Definitive hematopoietic stem cells minimally contribute to embryonic hematopoiesis

Cell Rep. 2021 Sep 14;36(11):109703. doi: 10.1016/j.celrep.2021.109703.


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.

Keywords: developmental hematopoiesis; differentiation; hematopoietic progenitors; hematopoietic stem cell; lineage tracing; scRNA-seq; self-renewal; zebrafish.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation
  • Cell Lineage
  • Cell Self Renewal
  • Embryonic Development / genetics
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Flow Cytometry
  • Hematopoiesis*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Mice
  • Single-Cell Analysis
  • Transcriptome
  • Zebrafish