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Clonally heritable gene expression imparts a layer of diversity within cell types
Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
Mathematics Department, University of California, Santa Cruz, CA, USA.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.ORCID iD: 0000-0002-9795-8033
Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
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2024 (English)In: Cell systems, E-ISSN 2405-4720, Vol. 15, no 2, p. 149-Article in journal (Refereed) Published
Abstract [en]

Cell types can be classified according to shared patterns of transcription. Non-genetic variability among individual cells of the same type has been ascribed to stochastic transcriptional bursting and transient cell states. Using high-coverage single-cell RNA profiling, we asked whether long-term, heritable differences in gene expression can impart diversity within cells of the same type. Studying clonal human lymphocytes and mouse brain cells, we uncovered a vast diversity of heritable gene expression patterns among different clones of cells of the same type in vivo. We combined chromatin accessibility and RNA profiling on different lymphocyte clones to reveal thousands of regulatory regions exhibiting interclonal variation, which could be directly linked to interclonal variation in gene expression. Our findings identify a source of cellular diversity, which may have important implications for how cellular populations are shaped by selective processes in development, aging, and disease. A record of this paper's transparent peer review process is included in the supplemental information.

Place, publisher, year, edition, pages
Elsevier BV , 2024. Vol. 15, no 2, p. 149-
Keywords [en]
clonality, epigenetics, gene expression regulation, heritability, immunology, lineage tracing, memory, neuroscience, RNA-seq, single cell
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:kth:diva-344172DOI: 10.1016/j.cels.2024.01.004PubMedID: 38340731Scopus ID: 2-s2.0-85185847086OAI: oai:DiVA.org:kth-344172DiVA, id: diva2:1842892
Note

QC 20240308

Available from: 2024-03-06 Created: 2024-03-06 Last updated: 2024-03-08Bibliographically approved

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Ratz, MichaelToosi, HoseinBergenstråhle, JosephLagergren, JensLundeberg, Joakim

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Ratz, MichaelToosi, HoseinBergenstråhle, JosephLagergren, JensLundeberg, Joakim
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