In vivo repopulating activity emerges at the onset of hematopoietic specification during embryonic stem cell differentiation.
In vivo repopulating activity emerges at the onset of hematopoietic specification during embryonic stem cell differentiation.
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DOI：
10.1016/j.stemcr.2015.01.003
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发表时间：
2015-03-10
影响因子：
5.9
通讯作者：
Kouskoff, Valerie
中科院分区：
文献类型：
--
作者：
Pearson, Stella;Cuvertino, Sara;Fleury, Maud;Lacaud, Georges;Kouskoff, Valerie
从体外分化的胚胎干细胞产生体内再生造血细胞仍然是一个长期存在的挑战。迄今为止，造血移植主要通过异位转录因子的强制表达来实现。在这里，我们描述了无血清培养条件下，允许在体内再生造血细胞的异位表达的因素的情况下产生。我们发现，在造血规范的第一波内，在中胚层前体对血液程序的承诺后，立即产生重新填充活动。我们确定，这些祖细胞的形成是非常短暂的和精致的细胞因子环境敏感。我们的研究结果定义了造血再生活性首次在体外出现的精确分化阶段，并表明在胚胎干细胞分化过程中，所有造血程序同时从中胚层中解开，在没有限制每个谱系协调出现的线索的情况下，通常在胚胎发生过程中观察到。从无血清分化的ESC体内重建造血细胞重建活性在中胚层定型后立即产生体内重建祖细胞是非常短暂的体内重建祖细胞对细胞因子环境非常敏感。在这篇文章中，Kouskoff，Lacaud及其同事表明，无血清体外分化的胚胎干细胞产生体内重建造血祖细胞，再生活性在中胚层前体向血液程序定型后立即产生，并且这些祖细胞的形成是极其短暂的，并且对细胞因子环境非常敏感。
The generation of in vivo repopulating hematopoietic cells from in vitro differentiating embryonic stem cells has remained a long-standing challenge. To date, hematopoietic engraftment has mostly been achieved through the enforced expression of ectopic transcription factors. Here, we describe serum-free culture conditions that allow the generation of in vivo repopulating hematopoietic cells in the absence of ectopically expressed factors. We show that repopulating activity arises immediately upon the commitment of mesodermal precursors to the blood program, within the first wave of hematopoietic specification. We establish that the formation of these progenitors is extremely transient and exquisitely sensitive to the cytokine milieu. Our findings define the precise differentiating stage at which hematopoietic repopulating activity first appears in vitro, and suggest that during embryonic stem cell differentiation, all hematopoietic programs are unraveled simultaneously from the mesoderm in the absence of cues that restrict the coordinated emergence of each lineage as is normally observed during embryogenesis. In vivo repopulating hematopoietic cells from serum-free differentiated ESCs Repopulating activity arises immediately upon commitment of mesoderm In vivo repopulating progenitors are extremely transient In vivo repopulating progenitors are exquisitely sensitive to the cytokine milieu In this article, Kouskoff, Lacaud, and colleagues show that serum-free in vitro differentiated embryonic stem cells give rise to in vivo repopulating hematopoietic progenitors, that the repopulating activity arises immediately upon the commitment of mesodermal precursors to the blood program, and that the formation of these progenitors is extremely transient and exquisitely sensitive to the cytokine milieu.
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影响因子：
64.8
作者：
Kriks, Sonja;Shim, Jae-Won;Piao, Jinghua;Ganat, Yosif M.;Wakeman, Dustin R.;Xie, Zhong;Carrillo-Reid, Luis;Auyeung, Gordon;Antonacci, Chris;Buch, Amanda;Yang, Lichuan;Beal, M. Flint;Surmeier, D. James;Kordower, Jeffrey H.;Tabar, Viviane;Studer, Lorenz
通讯作者：
Studer, Lorenz
影响因子：
23.9
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.
通讯作者：
Daley, George Q.
影响因子：
5.3
作者：
KELLER, G;KENNEDY, M;WILES, MV
通讯作者：
WILES, MV
影响因子：
4.6
作者：
Ferkowicz, MJ;Starr, M;Yoder, MC
通讯作者：
Yoder, MC
影响因子：
20.3
作者：
Hole, N;Graham, GJ;Ansell, JD
通讯作者：
Ansell, JD