Article ; Online: Maintenance of mouse hematopoietic stem cells ex vivo by reprogramming cellular metabolism.
2015 Volume 125, Issue 10, Page(s) 1562–1565
Abstract: ... metabolic pathways represents an effective new strategy for ex vivo maintenance of HSCs. ... The difficulty in maintaining the reconstituting capabilities of hematopoietic stem cells (HSCs ... reprogrammed cellular metabolism from mitochondrial aerobic metabolism to glycolysis, resulting in a remarkable ...
| Abstract | The difficulty in maintaining the reconstituting capabilities of hematopoietic stem cells (HSCs) in culture outside of the bone marrow microenvironment has severely limited their utilization for clinical therapy. This hurdle is largely due to the differentiation of long-term stem cells. Emerging evidence suggests that energy metabolism plays an important role in coordinating HSC self-renewal and differentiation. Here, we show that treatment with alexidine dihydrochloride, an antibiotic and a selective inhibitor of the mitochondrial phosphatase Ptpmt1, which is crucial for the differentiation of HSCs, reprogrammed cellular metabolism from mitochondrial aerobic metabolism to glycolysis, resulting in a remarkable preservation of long-term HSCs ex vivo in part through hyperactivation of adenosine 5'-monophosphate-activated protein kinase (AMPK). In addition, inhibition of mitochondrial metabolism and activation of AMPK by metformin, a diabetes drug, also decreased differentiation and helped maintain stem cells in culture. Thus, manipulating metabolic pathways represents an effective new strategy for ex vivo maintenance of HSCs. |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| MeSH term(s) | AMP-Activated Protein Kinases/metabolism ; Aerobiosis/drug effects ; Animals ; Biguanides/pharmacology ; Cell Differentiation/drug effects ; Cells, Cultured ; Cellular Reprogramming/drug effects ; Enzyme Activation/drug effects ; Enzyme Inhibitors/pharmacology ; Glycolysis/drug effects ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/drug effects ; Hematopoietic Stem Cells/metabolism ; Hypoglycemic Agents/pharmacology ; Metformin/pharmacology ; Mice ; Oxygen Consumption/drug effects ; PTEN Phosphohydrolase/antagonists & inhibitors | ||||||||||
| Chemical Substances | Biguanides ; Enzyme Inhibitors ; Hypoglycemic Agents ; Metformin (9100L32L2N) ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; Ptpmt1 protein, mouse (EC 3.1.3.27) ; PTEN Phosphohydrolase (EC 3.1.3.67) ; alexidine (GVN71CAL3G) | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2015-01-15 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural | ||||||||||
| ZDB-ID | 80069-7 | ||||||||||
| ISSN | 1528-0020 ; 0006-4971 | ||||||||||
| ISSN (online) | 1528-0020 | ||||||||||
| ISSN | 0006-4971 | ||||||||||
| DOI | 10.1182/blood-2014-04-568949 | ||||||||||
| Shelf mark |
|
||||||||||
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Uh III Zs.140: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
|||
| Zs.MO 364: Show issues |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.