Metabolic adaptation pilots the differentiation of human hematopoietic cells.
Life Sci Alliance
; 7(8)2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38802246
ABSTRACT
A continuous supply of energy is an essential prerequisite for survival and represents the highest priority for the cell. We hypothesize that cell differentiation is a process of optimization of energy flow in a changing environment through phenotypic adaptation. The mechanistic basis of this hypothesis is provided by the established link between core energy metabolism and epigenetic covalent modifications of chromatin. This theory predicts that early metabolic perturbations impact subsequent differentiation. To test this, we induced transient metabolic perturbations in undifferentiated human hematopoietic cells using pharmacological inhibitors targeting key metabolic reactions. We recorded changes in chromatin structure and gene expression, as well as phenotypic alterations by single-cell ATAC and RNA sequencing, time-lapse microscopy, and flow cytometry. Our observations suggest that these metabolic perturbations are shortly followed by alterations in chromatin structure, leading to changes in gene expression. We also show that these transient fluctuations alter the differentiation potential of the cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Cromatina
/
Diferenciação Celular
/
Metabolismo Energético
Limite:
Humans
Idioma:
En
Revista:
Life Sci Alliance
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
França