Single-molecule imaging of transcription dynamics in somatic stem cells.
Nature
; 583(7816): 431-436, 2020 07.
Article
en En
| MEDLINE
| ID: mdl-32581360
ABSTRACT
Molecular noise is a natural phenomenon that is inherent to all biological systems1,2. How stochastic processes give rise to the robust outcomes that support tissue homeostasis remains unclear. Here we use single-molecule RNA fluorescent in situ hybridization (smFISH) on mouse stem cells derived from haematopoietic tissue to measure the transcription dynamics of three key genes that encode transcription factors PU.1 (also known as Spi1), Gata1 and Gata2. We find that infrequent, stochastic bursts of transcription result in the co-expression of these antagonistic transcription factors in the majority of haematopoietic stem and progenitor cells. Moreover, by pairing smFISH with time-lapse microscopy and the analysis of pedigrees, we find that although individual stem-cell clones produce descendants that are in transcriptionally related states-akin to a transcriptional priming phenomenon-the underlying transition dynamics between states are best captured by stochastic and reversible models. As such, a stochastic process can produce cellular behaviours that may be incorrectly inferred to have arisen from deterministic dynamics. We propose a model whereby the intrinsic stochasticity of gene expression facilitates, rather than impedes, the concomitant maintenance of transcriptional plasticity and stem cell robustness.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transcripción Genética
/
Regulación de la Expresión Génica
/
Células Madre Adultas
/
Imagen Individual de Molécula
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Nature
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos