RRC ID 64304
Author Jia W, Kong L, Kidoya H, Naito H, Muramatsu F, Hayashi Y, Hsieh HY, Yamakawa D, Hsu DK, Liu FT, Takakura N.
Title Indispensable role of Galectin-3 in promoting quiescence of hematopoietic stem cells.
Journal Nat Commun
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.
Volume 12(1)
Pages 2118
Published 2021-4-9
DOI 10.1038/s41467-021-22346-2
PII 10.1038/s41467-021-22346-2
PMID 33837181
PMC PMC8035175
MeSH 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
IF 12.121
Human and Animal Cells Ba/F3(RCB0805) OP9(RCB1124)