Effects of THAP11 on erythroid differentiation and megakaryocytic differentiation of K562 cells

PLoS One. 2014 Mar 17;9(3):e91557. doi: 10.1371/journal.pone.0091557. eCollection 2014.

Abstract

Hematopoiesis is a complex process regulated by sets of transcription factors in a stage-specific and context-dependent manner. THAP11 is a transcription factor involved in cell growth, ES cell pluripotency, and embryogenesis. Here we showed that THAP11 was down-regulated during erythroid differentiation but up-regulated during megakaryocytic differentiation of cord blood CD34+ cells. Overexpression of THAP11 in K562 cells inhibited the erythroid differentiation induced by hemin with decreased numbers of benzidine-positive cells and decreased mRNA levels of α-globin (HBA) and glycophorin A (GPA), and knockdown of THAP11 enhanced the erythroid differentiation. Conversely, THAP11 overexpression accelerated the megakaryocytic differentiation induced by phorbol myristate acetate (PMA) with increased percentage of CD41+ cells, increased numbers of 4N cells, and elevated CD61 mRNA levels, and THAP11 knockdown attenuated the megakaryocytic differentiation. The expression levels of transcription factors such as c-Myc, c-Myb, GATA-2, and Fli1 were changed by THAP11 overexpression. In this way, our results suggested that THAP11 reversibly regulated erythroid and megakaryocytic differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD34 / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics*
  • Erythroid Cells / cytology*
  • Erythroid Cells / metabolism*
  • Fetal Blood / cytology
  • Gene Expression Regulation
  • Hematopoiesis / genetics*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Hemin / pharmacology
  • Humans
  • K562 Cells
  • Megakaryocytes / cytology*
  • Megakaryocytes / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Transcription Factors / metabolism

Substances

  • Antigens, CD34
  • RNA, Messenger
  • Repressor Proteins
  • THAP11 protein, human
  • Transcription Factors
  • Hemin

Grants and funding

This study is partly supported by Chinese National Natural Science Foundation Projects (81222005, 81070435); and Major State Basic Research of China (2012AA020206, 2013CB910800). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.