Indispensable role of Galectin-3 in promoting quiescence of hematopoietic stem cells
Weizhen Jia, Lingyu Kong, Hiroyasu Kidoya, Hisamichi Naito, Fumitaka Muramatsu, Yumiko Hayashi, Han‐Yun Hsieh, Daishi Yamakawa, Daniel K. Hsu, Fu‐Tong Liu, Nobuyuki Takakura
Abstract
Abstract Hematopoietic stem cells (HSCs) in adult bone marrow (BM) are usually maintained in a state of quiescence. The cellular mechanism coordinating the balance between HSC quiescence and differentiation is not fully understood. Here, we report that galactose-binding lectin-3 (galectin-3; Gal-3) is upregulated by Tie2 or Mpl activation to maintain quiescence. Conditional overexpression of Gal-3 in mouse HSCs under the transcriptional control of Tie2 or Vav1 promoters (Gal-3 Tg) causes cell cycle retardation via induction of p21. Conversely, the cell cycle of long-term repopulating HSCs (LT-HSCs) in Gal-3-deficient (Gal-3 -/- ) mice is accelerated, resulting in their exhaustion. Mechanistically, Gal-3 regulates p21 transcription by forming a complex with Sp1, thus blocking cell cycle entry. These results demonstrate that Gal-3 is a negative regulator of cell-cycling in HSCs and plays a crucial role in adult hematopoiesis to prevent HSC exhaustion.