RRC ID 81149
Author Morino-Koga S, Tsuruda M, Zhao X, Oshiro S, Yokomizo T, Yamane M, Tanigawa S, Miike K, Usuki S, Yasunaga KI, Nishinakamura R, Suda T, Ogawa M.
Title Transition of signal requirement in hematopoietic stem cell development from hemogenic endothelial cells.
Journal Proc Natl Acad Sci U S A
Abstract Hematopoietic stem cells (HSCs) develop from hemogenic endothelial cells (HECs) in vivo during mouse embryogenesis. When cultured in vitro, cells from the embryo phenotypically defined as pre-HSC-I and pre-HSC-II have the potential to differentiate into HSCs. However, minimal factors required for HSC induction from HECs have not yet been determined. In this study, we demonstrated that stem cell factor (SCF) and thrombopoietin (TPO) induced engrafting HSCs from embryonic day (E) 11.5 pre-HSC-I in a serum-free and feeder-free culture condition. In contrast, E10.5 pre-HSC-I and HECs required an endothelial cell layer in addition to SCF and TPO to differentiate into HSCs. A single-cell RNA sequencing analysis of E10.5 to 11.5 dorsal aortae with surrounding tissues and fetal livers detected TPO expression confined in hepatoblasts, while SCF was expressed in various tissues, including endothelial cells and hepatoblasts. Our results suggest a transition of signal requirement during HSC development from HECs. The differentiation of E10.5 HECs to E11.5 pre-HSC-I in the aorta-gonad-mesonephros region depends on SCF and endothelial cell-derived factors. Subsequently, SCF and TPO drive the differentiation of E11.5 pre-HSC-I to pre-HSC-II/HSCs in the fetal liver. The culture system established in this study provides a beneficial tool for exploring the molecular mechanisms underlying the development of HSCs from HECs.
Volume 121(31)
Pages e2404193121
Published 2024-7-30
DOI 10.1073/pnas.2404193121
PMID 39042698
MeSH Animals Cell Differentiation* Embryo, Mammalian / cytology Embryo, Mammalian / metabolism Embryonic Development Endothelial Cells / cytology Endothelial Cells / metabolism Hemangioblasts* / cytology Hemangioblasts* / metabolism Hematopoiesis / physiology Hematopoietic Stem Cells* / cytology Hematopoietic Stem Cells* / metabolism Liver / cytology Liver / embryology Liver / metabolism Mice Signal Transduction Stem Cell Factor* / metabolism Thrombopoietin* / metabolism
Resource
Human and Animal Cells UV♀2(RCB1994)