Reference - Detail
| 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 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 8 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | Ba/F3(RCB0805) OP9(RCB1124) |