Definitive Hematopoiesis in the Yolk Sac Emerges from Wnt-Responsive Hemogenic Endothelium Independently of Circulation and Arterial Identity
dc.contributor.author | Frame, Jenna M. | |
dc.contributor.author | Fegan, Katherine H. | |
dc.contributor.author | Conway, Simon J. | |
dc.contributor.author | McGrath, Kathleen E. | |
dc.contributor.author | Palis, James | |
dc.contributor.department | Department of Pediatrics, IU School of Medicine | en_US |
dc.date.accessioned | 2017-06-19T19:11:06Z | |
dc.date.available | 2017-06-19T19:11:06Z | |
dc.date.issued | 2016-02 | |
dc.description.abstract | Adult-repopulating hematopoietic stem cells (HSCs) emerge in low numbers in the midgestation mouse embryo from a subset of arterial endothelium, through an endothelial-to-hematopoietic transition. HSC-producing arterial hemogenic endothelium relies on the establishment of embryonic blood flow and arterial identity, and requires β-catenin signaling. Specified prior to and during the formation of these initial HSCs are thousands of yolk sac-derived erythro-myeloid progenitors (EMPs). EMPs ensure embryonic survival prior to the establishment of a permanent hematopoietic system, and provide subsets of long-lived tissue macrophages. While an endothelial origin for these HSC-independent definitive progenitors is also accepted, the spatial location and temporal output of yolk sac hemogenic endothelium over developmental time remain undefined. We performed a spatiotemporal analysis of EMP emergence, and document the morphological steps of the endothelial-to-hematopoietic transition. Emergence of rounded EMPs from polygonal clusters of Kit(+) cells initiates prior to the establishment of arborized arterial and venous vasculature in the yolk sac. Interestingly, Kit(+) polygonal clusters are detected in both arterial and venous vessels after remodeling. To determine whether there are similar mechanisms regulating the specification of EMPs with other angiogenic signals regulating adult-repopulating HSCs, we investigated the role of embryonic blood flow and Wnt/β-catenin signaling during EMP emergence. In embryos lacking a functional circulation, rounded Kit(+) EMPs still fully emerge from unremodeled yolk sac vasculature. In contrast, canonical Wnt signaling appears to be a common mechanism regulating hematopoietic emergence from hemogenic endothelium. These data illustrate the heterogeneity in hematopoietic output and spatiotemporal regulation of primary embryonic hemogenic endothelium. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Frame, J. M., Fegan, K. H., Conway, S. J., McGrath, K. E., & Palis, J. (2016). Definitive hematopoiesis in the yolk sac emerges from Wnt-responsive hemogenic endothelium independently of circulation and arterial identity. Stem Cells (Dayton, Ohio), 34(2), 431–444. http://doi.org/10.1002/stem.2213 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/13102 | |
dc.language.iso | en_US | en_US |
dc.publisher | Wiley | en_US |
dc.relation.isversionof | 10.1002/stem.2213 | en_US |
dc.relation.journal | Stem Cells | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Hematopoietic stem cells | en_US |
dc.subject | Hematopoiesis | en_US |
dc.subject | Hematopoietic progenitors | en_US |
dc.subject | Vascular development | en_US |
dc.subject | Endothelial cell | en_US |
dc.subject | Embryo | en_US |
dc.subject | Hemangioblast | en_US |
dc.title | Definitive Hematopoiesis in the Yolk Sac Emerges from Wnt-Responsive Hemogenic Endothelium Independently of Circulation and Arterial Identity | en_US |
dc.type | Article | en_US |