Deubiquitinase Mysm1 regulates neural stem cell proliferation and differentiation by controlling Id4 expression.
Cell Death Dis
; 15(2): 129, 2024 02 12.
Article
em En
| MEDLINE
| ID: mdl-38342917
ABSTRACT
Neural stem cells (NSCs) are critical for brain development and maintenance of neurogenesis. However, the molecular mechanisms that regulate NSC proliferation and differentiation remain unclear. Mysm1 is a deubiquitinase and is essential for the self-renewal and differentiation of several stem cells. It is unknown whether Mysm1 plays an important role in NSCs. Here, we found that Mysm1 was expressed in NSCs and its expression was increased with age in mice. Mice with Mysm1 knockdown by crossing Mysm1 floxed mice with Nestin-Cre mice exhibited abnormal brain development with microcephaly. Mysm1 deletion promoted NSC proliferation and apoptosis, resulting in depletion of the stem cell pool. In addition, Mysm1-deficient NSCs skewed toward neurogenesis instead of astrogliogenesis. Mechanistic investigations with RNA sequencing and genome-wide CUT&Tag analysis revealed that Mysm1 epigenetically regulated Id4 transcription by regulating histone modification at the promoter region. After rescuing the expression of Id4, the hyperproliferation and imbalance differentiation of Mysm1-deficient NSCs was reversed. Additionally, knockdown Mysm1 in aged mice could promote NSC proliferation. Collectively, the present study identified a new factor Mysm1 which is essential for NSC homeostasis and Mysm1-Id4 axis may be an ideal target for proper NSC proliferation and differentiation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neurais
/
Proteases Específicas de Ubiquitina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cell Death Dis
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China