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

Author

Listed:
  • Weizhen Jia

    (Osaka University, Suita)

  • Lingyu Kong

    (Harbin Medical University Cancer Hospital)

  • Hiroyasu Kidoya

    (Osaka University, Suita)

  • Hisamichi Naito

    (Osaka University, Suita)

  • Fumitaka Muramatsu

    (Osaka University, Suita)

  • Yumiko Hayashi

    (Osaka University, Suita)

  • Han-Yun Hsieh

    (Osaka University, Suita)

  • Daishi Yamakawa

    (Mie University Graduate School of Medicine)

  • Daniel K. Hsu

    (University of California-Davis)

  • Fu-Tong Liu

    (University of California-Davis
    Academia Sinica)

  • Nobuyuki Takakura

    (Osaka University, Suita)

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.

Suggested Citation

  • 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, 2021. "Indispensable role of Galectin-3 in promoting quiescence of hematopoietic stem cells," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22346-2
    DOI: 10.1038/s41467-021-22346-2
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