Hepatoblasts comprise a niche for fetal liver erythropoiesis through cytokine production

Biochem Biophys Res Commun. 2011 Jul 1;410(2):301-6. doi: 10.1016/j.bbrc.2011.05.137. Epub 2011 May 30.


In mammals, definitive erythropoiesis first occurs in fetal liver (FL), although little is known about how the process is regulated. FL consists of hepatoblasts, sinusoid endothelial cells and hematopoietic cells. To determine niche cells for fetal liver erythropoiesis, we isolated each FL component by flow cytometry. mRNA analysis suggested that Dlk-1-expressing hepatoblasts primarily expressed EPO and SCF, genes encoding erythropoietic cytokines. EPO protein was detected predominantly in hepatoblasts, as assessed by ELISA and immunohistochemistry, and was not detected in sinusoid endothelial cells and hematopoietic cells. To characterize hepatoblast function in FL, we analyzed Map2k4(-/-) mouse embryos, which lack hepatoblasts, and observed down-regulation of EPO and SCF expression in FL relative to wild-type mice. Our observations demonstrate that hepatoblasts comprise a niche for erythropoiesis through cytokine secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / biosynthesis*
  • Down-Regulation
  • Erythropoiesis*
  • Fetus / physiology*
  • Flow Cytometry
  • Hematopoietic Stem Cells / physiology*
  • Liver / embryology*
  • MAP Kinase Kinase 4 / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR


  • Cytokines
  • MAP Kinase Kinase 4
  • Map2k4 protein, mouse