LYVE1 Marks the Divergence of Yolk Sac Definitive Hemogenic Endothelium from the Primitive Erythroid Lineage

Cell Rep. 2016 Nov 22;17(9):2286-2298. doi: 10.1016/j.celrep.2016.10.080.


The contribution of the different waves and sites of developmental hematopoiesis to fetal and adult blood production remains unclear. Here, we identify lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1) as a marker of yolk sac (YS) endothelium and definitive hematopoietic stem and progenitor cells (HSPCs). Endothelium in mid-gestation YS and vitelline vessels, but not the dorsal aorta and placenta, were labeled by Lyve1-Cre. Most YS HSPCs and erythro-myeloid progenitors were Lyve1-Cre lineage traced, but primitive erythroid cells were not, suggesting that they represent distinct lineages. Fetal liver (FL) and adult HSPCs showed 35%-40% Lyve1-Cre marking. Analysis of circulation-deficient Ncx1-/- concepti identified the YS as a major source of Lyve1-Cre labeled HSPCs. FL proerythroblast marking was extensive at embryonic day (E) 11.5-13.5, but decreased to hematopoietic stem cell (HSC) levels by E16.5, suggesting that HSCs from multiple sources became responsible for erythropoiesis. Lyve1-Cre thus marks the divergence between YS primitive and definitive hematopoiesis and provides a tool for targeting YS definitive hematopoiesis and FL colonization.

Keywords: LYVE1; definitive hematopoiesis; fetal liver; hemogenic endothelium; lineage tracing; primitive hematopoiesis; yolk sac.

Publication types

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

MeSH terms

  • Aging
  • Animals
  • Cell Lineage*
  • Erythroid Cells / cytology*
  • Erythroid Cells / metabolism*
  • Erythropoiesis
  • Female
  • Fetus / cytology
  • Gene Deletion
  • Hemangioblasts / metabolism*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Integrases / metabolism
  • Liver / embryology
  • Mice, Inbred C57BL
  • Pregnancy
  • Time Factors
  • Vesicular Transport Proteins / metabolism*
  • Yolk Sac / metabolism*


  • LYVE1 protein, mouse
  • Vesicular Transport Proteins
  • Cre recombinase
  • Integrases