Integrative single-cell omics analyses reveal epigenetic heterogeneity in mouse embryonic stem cells

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dc.contributor.authorLuo, Yantingen
dc.contributor.authorHe, Jianlinen
dc.contributor.authorXu, Xiguangen
dc.contributor.authorSun, Ming-anen
dc.contributor.authorWu, Xiaoweien
dc.contributor.authorLu, Xuemeien
dc.contributor.authorXie, Hehuang Daviden
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentStatisticsen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.date.accessioned2018-11-19T18:38:15Zen
dc.date.available2018-11-19T18:38:15Zen
dc.date.issued2018-03en
dc.description.abstractEmbryonic stem cells (ESCs) consist of a population of self-renewing cells displaying extensive phenotypic and functional heterogeneity. Research towards the understanding of the epigenetic mechanisms underlying the heterogeneity among ESCs is still in its initial stage. Key issues, such as how to identify cell-subset specifically methylated loci and how to interpret the biological meanings of methylation variations remain largely unexplored. To fill in the research gap, we implemented a computational pipeline to analyze single-cell methylome and to perform an integrative analysis with single-cell transcriptome data. According to the origins of variation in DNA methylation, we determined the genomic loci associated with allelic-specific methylation or asymmetric DNA methylation, and explored a beta mixture model to infer the genomic loci exhibiting cell-subset specific methylation (CSM). We observed that the putative CSM loci in ESCs are significantly enriched in CpG island (CGI) shelves and regions with histone marks for promoter and enhancer, and the genes hosting putative CSM loci show wide-ranging expression among ESCs. More interestingly, the putative CSM loci may be clustered into co-methylated modules enriching the binding motifs of distinct sets of transcription factors. Taken together, our study provided a novel tool to explore single-cell methylome and transcriptome to reveal the underlying transcriptional regulatory networks associated with epigenetic heterogeneity of ESCs.en
dc.description.sponsorshipThis work was supported by National Institute of Neurological Disorders and Stroke (https://www.ninds.nih.gov/) grant NS094574 to HX, National Natural Science Foundation of China (www.nsfc.gov.cn) grant 91531305 and 31771416 to XL, Strategic Priority Research Program of the Chinese Academy of Sciences (http://english.cas.cn) grant XDB13000000 to XL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pcbi.1006034en
dc.identifier.eissn1553-7358en
dc.identifier.issn1553-734Xen
dc.identifier.issue3en
dc.identifier.othere1006034en
dc.identifier.pmid29561833en
dc.identifier.urihttp://hdl.handle.net/10919/85907en
dc.identifier.volume14en
dc.language.isoen_USen
dc.publisherPLOSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectlarge gene listsen
dc.subjectdna methylationen
dc.subjecttranscription factorsen
dc.subjectself-renewalen
dc.subjecthuman genomeen
dc.subjectdifferentiationen
dc.subjectdynamicsen
dc.subjectexpressionen
dc.subjectmethylomeen
dc.subjectidentificationen
dc.titleIntegrative single-cell omics analyses reveal epigenetic heterogeneity in mouse embryonic stem cellsen
dc.title.serialPLOS Computational Biologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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