Chromatin Accessibility Predetermines Odontoblast Terminal Differentiation
Embryonic development and stem cell differentiation are orchestrated by changes in sequential binding of regulatory transcriptional factors to their motifs. These processes are invariably accompanied by the alternations in chromatin accessibility, conformation, and histone modification. Odontoblast...
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.769193/full |
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| author | Qian Zhang Zhen Huang Huanyan Zuo Yuxiu Lin Yao Xiao Yanan Yan Yu Cui Chujiao Lin Fei Pei Zhi Chen Huan Liu Huan Liu |
| author_facet | Qian Zhang Zhen Huang Huanyan Zuo Yuxiu Lin Yao Xiao Yanan Yan Yu Cui Chujiao Lin Fei Pei Zhi Chen Huan Liu Huan Liu |
| author_sort | Qian Zhang |
| collection | DOAJ |
| description | Embryonic development and stem cell differentiation are orchestrated by changes in sequential binding of regulatory transcriptional factors to their motifs. These processes are invariably accompanied by the alternations in chromatin accessibility, conformation, and histone modification. Odontoblast lineage originates from cranial neural crest cells and is crucial in dentinogenesis. Our previous work revealed several transcription factors (TFs) that promote odontoblast differentiation. However, it remains elusive as to whether chromatin accessibility affects odontoblast terminal differentiation. Herein, integration of single-cell RNA-seq and bulk RNA-seq revealed that in vitro odontoblast differentiation using dental papilla cells at E18.5 was comparable to the crown odontoblast differentiation trajectory of OC (osteocalcin)-positive odontogenic lineage. Before in vitro odontoblast differentiation, ATAC-seq and H3K27Ac CUT and Tag experiments demonstrated high accessibility of chromatin regions adjacent to genes associated with odontogenic potential. However, following odontoblastic induction, regions near mineralization-related genes became accessible. Integration of RNA-seq and ATAC-seq results further revealed that the expression levels of these genes were correlated with the accessibility of nearby chromatin. Time-course ATAC-seq experiments further demonstrated that odontoblast terminal differentiation was correlated with the occupation of the basic region/leucine zipper motif (bZIP) TF family, whereby we validated the positive role of ATF5 in vitro. Collectively, this study reports a global mapping of open chromatin regulatory elements during dentinogenesis and illustrates how these regions are regulated via dynamic binding of different TF families, resulting in odontoblast terminal differentiation. The findings also shed light on understanding the genetic regulation of dentin regeneration using dental mesenchymal stem cells. |
| first_indexed | 2024-12-21T08:46:28Z |
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| id | doaj.art-9fe09b4540d44cbfa33cca7a23a465d3 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-21T08:46:28Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-9fe09b4540d44cbfa33cca7a23a465d32022-12-21T19:09:49ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-11-01910.3389/fcell.2021.769193769193Chromatin Accessibility Predetermines Odontoblast Terminal DifferentiationQian Zhang0Zhen Huang1Huanyan Zuo2Yuxiu Lin3Yao Xiao4Yanan Yan5Yu Cui6Chujiao Lin7Fei Pei8Zhi Chen9Huan Liu10Huan Liu11The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory for Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaFujian Key Laboratory of Developmental and Neuro Biology, College of Life Science, Fujian Normal University, Fuzhou, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory for Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory for Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory for Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaFujian Key Laboratory of Developmental and Neuro Biology, College of Life Science, Fujian Normal University, Fuzhou, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory for Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaDivision of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, United StatesThe State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory for Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory for Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory for Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaDepartment of Periodontology, School of Stomatology, Wuhan University, Wuhan, ChinaEmbryonic development and stem cell differentiation are orchestrated by changes in sequential binding of regulatory transcriptional factors to their motifs. These processes are invariably accompanied by the alternations in chromatin accessibility, conformation, and histone modification. Odontoblast lineage originates from cranial neural crest cells and is crucial in dentinogenesis. Our previous work revealed several transcription factors (TFs) that promote odontoblast differentiation. However, it remains elusive as to whether chromatin accessibility affects odontoblast terminal differentiation. Herein, integration of single-cell RNA-seq and bulk RNA-seq revealed that in vitro odontoblast differentiation using dental papilla cells at E18.5 was comparable to the crown odontoblast differentiation trajectory of OC (osteocalcin)-positive odontogenic lineage. Before in vitro odontoblast differentiation, ATAC-seq and H3K27Ac CUT and Tag experiments demonstrated high accessibility of chromatin regions adjacent to genes associated with odontogenic potential. However, following odontoblastic induction, regions near mineralization-related genes became accessible. Integration of RNA-seq and ATAC-seq results further revealed that the expression levels of these genes were correlated with the accessibility of nearby chromatin. Time-course ATAC-seq experiments further demonstrated that odontoblast terminal differentiation was correlated with the occupation of the basic region/leucine zipper motif (bZIP) TF family, whereby we validated the positive role of ATF5 in vitro. Collectively, this study reports a global mapping of open chromatin regulatory elements during dentinogenesis and illustrates how these regions are regulated via dynamic binding of different TF families, resulting in odontoblast terminal differentiation. The findings also shed light on understanding the genetic regulation of dentin regeneration using dental mesenchymal stem cells.https://www.frontiersin.org/articles/10.3389/fcell.2021.769193/fulltooth developmentodontogenesisdental mesenchymal stem cellstranscription factorsepigeneticsH3K27ac |
| spellingShingle | Qian Zhang Zhen Huang Huanyan Zuo Yuxiu Lin Yao Xiao Yanan Yan Yu Cui Chujiao Lin Fei Pei Zhi Chen Huan Liu Huan Liu Chromatin Accessibility Predetermines Odontoblast Terminal Differentiation Frontiers in Cell and Developmental Biology tooth development odontogenesis dental mesenchymal stem cells transcription factors epigenetics H3K27ac |
| title | Chromatin Accessibility Predetermines Odontoblast Terminal Differentiation |
| title_full | Chromatin Accessibility Predetermines Odontoblast Terminal Differentiation |
| title_fullStr | Chromatin Accessibility Predetermines Odontoblast Terminal Differentiation |
| title_full_unstemmed | Chromatin Accessibility Predetermines Odontoblast Terminal Differentiation |
| title_short | Chromatin Accessibility Predetermines Odontoblast Terminal Differentiation |
| title_sort | chromatin accessibility predetermines odontoblast terminal differentiation |
| topic | tooth development odontogenesis dental mesenchymal stem cells transcription factors epigenetics H3K27ac |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.769193/full |
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