In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells.

Autor:	Kubasova N; Chronic Diseases Research Centre, Nova Medical School, CEDOC, Lisbon, Portugal.; Genetagus, Egas Moniz - Cooperativa de Ensino Superior, CRL, Monte de Caparica, Portugal., Alves-Pereira CF; Center of Cancer Systems Biology, Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States.; Department of Genetics, Harvard Medical School, Boston, MA, United States.; Broad Institute of MIT and Harvard, Cambridge, MA, United States.; Department of Genetics, Smurfit Institute of Genetics, Trinity College Dublin, University of Dublin, Dublin, Ireland., Gupta S; Center of Cancer Systems Biology, Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States.; Department of Genetics, Harvard Medical School, Boston, MA, United States.; Broad Institute of MIT and Harvard, Cambridge, MA, United States., Vinogradova S; Center of Cancer Systems Biology, Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States.; Department of Genetics, Harvard Medical School, Boston, MA, United States.; Broad Institute of MIT and Harvard, Cambridge, MA, United States., Gimelbrant A; Center of Cancer Systems Biology, Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States.; Department of Genetics, Harvard Medical School, Boston, MA, United States.; Broad Institute of MIT and Harvard, Cambridge, MA, United States., Barreto VM; Chronic Diseases Research Centre, Nova Medical School, CEDOC, Lisbon, Portugal.; UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Costa da Caparica, Portugal.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2022 Aug 08; Vol. 10, pp. 827774. Date of Electronic Publication: 2022 Aug 08 (Print Publication: 2022).
DOI:	10.3389/fcell.2022.827774
Abstrakt:	Evaluating the epigenetic landscape in the stem cell compartment at the single-cell level is essential to assess the cells' heterogeneity and predict their fate. Here, using a genome-wide transcriptomics approach in vivo , we evaluated the allelic expression imbalance in the progeny of single hematopoietic cells (HSCs) as a read-out of epigenetic marking. After 4 months of extensive proliferation and differentiation, we found that X-chromosome inactivation (XCI) is tightly maintained in all single-HSC derived hematopoietic cells. In contrast, the vast majority of the autosomal genes did not show clonal patterns of random monoallelic expression (RME). However, a persistent allele-specific autosomal transcription in HSCs and their progeny was found in a rare number of cases, none of which has been previously reported. These data show that: 1) XCI and RME in the autosomal chromosomes are driven by different mechanisms; 2) the previously reported high frequency of genes under RME in clones expanded in vitro (up to 15%) is not found in clones undergoing multiple differentiation steps in vivo ; 3) prior to differentiation, HSCs have stable patterns of autosomal RME. We propose that most RME patterns in autosomal chromosomes are erased and established de novo during cell lineage differentiation. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Kubasova, Alves-Pereira, Gupta, Vinogradova, Gimelbrant and Barreto.)
Databáze:	MEDLINE
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