Evidence map›Paper›PMID 42469253›Full record

ArticleNature communications2026

Extracellular matrix stiffness directs region-specific lung epithelial differentiation revealed by hPSC-derived lung organoids.

Zhiying Liao, Hao Meng, Junjie Lv, Dong Wang, Hengrui Zhang, Runxi Jiang, Ruihao Lan, Yu Chen, Jiaqi Sun, Zonghong Li and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Zhiying Liao *School of Biomedical Engineering, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou, China.
Hao Meng *School of Biomedical Engineering, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou, China. meng_hao@gzlab.ac.cn.ORCID http://orcid.org/0000-0003-4647-6541
Junjie Lv *School of Biomedical Engineering, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou, China.
Dong WangGMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China.
Hengrui ZhangSchool of Biomedical Engineering, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou, China.
Runxi JiangSchool of Biomedical Engineering, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou, China.
Ruihao LanSchool of Biomedical Engineering, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou, China.
Yu ChenSchool of Biomedical Engineering, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou, China.
Jiaqi SunSchool of Biomedical Engineering, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou, China.
Zonghong LiSchool of Biomedical Engineering, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou, China.ORCID http://orcid.org/0000-0002-5153-0007
Xiangping YangGuangdong Key Provincial Laboratory of Allergy & Clinical Immunology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Xuepeng ChenSchool of Biomedical Engineering, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou, China. chen_xuepeng@gzlab.ac.cn.ORCID http://orcid.org/0000-0001-7316-6894
Jincun ZhaoSchool of Biomedical Engineering, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou, China. zhaojincun@gird.cn.ORCID http://orcid.org/0000-0003-2515-5589
Tao XuSchool of Biomedical Engineering, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou, China. xu_tao@gzlab.ac.cn.
Huisheng LiuSchool of Biomedical Engineering, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou, China. liu_huisheng@gzlab.ac.cn.ORCID http://orcid.org/0000-0001-5371-7943

Funding

Pearl River S and T Nova Program of Guangzhou (Pearl River S & T Nova Program of Guangzhou) 2021QN02Y572
6 · The paper itself

Abstract

Regional epithelial lineages of the human respiratory system reside within an extracellular matrix (ECM) whose mechanics vary along the airway-alveolar axis, yet how ECM stiffness directs epithelial fates remains unclear. Here, utilizing human pluripotent stem cell-derived lung organoids embedded in stiffness-tunable hydrogels as an in vitro model, we show ECM stiffness governs region-specific epithelial differentiation. Stepwise softening of ECM stiffness yields airway organoids with proximal-to-distal airway epithelial compositions and biomimetic physiological functions. During alveolar differentiation, increased stiffness promotes alveolar type 2 (AT2) and type 1 (AT1) maturation and drives AT2-to-AT1 transition. Furthermore, RNA sequencing reveals ECM stiffness regulates epithelial fates primarily through mechanotransduction pathways. Finally, these organoids reproduce the infection tropisms of SARS-CoV-2 variants. Together, this research elucidates ECM stiffness as a critical determinant of epithelial cell fate specification and region-specific lung organoid generation, which offers a valuable in vitro model for studying region-specific lung development, diseases pathogenesis, and drug screening.

Indexed as

Cell DifferentiationExtracellular MatrixLungOrganoidsPluripotent Stem CellsAlveolar Epithelial CellsEpithelial CellsHumansHydrogelsMechanotransduction, CellularSARS-CoV-2Hydrogels

Identifiers

PMID42469253
PMCPMC13493954

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.