Indispensable role of Galectin-3 in promoting quiescence of hematopoietic stem cells

• Jia Weizhen

• Kong Lingyu

• Kidoya Hiroyasu

• Naito Hisamichi

• Muramatsu Fumitaka

• Hayashida Yumiko

• Hsieh Han-Yun

• Yamakawa Daishi

• Hsu Daniel K.

• Liu Fu-Tong

• Takakura Nobuyuki

• 内藤 尚道

• 高倉 伸幸

抄録

金沢大学医薬保健研究域医学系

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. © 2021, The Author(s).

収録刊行物

• Nature Communications

  Nature Communications 12 (1), 2118-, 2021-04-09

  Nature Research / Nature Publishing Group

詳細情報

• CRID: 1390572175477162112
• NII論文ID: 120007096897
• NII書誌ID: AA12645905
• ISSN: 20411723
• DOI: 10.24517/00062984
• Web Site: http://hdl.handle.net/2297/00062984
• 本文言語コード: en
• データソース種別:
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  • IRDB
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