Evidence map›Paper›PMID 37173651›Full record

ArticleBMC genomics2023

Integration of ATAC-Seq and RNA-Seq reveals FOSL2 drives human liver progenitor-like cell aging by regulating inflammatory factors.

Min Ding, Weijian Huang, Guifen Liu, Bo Zhai, Hexin Yan, Yong Zhang

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 10% of its field
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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
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  10. Echinocandin Adaptation inJournal of fungi (Basel, Switzerland) · 2025
    Article
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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

6 authors at 2 institutions in 1 country.

Min Ding *Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
Weijian Huang *Department of Anesthesiology and Critical Care Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China.
Guifen LiuInstitute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
Bo ZhaiDepartment of Interventional Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China. zhaiboshi@sina.com.
Hexin YanDepartment of Interventional Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China. hexinyw@163.com.
Yong ZhangInstitute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China. yzhang@tongji.edu.cn.
Shanghai East Hospital · CNRenji Hospital · CN

Funding

General programs of the National Natural Science Foundation of China 31872823General programs of the National Natural Science Foundation of China 82070619National Key Research and Development Program of China 2018YFA0108200the State Key Laboratory of Oncogenes and Related Genes No.91-17-33
6 · The paper itself

Abstract

backgroundHuman primary hepatocytes (PHCs) are considered to be the best cell source for cell-based therapies for the treatment of end-stage liver disease and acute liver failure. To obtain sufficient and high-quality functional human hepatocytes, we have established a strategy to dedifferentiate human PHCs into expandable hepatocyte-derived liver progenitor-like cells (HepLPCs) through in vitro chemical reprogramming. However, the reduced proliferative capacity of HepLPCs after long-term culture still limits their utility. Therefore, in this study, we attempted to explore the potential mechanism related to the proliferative ability of HepLPCs in vitro culture.

resultsIn this study, analysis of assay for transposase accessible chromatin using sequencing (ATAC-seq) and RNA sequencing (RNA-seq) were performed for PHCs, proliferative HepLPCs (pro-HepLPCs) and late-passage HepLPCs (lp-HepLPCs). Genome-wide transcriptional and chromatin accessibility changes during the conversion and long-term culture of HepLPCs were studied. We found that lp-HepLPCs exhibited an aged phenotype characterized by the activation of inflammatory factors. Epigenetic changes were found to be consistent with our gene expression findings, with promoter and distal regions of many inflammatory-related genes showing increased accessibility in the lp-HepLPCs. FOSL2, a member of the AP-1 family, was found to be highly enriched in the distal regions with increased accessibility in lp-HepLPCs. Its depletion attenuated the expression of aging- and senescence-associated secretory phenotype (SASP)-related genes and resulted in a partial improvement of the aging phenotype in lp-HepLPCs.

conclusionsFOSL2 may drive the aging of HepLPCs by regulating inflammatory factors and its depletion may attenuate this phenotypic shift. This study provides a novel and promising approach for the long-term in vitro culture of HepLPCs.

Indexed as

Cellular SenescenceChromatinChromatin Immunoprecipitation SequencingFos-Related Antigen-2High-Throughput Nucleotide SequencingHumansLiverRNA-SeqChromatinFOSL2 protein, humanFos-Related Antigen-2AgingATAC-seqHepLPCsInflammatory responseRNA-seq

Identifiers

PMID37173651
PMCPMC10182660
OpenAlexW4376629887

What OpenQuestion holds

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Registered trials

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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.