Epigenetic reversal of hematopoietic stem cell aging in Phf6-knockout mice.
Nat Aging
; 2(11): 1008-1023, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-37118089
ABSTRACT
Aging is characterized by an accumulation of myeloid-biased hematopoietic stem cells (HSCs) with reduced developmental potential. Genotoxic stress and epigenetic alterations have been proposed to mediate age-related HSC loss of regenerative and self-renewal potential. However, the mechanisms underlying these changes remain largely unknown. Genetic inactivation of the plant homeodomain 6 (Phf6) gene, a nucleolar and chromatin-associated factor, antagonizes age-associated HSC decline. Immunophenotyping, single-cell transcriptomic analyses and transplantation assays demonstrated markedly decreased accumulation of immunophenotypically defined HSCs, reduced myeloid bias and increased hematopoietic reconstitution capacity with preservation of lymphoid differentiation potential in Phf6-knockout HSCs from old mice. Moreover, deletion of Phf6 in aged mice rejuvenated immunophenotypic, transcriptional and functional hallmarks of aged HSCs. Long-term HSCs from old Phf6-knockout mice showed epigenetic rewiring and transcriptional programs consistent with decreased genotoxic stress-induced HSC aging. These results identify Phf6 as an important epigenetic regulator of HSC aging.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
/
Células-Tronco Hematopoéticas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article