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Chromatin Accessibility Predetermines Odontoblast Terminal Differentiation.

Qian Zhang1, Zhen Huang2, Huanyan Zuo1

  • 1The 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, China.

Frontiers in Cell and Developmental Biology
|December 13, 2021
PubMed
Summary

Chromatin accessibility changes dynamically during odontoblast differentiation, revealing key regulatory elements and transcription factor roles in dentinogenesis and regeneration.

Keywords:
H3K27acRNA-seqchromatin immunoprecipitation sequencingdental mesenchymal stem cellsepigeneticsodontogenesistooth developmenttranscription factors

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Genetics and Epigenetics

Background:

  • Embryonic development and stem cell differentiation involve dynamic transcriptional factor binding and chromatin modifications.
  • Odontoblast differentiation, crucial for dentinogenesis, originates from cranial neural crest cells.
  • The role of chromatin accessibility in odontoblast terminal differentiation was previously unclear.

Purpose of the Study:

  • To investigate the impact of chromatin accessibility on odontoblast terminal differentiation.
  • To map open chromatin regulatory elements during dentinogenesis.
  • To understand the regulation of these elements by transcription factor families.

Main Methods:

  • Integration of single-cell RNA-seq and bulk RNA-seq.
  • Chromatin accessibility analysis using ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing).
  • Histone modification analysis using H3K27Ac CUT and Tag.
  • Time-course ATAC-seq experiments.

Main Results:

  • In vitro odontoblast differentiation mirrored natural crown odontoblast development.
  • Chromatin regions near odontogenic genes were accessible before induction, while regions near mineralization genes became accessible post-induction.
  • Gene expression correlated with chromatin accessibility, and odontoblast terminal differentiation was linked to basic region/leucine zipper (bZIP) transcription factor family binding, with ATF5 validated in vitro.

Conclusions:

  • This study provides a comprehensive map of open chromatin during dentinogenesis.
  • Dynamic regulation of chromatin accessibility by transcription factors drives odontoblast terminal differentiation.
  • Findings offer insights into the genetic regulation of dentin regeneration using dental mesenchymal stem cells.