Homeodomain transcription factor Meis1 is a critical regulator of adult bone marrow hematopoiesis

Reina Ariki, Satoru Morikawa, Yo Mabuchi, Sadafumi Suzuki, Mayuka Nakatake, Kentaro Yoshioka, Shinya Hidano, Hiromitsu Nakauchi, Yumi Matsuzaki, Takuro Nakamura, Ryo Goitsuka

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25 Citations (Scopus)

Abstract

Hematopoietic stem cells in the bone marrow have the capacity to both self-renew and to generate all cells of the hematopoietic system. The balance of these two activities is controlled by hematopoietic stem cell-intrinsic regulatory mechanisms as well as extrinsic signals from the microenvironment. Here we demonstrate that Meis1, a TALE family homeodomain transcription factor involved in numerous embryonic developmental processes, is selectively expressed in hematopoietic stem/progenitor cells. Conditional Meis1 knockout in adult hematopoietic cells resulted in a significant reduction in the hematopoietic stem/progenitor cells. Suppression of hematopoiesis by Meis1 deletion appears to be caused by impaired self-renewal activity and reduced cellular quiescence of hematopoietic stem/progenitor cells in a cell autonomous manner, resulting in stem cell exhaustion and defective long-term hematopoiesis. Meis1 deficiency down-regulated a subset of Pbx1-dependent hematopoietic stem cell signature genes, suggesting a functional link between them in the maintenance of hematopoietic stem/progenitor cells. These results show the importance of Meis1 in adult hematopoiesis.

Original languageEnglish
Article numbere87646
JournalPloS one
Volume9
Issue number2
DOIs
Publication statusPublished - 2014 Feb 3

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Ariki, R., Morikawa, S., Mabuchi, Y., Suzuki, S., Nakatake, M., Yoshioka, K., Hidano, S., Nakauchi, H., Matsuzaki, Y., Nakamura, T., & Goitsuka, R. (2014). Homeodomain transcription factor Meis1 is a critical regulator of adult bone marrow hematopoiesis. PloS one, 9(2), [e87646]. https://doi.org/10.1371/journal.pone.0087646