RT Journal Article SR Electronic T1 Definitive Hematopoietic Stem Cells Minimally Contribute to Embryonic Hematopoiesis JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.05.02.442359 DO 10.1101/2021.05.02.442359 A1 Bianca A Ulloa A1 Samima S Habbsa A1 Kathryn S. Potts A1 Alana Lewis A1 Mia McKinstry A1 Sara G. Payne A1 Julio Flores A1 Anastasia Nizhnik A1 Maria Feliz Norberto A1 Christian Mosimann A1 Teresa V Bowman YR 2021 UL http://biorxiv.org/content/early/2021/05/03/2021.05.02.442359.abstract AB Hematopoietic stem cells (HSCs) are rare cells that arise in the embryo and sustain adult hematopoiesis. Although the functional potential of nascent HSCs is detectable by transplantation, their native contribution during development is unknown, in part due to the overlapping genesis and marker gene expression with other embryonic blood progenitors. Using single cell transcriptomics, we defined gene signatures that distinguish nascent HSCs from embryonic blood progenitors. Applying a new lineage tracing approach, we selectively tracked HSC output in situ and discovered significantly delayed lymphomyeloid contribution. Using a novel inducible HSC injury model, we demonstrated a negligible impact on larval lymphomyelopoiesis following HSC depletion. HSCs are not merely dormant at this developmental stage as they showed robust regeneration after injury. Combined, our findings illuminate that nascent HSCs self-renew but display differentiation latency, while HSC-independent embryonic progenitors sustain developmental hematopoiesis. Understanding the differences among embryonic HSC and progenitor populations will guide improved de novo generation and expansion of functional HSCs.Competing Interest StatementThe authors have declared no competing interest.