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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Autores principales:	Qian Zhang, Zhen Huang, Huanyan Zuo, Yuxiu Lin, Yao Xiao, Yanan Yan, Yu Cui, Chujiao Lin, Fei Pei, Zhi Chen, Huan Liu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	tooth development odontogenesis dental mesenchymal stem cells transcription factors epigenetics H3K27ac Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9fe09b4540d44cbfa33cca7a23a465d3
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spelling	oai:doaj.org-article:9fe09b4540d44cbfa33cca7a23a465d32021-11-30T22:16:33ZChromatin Accessibility Predetermines Odontoblast Terminal Differentiation2296-634X10.3389/fcell.2021.769193https://doaj.org/article/9fe09b4540d44cbfa33cca7a23a465d32021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.769193/fullhttps://doaj.org/toc/2296-634XEmbryonic 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.Qian ZhangZhen HuangHuanyan ZuoYuxiu LinYao XiaoYanan YanYu CuiChujiao LinFei PeiZhi ChenHuan LiuHuan LiuFrontiers Media S.A.articletooth developmentodontogenesisdental mesenchymal stem cellstranscription factorsepigeneticsH3K27acBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tooth development odontogenesis dental mesenchymal stem cells transcription factors epigenetics H3K27ac Biology (General) QH301-705.5
spellingShingle	tooth development odontogenesis dental mesenchymal stem cells transcription factors epigenetics H3K27ac Biology (General) QH301-705.5 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
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.
format	article
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
title	Chromatin Accessibility Predetermines Odontoblast Terminal Differentiation
title_short	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_sort	chromatin accessibility predetermines odontoblast terminal differentiation
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/9fe09b4540d44cbfa33cca7a23a465d3
work_keys_str_mv	AT qianzhang chromatinaccessibilitypredeterminesodontoblastterminaldifferentiation AT zhenhuang chromatinaccessibilitypredeterminesodontoblastterminaldifferentiation AT huanyanzuo chromatinaccessibilitypredeterminesodontoblastterminaldifferentiation AT yuxiulin chromatinaccessibilitypredeterminesodontoblastterminaldifferentiation AT yaoxiao chromatinaccessibilitypredeterminesodontoblastterminaldifferentiation AT yananyan chromatinaccessibilitypredeterminesodontoblastterminaldifferentiation AT yucui chromatinaccessibilitypredeterminesodontoblastterminaldifferentiation AT chujiaolin chromatinaccessibilitypredeterminesodontoblastterminaldifferentiation AT feipei chromatinaccessibilitypredeterminesodontoblastterminaldifferentiation AT zhichen chromatinaccessibilitypredeterminesodontoblastterminaldifferentiation AT huanliu chromatinaccessibilitypredeterminesodontoblastterminaldifferentiation AT huanliu chromatinaccessibilitypredeterminesodontoblastterminaldifferentiation
_version_	1718406281757196288

Chromatin Accessibility Predetermines Odontoblast Terminal Differentiation

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