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Peer-reviewedCC BY-NC-NDNature communications

A temporal single cell atlas of dynamic chromatin accessibility during murine lung maturation.

6 affiliations
  1. 1Department of Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
  2. 2Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
  3. 3Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China.
  4. 4Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
  5. 5Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. [email protected].
  6. 6Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. [email protected].

Abstract

Lung maturation involves intricate cellular differentiation and structural remodeling, yet the underlying epigenetic dynamics remain poorly characterized at single-cell resolution. Here we present HTL-ATAC-seq, an ultra-high-throughput, ligation-based single-cell ATAC-seq approach. Applying HTL-ATAC-seq to mouse lung tissue across 15 continuous postnatal time points, we construct a temporal chromatin accessibility atlas of 1,185,619 nuclei, identifying 129 distinct cell subclusters and 713,987 candidate chromatin regulatory elements. Temporal analysis reveals three distinct cellular maturation stages and 12 dynamic chromatin accessibility patterns, capturing the transition from structural morphogenesis to immune maturation. We uncover distinct transcription factor regulatory patterns between alveolar type 1 and 2 cells and identify a putative Sprr1a enhancer specifically active in alveolar type 1 cells. Finally, we identify time- and cell-type-specific cis-regulatory elements associated with lung disease-related gene sets. In this work, we provide a comprehensive resource for understanding the epigenetic mechanisms underlying lung maturation and lung disease-associated regulatory programs.

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BibTeX
@article{wang2026temporal,
  title = {{A temporal single cell atlas of dynamic chromatin accessibility during murine lung maturation.}},
  author = {Xin Wang and Yuhao Deng and Yanru Zhang and Yurong Chen and Hang Li and Min Zhang and Zhizhuo Cao and Shaojun Zhang and Fang Wang},
  journal = {Nature communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77870-w},
  url = {https://europepmc.org/article/MED/42901895},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - A temporal single cell atlas of dynamic chromatin accessibility during murine lung maturation.
AU  - Xin Wang
AU  - Yuhao Deng
AU  - Yanru Zhang
AU  - Yurong Chen
AU  - Hang Li
AU  - Min Zhang
AU  - Zhizhuo Cao
AU  - Shaojun Zhang
AU  - Fang Wang
PY  - 2026
DA  - 2026/09/18
JO  - Nature communications
DO  - 10.1038/s41467-026-77870-w
UR  - https://europepmc.org/article/MED/42901895
AB  - Lung maturation involves intricate cellular differentiation and structural remodeling, yet the underlying epigenetic dynamics remain poorly characterized at single-cell resolution. Here we present HTL-ATAC-seq, an ultra-high-throughput, ligation-based single-cell ATAC-seq approach. Applying HTL-ATAC-seq to mouse lung tissue across 15 continuous postnatal time points, we construct a temporal chromatin accessibility atlas of 1,185,619 nuclei, identifying 129 distinct cell subclusters and 713,987 candidate chromatin regulatory elements. Temporal analysis reveals three distinct cellular maturation stages and 12 dynamic chromatin accessibility patterns, capturing the transition from structural morphogenesis to immune maturation. We uncover distinct transcription factor regulatory patterns between alveolar type 1 and 2 cells and identify a putative Sprr1a enhancer specifically active in alveolar type 1 cells. Finally, we identify time- and cell-type-specific cis-regulatory elements associated with lung disease-related gene sets. In this work, we provide a comprehensive resource for understanding the epigenetic mechanisms underlying lung maturation and lung disease-associated regulatory programs.
SN  - 2041-1723
ER  -