Cell states beyond transcriptomics: Integrating structural organization and gene expression in hiPSC-derived cardiomyocytes.

Autor: Gerbin KA; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Grancharova T; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Donovan-Maiye RM; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Hendershott MC; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Anderson HG; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Brown JM; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Chen J; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Dinh SQ; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Gehring JL; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Johnson GR; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Lee H; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Nath A; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Nelson AM; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Sluzewski MF; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Viana MP; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Yan C; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Zaunbrecher RJ; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Cordes Metzler KR; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Gaudreault N; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Knijnenburg TA; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Rafelski SM; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA., Theriot JA; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA; Department of Biology and Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA., Gunawardane RN; Allen Institute for Cell Science, 615 Westlake Ave N, Seattle, WA, USA. Electronic address: rug@alleninstitute.org.
Jazyk: angličtina
Zdroj: Cell systems [Cell Syst] 2021 Jun 16; Vol. 12 (6), pp. 670-687.e10. Date of Electronic Publication: 2021 May 26.
DOI: 10.1016/j.cels.2021.05.001
Abstrakt: Although some cell types may be defined anatomically or by physiological function, a rigorous definition of cell state remains elusive. Here, we develop a quantitative, imaging-based platform for the systematic and automated classification of subcellular organization in single cells. We use this platform to quantify subcellular organization and gene expression in >30,000 individual human induced pluripotent stem cell-derived cardiomyocytes, producing a publicly available dataset that describes the population distributions of local and global sarcomere organization, mRNA abundance, and correlations between these traits. While the mRNA abundance of some phenotypically important genes correlates with subcellular organization (e.g., the beta-myosin heavy chain, MYH7), these two cellular metrics are heterogeneous and often uncorrelated, which suggests that gene expression alone is not sufficient to classify cell states. Instead, we posit that cell state should be defined by observing full distributions of quantitative, multidimensional traits in single cells that also account for space, time, and function.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE