Runx1 is sufficient for blood cell formation from non-hemogenic endothelial cells in vivo only during early embryogenesis

Development. 2018 Jan 29;145(2):dev158162. doi: 10.1242/dev.158162.

Abstract

Hematopoietic cells differentiate during embryogenesis from a population of endothelial cells called hemogenic endothelium (HE) in a process called the endothelial-to-hematopoietic transition (EHT). The transcription factor Runx1 is required for EHT, but for how long and which endothelial cells are competent to respond to Runx1 are not known. Here, we show that the ability of Runx1 to induce EHT in non-hemogenic endothelial cells depends on the anatomical location of the cell and the developmental age of the conceptus. Ectopic expression of Runx1 in non-hemogenic endothelial cells between embryonic day (E) 7.5 and E8.5 promoted the formation of erythro-myeloid progenitors (EMPs) specifically in the yolk sac, the dorsal aorta and the heart. The increase in EMPs was accompanied by a higher frequency of HE cells able to differentiate into EMPs in vitro Expression of Runx1 just 1 day later (E8.5-E9.5) failed to induce the ectopic formation of EMPs. Therefore, endothelial cells, located in specific sites in the conceptus, have a short developmental window of competency during which they can respond to Runx1 and differentiate into blood cells.

Keywords: Embryo; Hematopoiesis; Hemogenic endothelium; Runx1.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Core Binding Factor Alpha 2 Subunit / metabolism*
  • Endothelial Cells / cytology*
  • Endothelial Cells / metabolism*
  • Female
  • Gene Expression Regulation, Developmental
  • Gestational Age
  • Hematopoiesis / genetics
  • Hematopoiesis / physiology*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Organ Specificity
  • Pregnancy
  • Yolk Sac / cytology
  • Yolk Sac / embryology
  • Yolk Sac / metabolism

Substances

  • Core Binding Factor Alpha 2 Subunit
  • Runx1 protein, mouse