Single-molecule imaging of transcription dynamics in somatic stem cells

Justin C. Wheat, Yehonatan Sella, Michael Willcockson, Arthur I. Skoultchi, Aviv Bergman, Robert H. Singer and Ulrich Steidl ()
Additional contact information
Justin C. Wheat: Albert Einstein College of Medicine
Yehonatan Sella: Albert Einstein College of Medicine
Michael Willcockson: Albert Einstein College of Medicine
Arthur I. Skoultchi: Albert Einstein College of Medicine
Aviv Bergman: Albert Einstein College of Medicine
Robert H. Singer: Albert Einstein College of Medicine
Ulrich Steidl: Albert Einstein College of Medicine

Nature, 2020, vol. 583, issue 7816, 431-436

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41586-020-2432-4 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:583:y:2020:i:7816:d:10.1038_s41586-020-2432-4

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-2432-4

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().