Evidence map›Paper›PMID 34112239›Full record

ArticleStem cell research & therapy2021

The stemness of hepatocytes is maintained by high levels of lipopolysaccharide via YAP1 activation.

Changchun Shao, Xue Yang, Yingying Jing, Xiaojuan Hou, Yihua Huang, Chen Zong, Lu Gao, Wenting Liu, Jinghua Jiang, Fei Ye and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 30% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
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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

15 authors at 4 institutions in 1 country.

Changchun Shao *Tumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China.
Xue Yang *Tumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China.
Yingying JingInstitute of Translational Medicine, Shanghai University, Shanghai, 200444, China.
Xiaojuan HouTumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China.
Yihua HuangDepartment of Pathology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, China.
Chen ZongTumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China.
Lu GaoTumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China.
Wenting LiuTumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China.
Jinghua JiangTumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China.
Fei YeTumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China.
Junxia ShiTumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China.
Qiudong ZhaoTumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China.
Rong LiTumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China.
Xiaoren ZhangAffiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, State Key Laboratory of Respiratory Disease, Guangzhou, 510000, China. xrzhang@sibs.ac.cn.
Lixin WeiTumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China. weilixin_smmu@163.com.
Second Military Medical University · CNFujian Medical University · CNGuangzhou Medical University · CNShanghai University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe liver possesses a powerful regeneration ability, which is correlated with the stemness of hepatocytes in the portal vein (PV). However, the mechanism underlying the maintenance of hepatocyte stemness has not been elucidated. Here, we hypothesized that high levels of lipopolysaccharide from the portal vein might maintain the stemness of hepatocytes in the PV area.

methodsFirst, we examined the location of hepatic stem cells and the concentration of lipopolysaccharide (LPS) in the portal vein and inferior vena cava. Then, we assessed the effect of LPS on stemness maintenance in mice by using antibiotics to eliminate LPS and knocking out the LPS receptor, TLR4. In vitro, the effect of LPS on the stemness of hepatocytes was investigated by colony and sphere formation assays and assessment of pluripotent and stem cell marker expression. Furthermore, we studied the mechanism by which LPS regulates the stemness of hepatocytes. Finally, we ligated the portal vein branch to further verify the effect of LPS.

resultsWe found that a high level of LPS from the portal vein was correlated with the location of hepatic stem cells in the PV area, and elimination of LPS by antibiotics inhibited the expression of the stemness marker. LPS promoted colony and sphere formation and induced the upregulation of pluripotent and stem cell markers in AML12 cells. Furthermore, in the reprogramming medium, LPS facilitated the dedifferentiation of mature hepatocytes into hepatic progenitor-like cells, which exhibited a bipotent differentiation capacity in vivo and in vitro. Mechanistically, LPS bound TLR4 to regulate stemness of hepatocytes via the activation of YAP1 signaling, and blockade of YAP1 abolished the LPS-induced cell stemness and upregulation of pluripotent markers.

conclusionsOur study implies a correlation between LPS/TLR4/YAP1 signaling and cell stemness, and LPS was shown to be involved in stemness maintenance of hepatocytes in the PV area. LPS might be used to induce the dedifferentiation of mature hepatocytes into progenitor-like cells for repair of liver injury.

Indexed as

HepatocytesLipopolysaccharidesAnimalsLiverMiceSignal TransductionStem CellsLipopolysaccharidesHepatocytesLipopolysaccharideStemness maintenanceToll-like receptor 4Yes-associated protein 1

Identifiers

PMID34112239
PMCPMC8193885
OpenAlexW3172982865

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.