Negative regulation of the differentiation of flk2 cd34 lsk hematopoietic stem cells by eklf/klf1

Chun Hao Hung, Keh Yang Wang, Yae Huei Liou, Jing Ping Wang, Anna Yu Szu Huang, Tung Liang Lee, Si Tse Jiang, Nah Shih Liao, Yu Chiau Shyu, Che Kun James Shen

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Erythroid Krüppel-like factor (EKLF/KLF1) was identified initially as a critical erythroid-specific transcription factor and was later found to be also expressed in other types of hematopoietic cells, including megakaryocytes and several progenitors. In this study, we have examined the regulatory effects of EKLF on hematopoiesis by comparative analysis of E14.5 fetal livers from wild-type and Eklf gene knockout (KO) mouse embryos. Depletion of EKLF expression greatly changes the populations of different types of hematopoietic cells, including, unexpectedly, the long-term hematopoietic stem cells Flk2 CD34 Lin Sca1+ c-Kit+ (LSK)-HSC. In an interesting correlation, Eklf is expressed at a relatively high level in multipotent progenitor (MPP). Furthermore, EKLF appears to repress the expression of the colony-stimulating factor 2 receptor β subunit (CSF2RB). As a result, Flk2 CD34 LSK-HSC gains increased differentiation capability upon depletion of EKLF, as demonstrated by the methylcellulose colony formation assay and by serial transplantation experiments in vivo. Together, these data demonstrate the regulation of hematopoiesis in vertebrates by EKLF through its negative regulatory effects on the differentiation of the hematopoietic stem and progenitor cells, including Flk2 CD34 LSK-HSCs.

Original languageEnglish
Article number8448
Pages (from-to)1-15
Number of pages15
JournalInternational journal of molecular sciences
Volume21
Issue number22
DOIs
Publication statusPublished - Nov 2 2020

Keywords

  • Differentiation
  • EKLF/KLF1
  • Flk2-CD34-HSC
  • Hematopoiesis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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