The Chromatin Remodeling Complex CHD1 Regulates the Primitive State of Mesenchymal Stromal Cells to Control Their Stem Cell Supporting Activity.
Stem Cells Dev
; 30(7): 363-373, 2021 04 01.
Article
em En
| MEDLINE
| ID: mdl-33593142
ABSTRACT
The primitive state (stemness) of mesenchymal stromal cells (MSCs) is responsible for supporting the function of tissue-specific stem cells to regenerate damaged tissues. However, molecular mechanisms regulating the stemness of MSCs remain unknown. In this study, we found that the primitive state of MSCs is hierarchically regulated by the expression levels of the chromatin remodeling complex, CHD1, with CHD1 expression levels higher in the undifferentiated state, and decreasing upon MSC differentiation. Consistently, CHD1 expression levels decrease during progressive loss of clonogenic progenitors (CFU-F) induced by passage cultures. Moreover, knockdown (KD) of CHD1 decreased CFU-F frequency, whereas CHD1 overexpression increased it. In addition, the expression of stem cell-specific genes was down- or upregulated upon KD or overexpression of CHD1, respectively, accompanied by associated changes in chromatin condensation. Importantly, altering CHD1 expression levels affected the ability of MSCs to support the self-renewing expansion of hematopoietic stem cells (HSCs). Furthermore, CHD1 levels were significantly decreased in MSCs from acute myeloid leukemia or aplastic anemia patients, where CFU-F and HSC-supporting activities are lost. Altogether, these findings show that chromatin remodeling by CHD1 is a molecular parameter that influences the primitive state of MSCs and their stem cell-supporting activity, which controls tissue regeneration.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Diferenciação Celular
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Regulação da Expressão Gênica
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DNA Helicases
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Montagem e Desmontagem da Cromatina
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Proteínas de Ligação a DNA
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Células-Tronco Mesenquimais
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Stem Cells Dev
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article