• Reina Ariki, Satoru Morikawa, Yo Mabuchi, Sadafumi Suzuki, Mayuka Nakatake, Kentaro Yoshioka, Shinya Hidano, Hiromitsu Nakauchi, Yumi Matsuzaki, Takuro Nakamura, and Ryo Goitsuka.
• Division of Development and Aging, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
• Plos One. 2014 Jan 1; 9 (2): e87646.

AbstractHematopoietic 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.

31 keywords...

hide…