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Updated: Dec 23, 2025

An Ex vivo Culture System to Study Thyroid Development
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Epigenetic Changes During Human Thyroid Cell Differentiation.

Risheng Ma1, Syed Morshed1, Rauf Latif1

  • 1Thyroid Research Unit, Department of Medicine, The Icahn School of Medicine at Mount Sinai, The James J. Peters VA Medical Center, New York, New York, USA.

Thyroid : Official Journal of the American Thyroid Association
|April 30, 2020
PubMed
Summary
This summary is machine-generated.

Ethacridine activates thyroid cell differentiation in human embryonic stem cells by increasing chromatin accessibility and histone acetylation. This epigenetic reprogramming promotes the expression of key genes for thyroid follicular cell development.

Keywords:
ATAC-seqNKX2-1PAX8TAZacetyl histone H4acetylation of histone H4 at lysine 16epigenetic modificationhuman embryonic stem cellsthyroid

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Area of Science:

  • Stem Cell Biology
  • Epigenetics
  • Endocrinology

Background:

  • Transcription factors TAZ, PAX8, and NKX2-1 are crucial for thyroid cell development and function.
  • TAZ enhances the activity of PAX8, NKX2-1, and thyroglobulin (TG) gene expression, indicating its role in thyroid cell speciation.
  • Ethacridine, a TAZ activator, can induce thyroid-specific transcription in human embryonic stem cell (hES)-derived endodermal cells.

Purpose of the Study:

  • To investigate the epigenetic modifications in the promoter regions of key thyroid transcription factors during in vitro differentiation of hES cells into thyrocytes.
  • To understand the role of ethacridine in regulating these epigenetic changes for thyroid cell differentiation.

Main Methods:

  • Assay for Transposase Accessible Chromatin sequencing (ATAC-seq) to profile chromatin accessibility.
  • Bisulfite sequencing to examine DNA methylation.
  • Chromatin immunoprecipitation polymerase chain reaction (ChIP-PCR) assays to assess histone acetylation (H4K16ac).

Main Results:

  • ATAC-seq revealed increased chromatin accessibility of TAZ, NKX2-1, and PAX8 promoters upon treatment with activin A and ethacridine.
  • No significant changes in DNA methylation were observed in the promoters of these transcription factors.
  • Histone H4 acetylation, specifically at lysine 16, was detected in the promoters, correlating with the expression of thyroid-specific genes (NKX2-1, PAX8, NIS, TSHR, TG).

Conclusions:

  • Ethacridine treatment enhances chromatin accessibility and histone H4 acetylation in hES cell-derived endodermal cells.
  • These epigenetic changes facilitate the activation of genes essential for the speciation of thyroid follicular cells.
  • The findings highlight a mechanism for directed differentiation of hES cells into functional thyrocytes using small molecule activators.