Evidence map›Paper›PMID 35313986›Full record

ArticleStem cell research & therapy2022

Characteristics of SOX9-positive progenitor-like cells during cholestatic liver regeneration in biliary atresia.

Yuting Lin, Fang Zhang, Ludi Zhang, Lian Chen, Shan Zheng

Abstract read
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Article in Stem cell research & therapy, 2022. 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

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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

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3 · Its place in the literature

Who cites it

14 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Dynamic activation and dual roles of SOX9Frontiers in cell and developmental biology · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
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  12. Review
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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Yuting Lin *Department of Pediatric Surgery, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, 399 Wan Yuan Road, Shanghai, 201102, China.
Fang Zhang *State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
Ludi ZhangState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
Lian ChenDepartment of Pathology, Children's Hospital of Fudan University, National Children's Medical Center, 399 Wan Yuan Road, Shanghai, 201102, China.
Shan ZhengDepartment of Pediatric Surgery, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, 399 Wan Yuan Road, Shanghai, 201102, China. szheng@shmu.edu.cn.ORCID 0000-0002-9712-4573

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe progression of Biliary Atresia (BA) is associated with the number of reactive ductular cells (RDCs) whose heterogeneity in origin and evolution in humans remains unknown. SOX9-positive liver progenitor-like cells (LPLCs) have been shown to participate in RDCs and new hepatocyte formation during cholestatic liver regeneration in an animal model, which implies the possibility that hepatocyte-reprogrammed LPLCs could be a source of RDCs in BA. The present study aimed to elucidate the characteristics of SOX9-positive LPLCs in BA for exploring new possible therapeutic targets by manipulating the bi-differentiation process of LPLCs to prevent disease progression.

methodsTwenty-eight patients, including 24 patients with BA and 4 patients with Congenital Choledochal Cyst as the control group, were retrospectively recruited. Liver biopsy samples were classified histologically using a 4-point scale based on fibrosis severity. LPLCs were detected by SOX9 and HNF4A double positive staining. Single immunohistochemistry, double immunohistochemistry, and multiple immunofluorescence staining were used to determine the different cell types and characteristics of LPLCs.

resultsThe prognostic predictors of BA, namely total bile acid (TBA), RDCs, and fibrosis, were correlated to the emergence of LPLCs. SOX9 and HNF4A double-positive LPLCs co-stained rarely with relevant markers of portal hepatic progenitor cells (portal-HPCs), including CK19, CK7, EPCAM, PROM1 (CD133), TROP2, and AFP. Under cholestasis conditions, LPLCs acquired superior proliferation and anti-senescence ability among hepatocytes. Moreover, LPLCs arranged as a pseudo-rosette structure appeared from the periportal parenchyma to the portal region, which implied the differentiation from hepatocyte-reprogrammed LPLCs to RDCs with the progression of cholestasis.

conclusionsLPLCs are associated with disease progression and prognostic factors of BA. The bipotent characteristics of LPLCs are different from those of portal-HPCs. As cholestasis progresses, LPLCs appear to gain superior proliferation and anti-senescence ability and continually differentiate to RDCs.

Indexed as

Biliary AtresiaCholestasisSOX9 Transcription FactorHumansLiverLiver RegenerationRetrospective StudiesSOX9 protein, humanSOX9 Transcription FactorBiliary atresiaHepatic progenitor cellsLiver progenitor-like cellsReactive ductular cellsSOX9

Identifiers

PMID35313986
PMCPMC8935712

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