PT  - JOURNAL ARTICLE
AU  - Bianca A Ulloa
AU  - Samima S Habbsa
AU  - Kathryn S. Potts
AU  - Alana Lewis
AU  - Mia McKinstry
AU  - Sara G. Payne
AU  - Julio Flores
AU  - Anastasia Nizhnik
AU  - Maria Feliz Norberto
AU  - Christian Mosimann
AU  - Teresa V Bowman
TI  - Definitive Hematopoietic Stem Cells Minimally Contribute to Embryonic Hematopoiesis
AID  - 10.1101/2021.05.02.442359
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.02.442359
4099  - http://biorxiv.org/content/early/2021/05/03/2021.05.02.442359.short
4100  - http://biorxiv.org/content/early/2021/05/03/2021.05.02.442359.full
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.