UB Paderborn / Katalog / Suche / Details

Autor(en) / Beteiligte

Titel

FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age

Ist Teil von

Ort / Verlag

England

Erscheinungsjahr

2020

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

Tissue regeneration declines with ageing but little is known about whether this arises from changes in stem-cell heterogeneity. Here, in homeostatic skeletal muscle, we identify two quiescent stem-cell states distinguished by relative CD34 expression: CD34 , with stemness properties (genuine state), and CD34 , committed to myogenic differentiation (primed state). The genuine-quiescent state is unexpectedly preserved into later life, succumbing only in extreme old age due to the acquisition of primed-state traits. Niche-derived IGF1-dependent Akt activation debilitates the genuine stem-cell state by imposing primed-state features via FoxO inhibition. Interventions to neutralize Akt and promote FoxO activity drive a primed-to-genuine state conversion, whereas FoxO inactivation deteriorates the genuine state at a young age, causing regenerative failure of muscle, as occurs in geriatric mice. These findings reveal transcriptional determinants of stem-cell heterogeneity that resist ageing more than previously anticipated and are only lost in extreme old age, with implications for the repair of geriatric muscle.

Sprache: Englisch
Identifikatoren: eISSN: 1476-4679
DOI: 10.1038/s41556-020-00593-7
Titel-ID: cdi_pubmed_primary_33106654

Format: –
Schlagworte: Age Factors, Animals, Antigens, CD34 - metabolism, Cardiotoxins - toxicity, Cell Cycle Proteins - genetics, Cell Cycle Proteins - metabolism, Cell Proliferation - drug effects, Cell Proliferation - genetics, Cell Self Renewal - drug effects, Cell Self Renewal - genetics, Cells, Cultured, Cellular Senescence - drug effects, Cellular Senescence - genetics, Forkhead Box Protein O1 - genetics, Forkhead Box Protein O1 - metabolism, Forkhead Box Protein O3 - genetics, Forkhead Box Protein O3 - metabolism, Forkhead Transcription Factors - genetics, Forkhead Transcription Factors - metabolism, Gene Expression Regulation, Male, Mice, Inbred C57BL, Mice, Knockout, Mice, SCID, Muscle, Skeletal - drug effects, Muscle, Skeletal - metabolism, Muscle, Skeletal - pathology, Muscle, Skeletal - transplantation, Phenotype, Proto-Oncogene Proteins c-akt - metabolism, Regeneration - drug effects, Regeneration - genetics, Satellite Cells, Skeletal Muscle - drug effects, Satellite Cells, Skeletal Muscle - metabolism, Satellite Cells, Skeletal Muscle - pathology, Satellite Cells, Skeletal Muscle - transplantation, Signal Transduction, Stem Cell Niche

Empfehlungen zum selben Thema automatisch vorgeschlagen von bX