Induction of multipotential hematopoietic progenitors from human pluripotent stem cells via respecification of lineage-restricted precursors.
Induction of multipotential hematopoietic progenitors from human pluripotent stem cells via respecification of lineage-restricted precursors.
复制标题
DOI：
10.1016/j.stem.2013.09.002
复制
发表时间：
2013-10-03
期刊：
影响因子：
23.9
通讯作者：
Daley, George Q.
中科院分区：
文献类型：
--
作者：
Doulatov, Sergei;Vo, Linda T.;Chou, Stephanie S.;Kim, Peter G.;Arora, Natasha;Li, Hu;Hadland, Brandon K.;Bernstein, Irwin D.;Collins, James J.;Zon, Leonard I.;Daley, George Q.
人多能干细胞（hPSC）代表了用于疾病建模、药物筛选和细胞疗法的患者特异性细胞的有希望的来源。然而，无法获得可移植的人造血干细胞和祖细胞（HSPC）限制了其在体外测定的表征。我们报告了一种策略，重新指定谱系限制的CD34+CD45+骨髓前体来源于hPSC的多谱系祖细胞，可以在体外扩增和体内移植。HOXA 9、ERG和RORA在体外赋予自我更新和多谱系潜能，并维持原始的CD34+CD38−细胞。通过移植筛选细胞揭示了两个额外的因子，SOX 4和MYB，需要植入。指定的所有五个因素的祖细胞引起了可重现的短期移植与髓系和红系。红系前体在体内经历血红蛋白转换，沉默胚胎和激活成人珠蛋白表达。我们的组合筛选方法建立了一个策略，从人类多能细胞获得转录因子介导的造血祖细胞植入。
Human pluripotent stem cells (hPSCs) represent a promising source of patient-specific cells for disease modeling, drug screens, and cellular therapies. However, the inability to derive engraftable human hematopoietic stem and progenitor (HSPCs) has limited their characterization to in vitro assays. We report a strategy to re-specify lineage-restricted CD34+CD45+ myeloid precursors derived from hPSCs into multilineage progenitors that can be expanded in vitro and engraft in vivo. HOXA9, ERG, and RORA conferred self-renewal and multilineage potential in vitro and maintained primitive CD34+CD38− cells. Screening cells via transplantation revealed that two additional factors, SOX4 and MYB, were required for engraftment. Progenitors specified with all five factors gave rise to reproducible short-term engraftment with myeloid and erythroid lineages. Erythroid precursors underwent hemoglobin switching in vivo, silencing embryonic and activating adult globin expression. Our combinatorial screening approach establishes a strategy for obtaining transcription factor-mediated engraftment of blood progenitors from human pluripotent cells.
登录
查看更多内容
影响因子：
30.5
作者：
Laurenti E;Doulatov S;Zandi S;Plumb I;Chen J;April C;Fan JB;Dick JE
通讯作者：
Dick JE
影响因子：
4
作者：
Dias, Jessica;Gumenyuk, Marina;Slukvin, Igor I.
通讯作者：
Slukvin, Igor I.
影响因子：
82.9
作者：
Eppert, Kolja;Takenaka, Katsuto;Dick, John E.
通讯作者：
Dick, John E.
影响因子：
82.9
作者：
Amsellem, S;Pflumio, F;Fichelson, S
通讯作者：
Fichelson, S
影响因子：
20.3
作者：
Huang, Yongsheng;Sitwala, Kajal;Hess, Jay L.
通讯作者：
Hess, Jay L.