Cook Brandoch D
Department of Surgery, Weill Cornell Medical College, New York, NY 10065, USA.
Front Biol (Beijing). 2014 Oct;9(5):339-346. doi: 10.1007/s11515-014-1328-9.
The onset of hematopoiesis in mammals is defined by generation of primitive erythrocytes and macrophage progenitors in embryonic yolk sac. Laboratories have met the challenge of transient and swiftly changing specification events from ventral mesoderm through multipotent progenitors and maturing lineage-restricted hematopoietic subtypes, by developing powerful experimental models to interrogate hematopoietic ontogeny. Most importantly, studies of differentiating embryonic stem cell derivatives in embryoid body and stromal coculture systems have identified crucial roles for transcription factor networks (e.g. , , ) and signaling pathways (e.g. BMP, VEGF, WNT) in controlling stem and progenitor cell output. These and other relevant pathways have pleiotropic biological effects, and are often associated with early embryonic lethality in knockout mice. Further refinement in subsequent studies has allowed conditional expression of key regulatory genes, and isolation of progenitors via cell surface markers (e.g. FLK1) and reporter-tagged constructs, with the purpose of measuring their primitive and definitive hematopoietic potential. These observations continue to inform attempts to direct the differentiation, and augment the expansion, of progenitors in human cell culture systems that may prove useful in cell replacement therapies for hematopoietic deficiencies. The purpose of this review is to survey the extant literature on the use of differentiating murine embryonic stem cells in culture to model the developmental process of yolk sac hematopoiesis.
哺乳动物造血作用的起始是由胚胎卵黄囊中原始红细胞和巨噬细胞祖细胞的产生来定义的。各实验室通过开发强大的实验模型来探究造血个体发生，从而应对了从腹侧中胚层经多能祖细胞到成熟的谱系受限造血亚型这一短暂且迅速变化的特化事件所带来的挑战。最重要的是，对胚状体和基质共培养系统中分化的胚胎干细胞衍生物的研究已经确定了转录因子网络（例如……）和信号通路（例如骨形态发生蛋白、血管内皮生长因子、WNT）在控制干细胞和祖细胞输出方面的关键作用。这些以及其他相关通路具有多效性生物学效应，并且在基因敲除小鼠中常常与早期胚胎致死性相关。后续研究的进一步细化使得关键调控基因能够条件性表达，并且通过细胞表面标志物（例如FLK1）和报告基因标记构建体分离祖细胞，目的是测量它们的原始和确定造血潜能。这些观察结果继续为指导人类细胞培养系统中祖细胞的分化和增强其扩增的尝试提供信息，这可能在造血缺陷的细胞替代疗法中证明是有用的。本综述的目的是调查关于在培养中使用分化的小鼠胚胎干细胞来模拟卵黄囊造血发育过程的现有文献。
