Chromatin accessibility dynamics during kidney organoid induction from human embryonic stem cells.
5 affiliations
- 1Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institute, Department of nephrology,, The Fifth Affiliated Hospital of Guangzhou Medical University；Guangzhou National Laboratory, Guangzhou, Guangdong, China.
- 2Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, Henan, China.
- 3School of Biosciences & Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
- 4Laboratory of Cell Fate Control, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China. [email protected].
- 5Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institute, Department of nephrology,, The Fifth Affiliated Hospital of Guangzhou Medical University；Guangzhou National Laboratory, Guangzhou, Guangdong, China. [email protected].
Abstract
Human kidney development remains incompletely characterized at the level of chromatin accessibility. Here, we investigate chromatin accessibility dynamics (CAD) during the differentiation of human embryonic stem cells (hESCs) into kidney organoids (E-iKOs). Time-course ATAC-seq reveals progressive remodeling of pluripotency-associated chromatin landscapes toward an intermediate mesoderm state, followed by metanephric mesenchyme specification and early nephron epithelialization. These transitions are accompanied by increased accessibility at genomic regions enriched for binding motifs of transcription factors, including SIX, HOX, LHX, PAX, EBF, RFX, WT1, HNF1B, and TEAD. Functional analyses demonstrate that HNF1β is required for tubular differentiation, as HNF1β deficiency results in severe defects in tubule formation while podocytes remain detectable. Integrative analysis of chromatin accessibility and time-course transcriptomics further identifies the histone H3K79 methyltransferase DOT1L as a regulator required for nephron progenitor induction and epithelial differentiation. DOT1L deficiency is associated with widespread alterations in chromatin accessibility and gene expression, particularly at regions enriched for SIX, HOX, PAX, EBF, WT1, HNF1B, and TEAD motifs, accompanied by impaired mesenchymal-to-epithelial transition. Together, this study provides a valuable resource describing chromatin accessibility dynamics during human kidney organoid differentiation and a foundation for future studies of human nephrogenesis in vitro.
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BibTeX
@article{chen2026chromatin,
title = {{Chromatin accessibility dynamics during kidney organoid induction from human embryonic stem cells.}},
author = {Huan Chen and Yapei Yuan and Baomei Cai and Sihua Ou and Ruifang Zhang and Yiyi Cheng and Chunhua Zhou and Yudong Fu and Sihao Chen and Yingxiu Chen and Ziyu Feng and Yunjing Du and Wei He and Shengyong Yu and Mengjie Pan and Yuehong Yan and Dajiang Qin and Duanqing Pei and Shangtao Cao},
journal = {Cell \& bioscience},
year = {2026},
month = aug,
doi = {10.1186/s13578-026-01628-6},
url = {https://europepmc.org/article/MED/42958463},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Chromatin accessibility dynamics during kidney organoid induction from human embryonic stem cells.
AU - Huan Chen
AU - Yapei Yuan
AU - Baomei Cai
AU - Sihua Ou
AU - Ruifang Zhang
AU - Yiyi Cheng
AU - Chunhua Zhou
AU - Yudong Fu
AU - Sihao Chen
AU - Yingxiu Chen
AU - Ziyu Feng
AU - Yunjing Du
AU - Wei He
AU - Shengyong Yu
AU - Mengjie Pan
AU - Yuehong Yan
AU - Dajiang Qin
AU - Duanqing Pei
AU - Shangtao Cao
PY - 2026
DA - 2026/08/04
JO - Cell & bioscience
DO - 10.1186/s13578-026-01628-6
UR - https://europepmc.org/article/MED/42958463
AB - Human kidney development remains incompletely characterized at the level of chromatin accessibility. Here, we investigate chromatin accessibility dynamics (CAD) during the differentiation of human embryonic stem cells (hESCs) into kidney organoids (E-iKOs). Time-course ATAC-seq reveals progressive remodeling of pluripotency-associated chromatin landscapes toward an intermediate mesoderm state, followed by metanephric mesenchyme specification and early nephron epithelialization. These transitions are accompanied by increased accessibility at genomic regions enriched for binding motifs of transcription factors, including SIX, HOX, LHX, PAX, EBF, RFX, WT1, HNF1B, and TEAD. Functional analyses demonstrate that HNF1β is required for tubular differentiation, as HNF1β deficiency results in severe defects in tubule formation while podocytes remain detectable. Integrative analysis of chromatin accessibility and time-course transcriptomics further identifies the histone H3K79 methyltransferase DOT1L as a regulator required for nephron progenitor induction and epithelial differentiation. DOT1L deficiency is associated with widespread alterations in chromatin accessibility and gene expression, particularly at regions enriched for SIX, HOX, PAX, EBF, WT1, HNF1B, and TEAD motifs, accompanied by impaired mesenchymal-to-epithelial transition. Together, this study provides a valuable resource describing chromatin accessibility dynamics during human kidney organoid differentiation and a foundation for future studies of human nephrogenesis in vitro.
SN - 2045-3701
ER -