Evidence map›Paper›PMID 40973931›Full record

ArticleStem cell reviews and reports2026

CDX2 Promotes Hepatic Specification of hiPSC-derived Endoderm Through the PI3K-Akt-GSK3β Pathway for Improved Therapeutic Efficacy.

Fang Bai, Jinliang Duan, Daopeng Yang, Xingqiang Lai, Haibin Ji, Xiaofeng Zhu, Xiaoshun He, Anbin Hu

Abstract read
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Article in Stem cell reviews and reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  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

8 authors.

Fang BaiOrgan Transplant Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangdong, Guangzhou, China.
Jinliang DuanOrgan Transplant Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangdong, Guangzhou, China.
Daopeng YangOrgan Transplant Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangdong, Guangzhou, China.
Xingqiang LaiMaternal-Fetal Medicine Institute, Department of Obstetrics and Gynaecology, Shenzhen Baoan Women's and Children's Hospital, Shenzhen, Guangdong, China.
Haibin JiOrgan Transplant Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangdong, Guangzhou, China.
Xiaofeng ZhuOrgan Transplant Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangdong, Guangzhou, China.
Xiaoshun HeOrgan Transplant Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangdong, Guangzhou, China.
Anbin HuOrgan Transplant Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangdong, Guangzhou, China. huab@mail.sysu.edu.cn.

Funding

National Natural Science Foundation of China 81901514National Natural Science Foundation of China 82070635, 81672998Natural Science Foundation of Guangdong province of China 2019A1515011364, 2414050006208, 2514050002150Scientific and Technological Projects of Guangzhou City of China 2024B03J1250
6 · The paper itself

Abstract

BACKGROUND &

aimsHuman induced pluripotent stem cell (hiPSC)-derived hepatic endoderm (HE) is a potential treatment for liver diseases, but its heterogeneity poses challenges. Hepatic specification, the conversion of hiPSC-derived endoderm (DE) into HE, is critical for HE induction. Caudal homeobox transcription factor 2 (CDX2) regulates multiple signalling pathways during embryonic development and directs organogenesis. While CDX2 is a key regulator of organ development, its role during hepatic specification remains unclear.

methodsHE markers were detected using western blotting (WB) and immunofluorescence (IF). The CDX2 regulatory axis was identified using mRNA-seq and bioinformatics analysis. During hepatic specification, the relative pathways PI3K-AKT, WNT, epithelial‒mesenchymal transition (EMT) and extracellular matrix (ECM) were confirmed using WB. Hepatocyte-like functions were evaluated based on glycogen content, indocyanine green (ICG) uptake and albumin levels. The therapeutic efficacy of HE cells was evaluated in a mouse liver injury model.

resultsOverexpression of CDX2 resulted in enhanced expression and function of HE markers during hepatic specification. mRNA-seq and bioinformatics analysis revealed differentially expressed genes following CDX2 overexpression that target the PI3K-AKT and WNT pathways, which was confirmed by WB. Furthermore, the results showed that EMT and the ECM degradation were suppressed by CDX2 overexpression (p < 0.05). In addition, SB-3CT, an matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) inhibitor, effectively promoted the formation of HE cells derived from hiPSC-DEs. Functionally, hepatocyte-like cells derived from HE cells through CDX2 overexpression presented increased glycogen levels, ICG uptake and albumin production. On the other hand, liver functions and acute injuries were significantly ameliorated when CDX2-modulated HE cells were transplanted into a mouse model.

conclusionsCDX2 promotes HE formation through inhibition of the PI3K-Akt and Wnt/β-catenin pathways, as well as suppression of EMT and ECM degradation. Moreover, transplantation of CDX2-modulated HE cells represents an effective therapeutic approach for liver injury treatment.

Indexed as

CDX2 Transcription FactorEndodermGlycogen Synthase Kinase 3 betaInduced Pluripotent Stem CellsLiverPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktAnimalsCell DifferentiationEpithelial-Mesenchymal TransitionHepatocytesHumansMiceSignal TransductionCDX2 protein, humanCDX2 Transcription FactorGlycogen Synthase Kinase 3 betaPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktCDX2Hepatic endodermHepatic specificationLiver injuryPI3K–Akt–GSK3β

Identifiers

PMID40973931

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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.