Integrative analysis of single-cell RNA-seq and ATAC-seq reveals heterogeneity of induced pluripotent stem cell-derived hepatic organoids
Summary: To gain deeper insights into transcriptomes and epigenomes of organoids, liver organoids from two states (expandable and more differentiated) were subjected to single-cell RNA-seq (scRNA-seq) and single-cell ATAC-seq (scATAC-seq) analyses. Mitochondrial gene expression was higher in differe...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223017522 |
| _version_ | 1797732844463718400 |
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| author | Jong-Hwan Kim Seon Ju Mun Jeong-Hwan Kim Myung Jin Son Seon-Young Kim |
| author_facet | Jong-Hwan Kim Seon Ju Mun Jeong-Hwan Kim Myung Jin Son Seon-Young Kim |
| author_sort | Jong-Hwan Kim |
| collection | DOAJ |
| description | Summary: To gain deeper insights into transcriptomes and epigenomes of organoids, liver organoids from two states (expandable and more differentiated) were subjected to single-cell RNA-seq (scRNA-seq) and single-cell ATAC-seq (scATAC-seq) analyses. Mitochondrial gene expression was higher in differentiated than in non-differentiated hepatocytes, with ATAC-seq peaks increasing near the mitochondrial control region. Differentiation of liver organoids resulted in the expression of transcription factors that act as enhancers and repressors. In addition, epigenetic mechanisms regulating the expression of alpha-fetoprotein (AFP) and albumin (ALB) differed in liver organoids and adult liver. Knockdown of PDX1, an essential transcription factor for pancreas development, led to the hepatic maturation of liver organoids through regulation of AFP and ALB expression. This integrative analysis of the transcriptomes and epigenomes of liver organoids at the single-cell level may contribute to a better understanding of the regulatory networks during liver development and the further development of mature in vitro human liver models. |
| first_indexed | 2024-03-12T12:19:27Z |
| format | Article |
| id | doaj.art-2fd0660c7a624aacaca84486a2a77750 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T12:19:27Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-2fd0660c7a624aacaca84486a2a777502023-08-30T05:54:37ZengElsevieriScience2589-00422023-09-01269107675Integrative analysis of single-cell RNA-seq and ATAC-seq reveals heterogeneity of induced pluripotent stem cell-derived hepatic organoidsJong-Hwan Kim0Seon Ju Mun1Jeong-Hwan Kim2Myung Jin Son3Seon-Young Kim4Korean Bioinformation Center, Daejeon, KoreaStem Cell Convergence Research Center, Daejeon, Korea; Department of Functional Genomics, University of Science and Technology (UST), Daejeon, KoreaPersonalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, KoreaStem Cell Convergence Research Center, Daejeon, Korea; Department of Functional Genomics, University of Science and Technology (UST), Daejeon, Korea; School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea; Corresponding authorKorean Bioinformation Center, Daejeon, Korea; Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea; Department of Functional Genomics, University of Science and Technology (UST), Daejeon, Korea; Corresponding authorSummary: To gain deeper insights into transcriptomes and epigenomes of organoids, liver organoids from two states (expandable and more differentiated) were subjected to single-cell RNA-seq (scRNA-seq) and single-cell ATAC-seq (scATAC-seq) analyses. Mitochondrial gene expression was higher in differentiated than in non-differentiated hepatocytes, with ATAC-seq peaks increasing near the mitochondrial control region. Differentiation of liver organoids resulted in the expression of transcription factors that act as enhancers and repressors. In addition, epigenetic mechanisms regulating the expression of alpha-fetoprotein (AFP) and albumin (ALB) differed in liver organoids and adult liver. Knockdown of PDX1, an essential transcription factor for pancreas development, led to the hepatic maturation of liver organoids through regulation of AFP and ALB expression. This integrative analysis of the transcriptomes and epigenomes of liver organoids at the single-cell level may contribute to a better understanding of the regulatory networks during liver development and the further development of mature in vitro human liver models.http://www.sciencedirect.com/science/article/pii/S2589004223017522Molecular mechanism of gene regulationIntegrative aspects of cell biologyExperimental models in systems biologyTranscriptomics |
| spellingShingle | Jong-Hwan Kim Seon Ju Mun Jeong-Hwan Kim Myung Jin Son Seon-Young Kim Integrative analysis of single-cell RNA-seq and ATAC-seq reveals heterogeneity of induced pluripotent stem cell-derived hepatic organoids iScience Molecular mechanism of gene regulation Integrative aspects of cell biology Experimental models in systems biology Transcriptomics |
| title | Integrative analysis of single-cell RNA-seq and ATAC-seq reveals heterogeneity of induced pluripotent stem cell-derived hepatic organoids |
| title_full | Integrative analysis of single-cell RNA-seq and ATAC-seq reveals heterogeneity of induced pluripotent stem cell-derived hepatic organoids |
| title_fullStr | Integrative analysis of single-cell RNA-seq and ATAC-seq reveals heterogeneity of induced pluripotent stem cell-derived hepatic organoids |
| title_full_unstemmed | Integrative analysis of single-cell RNA-seq and ATAC-seq reveals heterogeneity of induced pluripotent stem cell-derived hepatic organoids |
| title_short | Integrative analysis of single-cell RNA-seq and ATAC-seq reveals heterogeneity of induced pluripotent stem cell-derived hepatic organoids |
| title_sort | integrative analysis of single cell rna seq and atac seq reveals heterogeneity of induced pluripotent stem cell derived hepatic organoids |
| topic | Molecular mechanism of gene regulation Integrative aspects of cell biology Experimental models in systems biology Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223017522 |
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