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- Title
Indispensable role of Galectin-3 in promoting quiescence of hematopoietic stem cells.
- Authors
Jia, Weizhen; Kong, Lingyu; Kidoya, Hiroyasu; Naito, Hisamichi; Muramatsu, Fumitaka; Hayashi, Yumiko; Hsieh, Han-Yun; Yamakawa, Daishi; Hsu, Daniel K.; Liu, Fu-Tong; Takakura, Nobuyuki
- 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. Long term haematopoitic stem cells (LT-HSCs) are in a quiescent state during homeostasis, which is critical for their maintenance. Here, the authors show that Gal-3 expression in LT-HSCs is induced in response to Tie2 and Mpl and is both necessary and sufficient for LT-HSC quiescence through regulation of p21.
- Subjects
HEMATOPOIETIC stem cells; GALECTINS; HEMATOPOIESIS; CELL cycle; STEM cells; BONE marrow
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-22346-2