FOXG1 dose tunes cell proliferation dynamics in human forebrain progenitor cells.
Stem Cell Reports
; 17(3): 475-488, 2022 03 08.
Article
em En
| MEDLINE
| ID: mdl-35148845
ABSTRACT
Heterozygous loss-of-function mutations in Forkhead box G1 (FOXG1), a uniquely brain-expressed gene, cause microcephaly, seizures, and severe intellectual disability, whereas increased FOXG1 expression is frequently observed in glioblastoma. To investigate the role of FOXG1 in forebrain cell proliferation, we modeled FOXG1 syndrome using cells from three clinically diagnosed cases with two sex-matched healthy parents and one unrelated sex-matched control. Cells with heterozygous FOXG1 loss showed significant reduction in cell proliferation, increased ratio of cells in G0/G1 stage of the cell cycle, and increased frequency of primary cilia. Engineered loss of FOXG1 recapitulated this effect, while isogenic repair of a patient mutation reverted output markers to wild type. An engineered inducible FOXG1 cell line derived from a FOXG1 syndrome case demonstrated that FOXG1 dose-dependently affects all cell proliferation outputs measured. These findings provide strong support for the critical importance of FOXG1 levels in controlling human brain cell growth in health and disease.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição Forkhead
/
Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Stem Cell Reports
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Canadá