Integrative single-cell omics analyses reveal epigenetic heterogeneity in mouse embryonic stem cells.
Embryonic 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 i...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-03-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC5862410?pdf=render |
| _version_ | 1818422825999925248 |
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| author | Yanting Luo Jianlin He Xiguang Xu Ming-An Sun Xiaowei Wu Xuemei Lu Hehuang Xie |
| author_facet | Yanting Luo Jianlin He Xiguang Xu Ming-An Sun Xiaowei Wu Xuemei Lu Hehuang Xie |
| author_sort | Yanting Luo |
| collection | DOAJ |
| description | Embryonic 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. |
| first_indexed | 2024-12-14T13:32:25Z |
| format | Article |
| id | doaj.art-742e328decb843cbb1fb60a92fc9806e |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-14T13:32:25Z |
| publishDate | 2018-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-742e328decb843cbb1fb60a92fc9806e2022-12-21T22:59:40ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582018-03-01143e100603410.1371/journal.pcbi.1006034Integrative single-cell omics analyses reveal epigenetic heterogeneity in mouse embryonic stem cells.Yanting LuoJianlin HeXiguang XuMing-An SunXiaowei WuXuemei LuHehuang XieEmbryonic 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.http://europepmc.org/articles/PMC5862410?pdf=render |
| spellingShingle | Yanting Luo Jianlin He Xiguang Xu Ming-An Sun Xiaowei Wu Xuemei Lu Hehuang Xie Integrative single-cell omics analyses reveal epigenetic heterogeneity in mouse embryonic stem cells. PLoS Computational Biology |
| title | Integrative single-cell omics analyses reveal epigenetic heterogeneity in mouse embryonic stem cells. |
| title_full | Integrative single-cell omics analyses reveal epigenetic heterogeneity in mouse embryonic stem cells. |
| title_fullStr | Integrative single-cell omics analyses reveal epigenetic heterogeneity in mouse embryonic stem cells. |
| title_full_unstemmed | Integrative single-cell omics analyses reveal epigenetic heterogeneity in mouse embryonic stem cells. |
| title_short | Integrative single-cell omics analyses reveal epigenetic heterogeneity in mouse embryonic stem cells. |
| title_sort | integrative single cell omics analyses reveal epigenetic heterogeneity in mouse embryonic stem cells |
| url | http://europepmc.org/articles/PMC5862410?pdf=render |
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