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

Nat Commun. 2021 Apr 9;12(1):2118. doi: 10.1038/s41467-021-22346-2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / physiology*
  • Animals
  • Cell Cycle / physiology*
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Female
  • Galectin 3 / genetics
  • Galectin 3 / metabolism*
  • Hematopoiesis / genetics*
  • Hematopoietic Stem Cells / physiology*
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Receptor, TIE-2 / metabolism
  • Receptors, Thrombopoietin / metabolism
  • Sp1 Transcription Factor / metabolism
  • Transcriptional Activation
  • Up-Regulation


  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Galectin 3
  • Lgals3 protein, mouse
  • Mpl protein, mouse
  • Receptors, Thrombopoietin
  • Sp1 Transcription Factor
  • Receptor, TIE-2
  • Tek protein, mouse