Spatiotemporal role of SETD2-H3K36me3 in murine pancreatic organogenesis
Summary: Pancreas development is tightly controlled by multilayer mechanisms. Despite years of effort, large gaps remain in understanding how histone modifications coordinate pancreas development. SETD2, a predominant histone methyltransferase of H3K36me3, plays a key role in embryonic stem cell dif...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724000317 |
| _version_ | 1797291800617025536 |
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| author | Ping Lu Junyi Xu Xuqing Shen Jiajun Sun Mingzhu Liu Ningning Niu Qidi Wang Jing Xue |
| author_facet | Ping Lu Junyi Xu Xuqing Shen Jiajun Sun Mingzhu Liu Ningning Niu Qidi Wang Jing Xue |
| author_sort | Ping Lu |
| collection | DOAJ |
| description | Summary: Pancreas development is tightly controlled by multilayer mechanisms. Despite years of effort, large gaps remain in understanding how histone modifications coordinate pancreas development. SETD2, a predominant histone methyltransferase of H3K36me3, plays a key role in embryonic stem cell differentiation, whose role in organogenesis remains elusive. Here, by combination of cleavage under targets and tagmentation (CUT&Tag), assay for transposase-accessible chromatin using sequencing (ATAC-seq), and bulk RNA sequencing, we show a dramatic increase in the H3K36me3 level from the secondary transition phase and decipher the related transcriptional alteration. Using single-cell RNA sequencing, we define that pancreatic deletion of Setd2 results in abnormalities in both exocrine and endocrine lineages: hyperproliferative tip progenitor cells lead to abnormal differentiation; Ngn3+ endocrine progenitors decline due to the downregulation of Nkx2.2, leading to insufficient endocrine development. Thus, these data identify SETD2 as a crucial player in embryonic pancreas development, providing a clue to understanding the dysregulation of histone modifications in pancreatic disorders. |
| first_indexed | 2024-03-07T19:42:58Z |
| format | Article |
| id | doaj.art-e5023989db154b9bbce416c1d486e698 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-07T19:42:58Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-e5023989db154b9bbce416c1d486e6982024-02-29T05:18:42ZengElsevierCell Reports2211-12472024-02-01432113703Spatiotemporal role of SETD2-H3K36me3 in murine pancreatic organogenesisPing Lu0Junyi Xu1Xuqing Shen2Jiajun Sun3Mingzhu Liu4Ningning Niu5Qidi Wang6Jing Xue7State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding authorStem Cell Research Center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaStem Cell Research Center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaStem Cell Research Center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaStem Cell Research Center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Sino-French Research Center for Life Sciences and Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding authorState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Stem Cell Research Center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding authorSummary: Pancreas development is tightly controlled by multilayer mechanisms. Despite years of effort, large gaps remain in understanding how histone modifications coordinate pancreas development. SETD2, a predominant histone methyltransferase of H3K36me3, plays a key role in embryonic stem cell differentiation, whose role in organogenesis remains elusive. Here, by combination of cleavage under targets and tagmentation (CUT&Tag), assay for transposase-accessible chromatin using sequencing (ATAC-seq), and bulk RNA sequencing, we show a dramatic increase in the H3K36me3 level from the secondary transition phase and decipher the related transcriptional alteration. Using single-cell RNA sequencing, we define that pancreatic deletion of Setd2 results in abnormalities in both exocrine and endocrine lineages: hyperproliferative tip progenitor cells lead to abnormal differentiation; Ngn3+ endocrine progenitors decline due to the downregulation of Nkx2.2, leading to insufficient endocrine development. Thus, these data identify SETD2 as a crucial player in embryonic pancreas development, providing a clue to understanding the dysregulation of histone modifications in pancreatic disorders.http://www.sciencedirect.com/science/article/pii/S2211124724000317CP: Developmental biology |
| spellingShingle | Ping Lu Junyi Xu Xuqing Shen Jiajun Sun Mingzhu Liu Ningning Niu Qidi Wang Jing Xue Spatiotemporal role of SETD2-H3K36me3 in murine pancreatic organogenesis Cell Reports CP: Developmental biology |
| title | Spatiotemporal role of SETD2-H3K36me3 in murine pancreatic organogenesis |
| title_full | Spatiotemporal role of SETD2-H3K36me3 in murine pancreatic organogenesis |
| title_fullStr | Spatiotemporal role of SETD2-H3K36me3 in murine pancreatic organogenesis |
| title_full_unstemmed | Spatiotemporal role of SETD2-H3K36me3 in murine pancreatic organogenesis |
| title_short | Spatiotemporal role of SETD2-H3K36me3 in murine pancreatic organogenesis |
| title_sort | spatiotemporal role of setd2 h3k36me3 in murine pancreatic organogenesis |
| topic | CP: Developmental biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724000317 |
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