Single-lineage transcriptome analysis reveals key regulatory pathways in primitive erythroid progenitors in the mouse embryo
Single-lineage transcriptome analysis reveals key regulatory pathways in primitive erythroid progenitors in the mouse embryo
复制标题
DOI：
10.1182/blood-2010-10-313676
复制
发表时间：
2011-05-05
期刊：
影响因子：
20.3
通讯作者：
Baron, Margaret H.
中科院分区：
文献类型：
--
作者：
Isern, Joan;He, Zhiyong;Baron, Margaret H.
原始红系 (EryP) 祖细胞是原肠胚形成晚期中胚层特异的第一种细胞类型。我们使用转基因报告基因对发育中的小鼠胚胎中最早的血液祖细胞及其后代进行成像和纯化。 EryP 祖细胞在循环开始前立即在卵黄囊中表现出显着的增殖能力，此时这些细胞几乎占胚胎所有细胞的一半。从胚胎第 7.5 天到第 2.5 天，每隔 24 小时生成一次全局表达谱，揭示了转录物多样性的 2 个突变，分别与 EryPs 进入循环以及它们的晚期成熟和去核相一致。这些变化与关键调节因子的表达同时发生。旨在测试这些数据预测的实验表明，Wnt 信号通路在 EryP 祖细胞中活跃，该祖细胞表现出有氧糖酵解特征，并且其数量受到转化生长因子-β 1 和缺氧的调节。这是在胚胎分化过程中为胚胎的单一造血谱系组装的第一个转录组。 （血。2011；117(18):4924-4934）
Primitive erythroid (EryP) progenitors are the first cell type specified from the mesoderm late in gastrulation. We used a transgenic reporter to image and purify the earliest blood progenitors and their descendants from developing mouse embryos. EryP progenitors exhibited remarkable proliferative capacity in the yolk sac immediately before the onset of circulation, when these cells comprise nearly half of all cells of the embryo. Global expression profiles generated at 24-hour intervals from embryonic day 7.5 through 2.5 revealed 2 abrupt changes in transcript diversity that coincided with the entry of EryPs into the circulation and with their late maturation and enucleation, respectively. These changes were paralleled by the expression of critical regulatory factors. Experiments designed to test predictions from these data demonstrated that the Wnt-signaling pathway is active in EryP progenitors, which display an aerobic glycolytic profile and the numbers of which are regulated by transforming growth factor-beta 1 and hypoxia. This is the first transcriptome assembled for a single hematopoietic lineage of the embryo over the course of its differentiation. (Blood. 2011;117(18):4924-4934)