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
|
Resource |
Human and Animal Cells |
Ba/F3(RCB0805)
OP9(RCB1124) |