In vivo generation of haematopoietic stem/progenitor cells from bone marrow-derived haemogenic endothelium

Nat Cell Biol. 2019 Nov;21(11):1334-1345. doi: 10.1038/s41556-019-0410-6. Epub 2019 Nov 4.


It is well established that haematopoietic stem and progenitor cells (HSPCs) are generated from a transient subset of specialized endothelial cells termed haemogenic, present in the yolk sac, placenta and aorta, through an endothelial-to-haematopoietic transition (EHT). HSPC generation via EHT is thought to be restricted to the early stages of development. By using experimental embryology and genetic approaches in birds and mice, respectively, we document here the discovery of a bone marrow haemogenic endothelium in the late fetus/young adult. These cells are capable of de novo producing a cohort of HSPCs in situ that harbour a very specific molecular signature close to that of aortic endothelial cells undergoing EHT or their immediate progenies, i.e., recently emerged HSPCs. Taken together, our results reveal that HSPCs can be generated de novo past embryonic stages. Understanding the molecular events controlling this production will be critical for devising innovative therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Aorta / cytology
  • Aorta / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism*
  • Cell Differentiation
  • Cell Lineage / genetics*
  • Chickens
  • Embryo, Mammalian
  • Embryo, Nonmammalian
  • Female
  • Fetus
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks
  • Hemangioblasts / cytology
  • Hemangioblasts / metabolism*
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Heterozygote
  • Homozygote
  • Male
  • Mice
  • Pregnancy
  • Yolk Sac / cytology
  • Yolk Sac / growth & development
  • Yolk Sac / metabolism