Mouse Embryonic Head as a Site for Hematopoietic Stem Cell Development

Abstract

In the mouse embryo, the aorta-gonad-mesonephros (AGM) region is considered to be the sole location for intraembryonic emergence of hematopoietic stem cells (HSCs). Here we report that, in parallel to the AGM region, the E10.5-E11.5 mouse head harbors bona fide HSCs, as defined by long-term, high-level, multilineage reconstitution and self-renewal capacity in adult recipients, before HSCs enter the circulation. The presence of hemogenesis in the midgestation head is indicated by the appearance of intravascular cluster cells and the blood-forming capacity of a sorted endothelial cell population. In addition, lineage tracing via an inducible VE-cadherin-Cre transgene demonstrates the hemogenic capacity of head endothelium. Most importantly, a spatially restricted lineage labeling system reveals the physiological contribution of cerebrovascular endothelium to postnatal HSCs and multilineage hematopoiesis. We conclude that the mouse embryonic head is a previously unappreciated site for HSC emergence within the developing embryo.

Hemovascular Progenitors in the Kidney Require Sphingosine-1-Phosphate Receptor 1 for Vascular Development

“…A recent study showed that the mouse embryonic head also functions as a hemogenic organ to a similar extent as the AGM region, which suggests broader potential hemogenic areas in the mouse embryo; this is in agreement with previous studies showing that hemovasculogenesis also occurs in the head mesenchyme of early embryos. 13,26 The kidney is a major hemogenic organ in teleosts, such as zebrafish. Our results suggest that the mouse kidney also functions as a temporary hemogenic organ via hemovasculogenesis during early embryogenesis.…”

A short history of hemogenic endothelium

“…Combination of VECadh or CD31 with the hematopoietic markers CD41 [40][41][42][43], CD45 [44] and Ter119 [45] has been used to separate endothelial from hematopoietic cells (e.g. [38,[46][47][48]), and other identification strategies have also been employed e.g. [49] [50].…”

“…In this respect, two recent mouse studies give food for thought. Studies by Li and colleagues suggested that the head vasculature is a source of definitive HSCs [47]. Using in vitro and transplantation assays, hematopoietic potential was found to reside among Tie2 expressing cells isolated from the head.…”

miR-142-3p regulates the formation and differentiation of hematopoietic stem cells in vertebrates

“…To confirm the in vitro result, we performed a CFU-S (colony-forming unit-spleen) assay in vivo. As shown in Figure 7C, the number of CFU-S was increased in mice infused with duplex-treated AGM cells, whereas it was To determine whether miR-142-3p is also required for the differentiation of the T-lymphoid lineage in mouse, we performed a T-cell differentiation assay in vitro [35]. Dissociated cells from the AGM region were treated with the duplex or inhibitor for 5 h. Then, the sorted cKit + CD34 + cells were co-cultured with OP9-DL1 stromal cells and cytokines for 13 days, and the CD25 + CD44 + T-cell progenitors were quantified by fluorescenceactivated cell sorting (FACS).…”