RT Journal Article
SR Electronic
T1 Developmental trajectory of pre-hematopoietic stem cell formation from endothelium
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 848846
DO 10.1101/848846
A1 Qin Zhu
A1 Peng Gao
A1 Joanna Tober
A1 Laura Bennett
A1 Changya Chen
A1 Yasin Uzun
A1 Yan Li
A1 Melanie Mumau
A1 Wenbao Yu
A1 Bing He
A1 Nancy A. Speck
A1 Kai Tan
YR 2019
UL http://biorxiv.org/content/early/2019/11/27/848846.abstract
AB Hematopoietic stem and progenitor cells (HSPCs) differentiate from hemogenic endothelial (HE) cells through an endothelial to hematopoietic cell transition (EHT). Newly formed HSPCs accumulate in intra-arterial clusters (IACs) before colonizing the fetal liver. To examine the cell and molecular transitions during the EHT, and the heterogeneity of HSPCs within IACs, we profiled ∼37,000 cells from the caudal arteries of embryonic day 9.5 (E9.5) to E11.5 mouse embryos by single-cell transcriptome and chromatin accessibility sequencing. We identified an intermediate developmental stage prior to HE that we termed pre-HE, characterized by increased accessibility of chromatin enriched for SOX, FOX, GATA, and SMAD motifs. A developmental bottleneck separates pre-HE from HE, with RUNX1 dosage regulating the efficiency of the pre-HE to HE transition. Distinct developmental trajectories within IAC cells result in two populations of CD45+ HSPCs; an initial wave of lympho-myeloid-biased progenitors, followed by precursors of hematopoietic stem cells (pre-HSCs).