Evidence map›Paper›PMID 38810140›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

Kidney Organoid Modeling of WT1 Mutations Reveals Key Regulatory Paths Underlying Podocyte Development.

Gang Wang, Hangdi Wu, Xiuwen Zhai, Li Zhang, Changming Zhang, Chen Cheng, Xiaodong Xu, Erzhi Gao, Xushen Xiong, Jin Zhang and 1 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

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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

11 authors.

Gang WangNational Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, 210002, China.
Hangdi WuDepartment of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.
Xiuwen ZhaiNational Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, 210002, China.
Li ZhangDepartment of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.
Changming ZhangNational Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, 210002, China.
Chen ChengDepartment of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.
Xiaodong XuNational Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, 210002, China.
Erzhi GaoNational Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, 210002, China.
Xushen XiongDepartment of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.
Jin ZhangDepartment of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.
Zhihong LiuNational Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, 210002, China.ORCID 0000-0001-6093-0726

Funding

National Key Research and Development Project of China 2021YFC2501302National Natural Science Foundation of China 32141004National Natural Science Foundation of China 32370609National Natural Science Foundation of China 82300800National Natural Science Foundation of China 82300835National Natural Science Foundation of China 92353301National Science Foundation for Post-doctoral Scientists of China 2023TQ0293Natural Science Foundation of Jiangsu Province BK20210150Zhejiang Provincial Natural Science Foundation of China LQ24H050001
6 · The paper itself

Abstract

Wilms tumor-1(WT1) is a crucial transcription factor that regulates podocyte development. However, the epigenomic mechanism underlying the function of WT1 during podocyte development has yet to be fully elucidated. Here, single-cell chromatin accessibility and gene expression maps of foetal kidneys and kidney organoids are generated. Functional implications of WT1-targeted genes, which are crucial for the development of podocytes and the maintenance of their structure, including BMPER/PAX2/MAGI2 that regulates WNT signaling pathway, MYH9 that maintains actin filament organization and NPHS1 that modulates cell junction assembly are identified. To further illustrate the functional importance of WT1-mediated transcriptional regulation during podocyte development, cultured and implanted patient-derived kidney organoids derived from the Induced Pluripotent Stem Cell (iPSCs) of a patient with a heterozygous missense mutation in WT1 are generated. Results from single-cell RNA sequencing (scRNA-seq) and functional assays confirm that the WT1 mutation leads to delays in podocyte development and causes damage to cell structures, due to its failure to activate the targeting genes MAGI2, MYH9, and NPHS1. Notably, correcting the mutation in the patient iPSCs using CRISPR-Cas9 gene editing rescues the podocyte phenotype. Collectively, this work elucidates the WT1-related epigenomic landscape with respect to human podocyte development and identifies the disease-causing role of a WT1 mutation.

Indexed as

OrganoidsPodocytesWT1 ProteinsHumansInduced Pluripotent Stem CellsKidneyMutationWT1 protein, humanWT1 Proteinskidney organoidpodocyte developmentscATAC‐seqscRNA‐seqWT1

Identifiers

PMID38810140
PMCPMC11304319

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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.