Laboratory for Stem Cell Biology, and Laboratory for Early Embryogenesis, Center for Developmental Biology, RIKEN Kobe Institute, Kobe, Hyogo 650-0047, Japan.
Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4515-20. doi: 10.1073/pnas.1115828109. Epub 2012 Mar 5.
Several lines of evidence suggest that the adult hematopoietic system has multiple developmental origins, but the ontogenic relationship between nascent hematopoietic populations under this scheme is poorly understood. In an alternative theory, the earliest definitive blood precursors arise from a single anatomical location, which constitutes the cellular source for subsequent hematopoietic populations. To deconvolute hematopoietic ontogeny, we designed an embryo-rescue system in which the key hematopoietic factor Runx1 is reactivated in Runx1-null conceptuses at specific developmental stages. Using complementary in vivo and ex vivo approaches, we provide evidence that definitive hematopoiesis and adult-type hematopoietic stem cells originate predominantly in the nascent extraembryonic mesoderm. Our data also suggest that other anatomical sites that have been proposed to be sources of the definitive hematopoietic hierarchy are unlikely to play a substantial role in de novo blood generation.
有几条证据表明，成人造血系统具有多种发育起源，但在这种方案下，新生造血群体之间的个体发生关系还不太清楚。在另一种理论中，最早的确定性血液前体来自于一个单一的解剖位置，该位置构成了随后造血群体的细胞来源。为了解开造血个体发生的难题，我们设计了一种胚胎挽救系统，在该系统中，关键的造血因子 Runx1 在特定的发育阶段在 Runx1 缺失的胚胎中被重新激活。我们使用互补的体内和体外方法，提供了证据表明，确定性造血和成人型造血干细胞主要来源于新生的胚胎外中胚层。我们的数据还表明，其他被认为是确定性造血层次结构来源的解剖部位不太可能在新的血液生成中发挥重要作用。
