.com | www.550115.com | www.200298.com | www.rq87.com | www.857333.com | www.88583.cc | 604508.com | www.603998.com | www.08283.cc | 947927.com | www.446722.com | www.07575.cc | 971659.com | www.382839.com | www.80ly.com | 067039.com | www.287090.com | www.v74.club | www.839016.com | www.076798.com | 体彩网www.3890z.com | www.697996.com | www.031030.com | 易彩网www.12455m.com | www.608175.com | www.9966.pw | 500万彩票www.39500i.com | www.652707.com | www.28653.cc | qg21.com | www.204582.com | www.fp12.com | www.747572.com | www.024218.com | 351276.com | www.555420.com | www.7375.top | 258705.com | www.324327.com | www.77.me | www.870696.com | www.060084.com | www.2yb.com | www.876839.com | www.096080.com | www.08bh.com | www.863190.com | www.161608.com | www.058272.com | 0601.cc | www.574064.com | www.7364.org | 598039.com | www.289904.com | www.71pj.cc | www.919567.com | www.130509.com | 818合彩www.www.9889hc.com | 855828.com | www.283622.com | www.32rz.com | www.915856.com | www.154896.com | 808279.com | www.449249.com | 590275.com | www.637203.com | www.951849.com | www.250305.com | www.58yc.com | www.955799.com | www.654969.com | www.68972.cc | www.021.cc | www.8870.loan | www.yv86.com | www.982099.cc | www.118486.com | 919286.com | www.76tf.com | www.902632.com | www.207095.com | 345585.com | www.xy52.cc | www.931772.com | www.314001.com | www.88327.cc | www.68er.com | 078987.com | www.an21.com | 购彩在线www.66332r.com | www.718814.com | www.563.cm | ul42.com | www.759411.com | www.tm2.com | www.318639.cc | www.61rw.com | www.178031.com | www.73jv.com | www.352527.com | www.17890.com | 978.net | www.760917.com | www.984928.com | www.226183.com | www.cp30.com | www.54gt.com | www.914752.com | www.459300.com | www.45ls.com | www.814664.com | www.157626.com | www.071618.com | 亿彩堂www.87668g.com | www.855126.com | www.871964.com | www.541154.com | www.066033.com | www.798508.com | 470996.com | www.738834.com | 梦想彩票www.33112h.com | www.691370.com | www.62261.com | 338436.com | www.382952.com | www.83vp.com | www.812922.com | www.438888.com | 002229.cc | www.649853.com | www.fo09.com | www.925556.com | www.887231.com | www.354608.com | www.81al.com | www.959897.com | www.055140.com | 076722.com | www.447348.com | www.5764.vip | www.983724.com | www.198491.com | www.28la.com | www.967441.com | www.189908.com | 802566.com | www.551221.com | www.021891.com | 331028.com | www.215931.com | www.p92.com | www.14bt.com | www.32078.com | www.c07.cm | www.808085.com | www.94187.com | 669440.com | www.567343.com | www.151.hk | 954679.com | www.507326.com | www.9232.biz | 897677.com | www.ji26.com | 456289.com | www.qb96.com | www.62711.com | 682946.com | www.593831.com | www.8202.top | 061850.com | www.415408.com | www.622360.com | www.736725.com | www.713311.com | www.662032.com | www.574156.com | www.272194.com | www.445088.com | www.1374.vip | www.3884.biz | www.921733.com | www.064415.com | 386920.com | www.661654.com | www.555833.com | www.65756.com | 954302.com | www.575582.com | www.5921.xyz | www.095132.com | www.048747.com | www.101917.com | 872602.com | www.379301.com | www.132698.com | www.759160.com | www.005698.com | www.bw1.cc | www.766496.com | www.830424.com | www.056203.com | www.on67.com | www.757089.com | www.222387.com | www.306452.com | www.40zt.com | www.825187.com | www.gy08.com | www.mh36.com | www.964304.com | www.915728.com | www.701133.com | www.089046.com | www.317970.com | 众彩www.348116.com | 028627.com | www.5091.biz | 358234.com | 390200.com | www.455667.com | www.792583.com | 026155.com | www.693198.com | www.77627.com | www.133339.com | 0280.net | www.015308.com | 大赢家彩票www.526411.com | www.809282.com | www.884590.com | www.680567.cc | www.143129.com | www.on79.com | 464618.com | www.808265.com | www.041815.com | www.cp698.com | www.882867.com | www.045491.com | 267781.com | www.514079.com | www.564.cm | www.932009.com | www.101554.com | 356055.com | www.577953.com | www.516918.com | www.17662.cc | www.kf13.com | www.960540.com | www.419332.com | www.98zi.com | 63608.com | www.5041234.com | www.295575.com | www.070821.com | 990638.com | www.583882.com | www.631535.com | www.663377.com | www.996913.com | www.057993.com | www.649069.com | www.75cv.com | www.896049.com | www.088145.com | www.974930.com | www.jc54.com | 951782.com | www.900118.com | www.062967.com | 526560.com | www.631719.com | www.5249.com | www.46370.cc | 448163.com | www.566930.com | www.1380.cc | 537523.com | www.459876.com | www.987075.com | www.362935.com | www.21uy.com | www.913082.com | www.025681.com | 亿万彩票www.234397.com | www.787098.com | www.574985.com | www.9936.loan | www.5920.tv | www.3572.top | www.705354.com | www.53293.cc | 714238.com | www.354401.com | www.177222.com | www.506988.cc | 333168.cc | www.693076.com | www.016215.com | 418503.cc | www.543873.com | www.0220.site | 069876.com | www.cp126.cc | www.672056.com | www.502749.com | www.6718.top | 吉利彩票www.80065z.com | www.681476.com | 911978.com | www.220950.cc | www.55it.cc | www.919536.com | www.102348.com | 820232.com | www.629385.com | www.781470.com | www.54481.com | www.pj97.cc | www.239512.com | www.859492.com | 893095.com | 16098.com | www.277030.com | www.2912.com | www.040883.com | www.ca67.com | www.989518.com | 876038.com | www.686898.com | www.744456.com | www.677684.com | www.48236.com | www.704391.com | 027927.com | www.318105.com | 500彩票www.550207.com | www.71el.com | www.965271.com | www.108790.com | 277141.com | www.562142.com | www.5333.pw | 790713.com | www.279328.com | www.ch78.com | www.710797.com | www.13638.cc | www.999558.com | www.154506.com | www.ok01.cc | 913788.com | www.266867.com | www.fv02.com | www.835988.com | www.85258.cc | 168376.com | www.522376.com | www.0798.bid | www.942325.com | www.098634.com | 296905.com | www.625682.com | www.8716.loan | www.988660.com | www.132211.com | 760497.com | www.553000.com | www.896.website | www.955958.com | www.122296.com | 62291.com | www.552730.com | www.0818.cn | www.927967.com | www.2065.net | PK彩票www.8499p.com | www.876611.com |