Definitive hematopoietic stem cells minimally contribute to embryonic hematopoiesis

Bianca A. Ulloa, Samima S. Habbsa, Kathryn S. Potts, Alana Lewis, Mia McKinstry, Sara G. Payne, Julio C. Flores, Anastasia Nizhnik, Maria Feliz Norberto, Christian Mosimann, Teresa V. Bowman

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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 define gene signatures that distinguish nascent HSCs from embryonic blood progenitors. Applying a lineage-tracing approach to selectively track HSC output in situ, we find significantly delayed lymphomyeloid contribution. An inducible HSC injury model demonstrates 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 these differences could improve de novo generation and expansion of functional HSCs.

Original languageEnglish (US)
Article number109703
JournalCell Reports
Volume36
Issue number11
DOIs
StatePublished - Sep 14 2021

Keywords

  • developmental hematopoiesis
  • differentiation
  • hematopoietic progenitors
  • hematopoietic stem cell
  • lineage tracing
  • scRNA-seq
  • self-renewal
  • zebrafish

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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