Symmetric self-renewal and dormancy define functional fetal liver hematopoietic stem cells at single cell resolution

Our study disclosed previously unrecognized heterogeneity in fetal liver (FL) hematopoietic stem cells (HSC), highlighting biosynthetic dormancy as a key to symmetric self-renewal of engraftable HSC and supports recent studies demonstrating distinct developmental origins for multipotent progenitors and HSC in definitive hematopoiesis. Overall design: single cell RNA-sequencing (10X Genomics platform) of murine E12 FL-derived cultured endothelial cells expressing mAkt (FL-EC) used as stroma to support HSC developemnt/expansion ex vivo; and murine E13.5 FL-derived FACS-isolated VEcadherin-/low,CD45+,Gra1-F4/80-,Sca1+,EPCR+ cells enriched for HSCs (primary cells and progeny following co-culture with FL-EC). Sample 4 also included CD11b-ESAM expression in sorting.