title: Hierarchical organization and early hematopoietic specification of the developing HSC lineage in the AGM region.
abstract: The aorta-gonad-mesonephros region plays an important role in hematopoietic stem cell (HSC) development during mouse embryogenesis. The vascular endothelial cadherin⁺ CD45⁺ (VE-cad⁺CD45⁺) population contains the major type of immature pre-HSCs capable of developing into long-term repopulating definitive HSCs. In this study, we developed a new coaggregation culture system, which supports maturation of a novel population of CD45-negative (VE-cad⁺CD45⁻CD41⁺) pre-HSCs into definitive HSCs. The appearance of these pre-HSCs precedes development of the VE-cad⁺CD45⁺ pre-HSCs (termed here type I and type II pre-HSCs, respectively), thus establishing a hierarchical directionality in the developing HSC lineage. By labeling the luminal surface of the dorsal aorta, we show that both type I and type II pre-HSCs are distributed broadly within the endothelial and subendothelial aortic layers, in contrast to mature definitive HSCs which localize to the aortic endothelial layer. In agreement with expression of CD41 in pre-HSCs, in vivo CD41-Cre-mediated genetic tagging occurs in embryonic pre-HSCs and persists in all lymphomyeloid lineages of the adult animal.
authors.affiliation: Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH9 3JQ, Scotland, UK.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Rybtsov
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Sobiesiak
authors.forename: Samir
authors.initials: S
authors.lastname: Taoudi
authors.forename: Céline
authors.initials: C
authors.lastname: Souilhol
authors.forename: Jordi
authors.initials: J
authors.lastname: Senserrich
authors.forename: Anna
authors.initials: A
authors.lastname: Liakhovitskaia
authors.forename: Andrejs
authors.initials: A
authors.lastname: Ivanovs
authors.forename: Jon
authors.initials: J
authors.lastname: Frampton
authors.forename: Suling
authors.initials: S
authors.lastname: Zhao
authors.forename: Alexander
authors.initials: A
authors.lastname: Medvinsky
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D019070:Cell Lineage; D002469:Cell Separation; D004730:Endothelium, Vascular / Q000166:cytology; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis*; D051379:Mice; D008957:Models, Genetic; D010641:Phenotype; D040201:Platelet Membrane Glycoprotein IIb / Q000096:biosynthesis; D019076:Transgenes
chemical_list: D015820:Cadherins; D040201:Platelet Membrane Glycoprotein IIb; D049452:Green Fluorescent Proteins; D017493:Leukocyte Common Antigens