Single-molecule imaging of transcription dynamics in somatic stem cells.

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.

journal_name

Nature

journal_title

Nature

authors

Wheat JC,Sella Y,Willcockson M,Skoultchi AI,Bergman A,Singer RH,Steidl U

doi

10.1038/s41586-020-2432-4

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

431-436

issue

7816

eissn

0028-0836

issn

1476-4687

pii

10.1038/s41586-020-2432-4

journal_volume

583

pub_type

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