Rate of Progression through a Continuum of Transit-Amplifying Progenitor Cell States Regulates Blood Cell Production.
Dev Cell
; 49(1): 118-129.e7, 2019 04 08.
Article
em En
| MEDLINE
| ID: mdl-30827895
ABSTRACT
The nature of cell-state transitions during the transit-amplifying phases of many developmental processes-hematopoiesis in particular-is unclear. Here, we use single-cell RNA sequencing to demonstrate a continuum of transcriptomic states in committed transit-amplifying erythropoietic progenitors, which correlates with a continuum of proliferative potentials in these cells. We show that glucocorticoids enhance erythrocyte production by slowing the rate of progression through this developmental continuum of transit-amplifying progenitors, permitting more cell divisions prior to terminal erythroid differentiation. Mechanistically, glucocorticoids prolong expression of genes that antagonize and slow induction of genes that drive terminal erythroid differentiation. Erythroid progenitor daughter cell pairs have similar transcriptomes with or without glucocorticoid stimulation, indicating largely symmetric cell division. Thus, the rate of progression along a developmental continuum dictates the absolute number of erythroid cells generated from each transit-amplifying progenitor, suggesting a paradigm for regulating the total output of differentiated cells in numerous other developmental processes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Sanguíneas
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Células Precursoras Eritroides
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Proliferação de Células
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Hematopoese
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article