Zfat Is Indispensable for the Development of Erythroid Cells in the Fetal Liver

Anticancer Res. 2019 Aug;39(8):4495-4502. doi: 10.21873/anticanres.13625.

Abstract

Background/aim: In mice, fetal liver is the first tissue of definitive erythropoiesis for definitive erythroid expansion and maturation. ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in primitive hematopoiesis and T cell development. The aim of this study was to examine whether or not Zfat is involved in definitive erythropoiesis in the fetal liver during mammalian development.

Materials and methods: The role of Zfat during mouse fetal erythropoiesis in the fetal liver was examined using tamoxifen-inducible CreERT2 Zfat-deficient mice.

Results: Zfat-deficient mice exhibit moderate anemia with small and pale fetal liver through a decreased number of erythroblasts by E12.5. Apoptosis sensitivity in fetal liver erythroid progenitors was enhanced by Zfat-deficiency ex vivo. Moreover, Zfat knockdown partially inhibited CD71-/lowTer119- to CD71highTer119- transition of fetal liver erythroid progenitors with impairment in the elevation of CD71 expression.

Conclusion: Zfat plays a critical role for erythropoiesis in the fetal liver.

Keywords: Zfat; definitive erythropoiesis; fetal liver; transcription factor.

MeSH terms

  • Animals
  • Antigens, CD / genetics*
  • Apoptosis / genetics
  • Cell Differentiation / genetics
  • Erythroid Cells / metabolism
  • Erythroid Cells / pathology
  • Erythropoiesis / genetics*
  • Fetal Development / genetics
  • Fetus
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Humans
  • Liver / growth & development*
  • Liver / metabolism
  • Mice
  • Receptors, Transferrin / genetics*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism
  • Thyroiditis, Autoimmune / genetics
  • Thyroiditis, Autoimmune / pathology
  • Transcription Factors / genetics*

Substances

  • Antigens, CD
  • CD71 antigen
  • Receptors, Transferrin
  • Transcription Factors
  • ZFAT protein, mouse