Evidence map›Paper›PMID 40670531›Full record

ArticleScientific reports2025

Expression of DNAJB1-PRKACA oncogene suppresses the differentiation potential of liver progenitor organoids towards a hepatocyte lineage.

Emma DiPietro, Nihal Bharath, Michael Karski, Olivia Durfee, Marc S Sherman, Qianyi Ma, Liang Sun, Alaa R Farghli, Colton J Smith, Ina Kycia and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. 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
–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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
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

14 authors.

Emma DiPietro *Department of Surgery, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
Nihal Bharath *Department of Surgery, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
Michael KarskiDepartment of Surgery, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
Olivia DurfeeDepartment of Surgery, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
Marc S ShermanDivision of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Qianyi MaResearch Computing, Department of Information Technology, Boston Children's Hospital, Boston, MA, USA.
Liang SunResearch Computing, Department of Information Technology, Boston Children's Hospital, Boston, MA, USA.
Alaa R FarghliDepartment of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Colton J SmithDivision of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Ina KyciaDepartment of Surgery, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
Praveen SethupathyDepartment of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Wolfram GoesslingDivision of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Michael S RogersDepartment of Surgery, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
Khashayar VakiliDepartment of Surgery, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA. khashayar.vakili@childrens.harvard.edu.

Funding

Dysregulation of the unfolded protein response in the pathogenesis of non-alcoholic steatohepatitisK08DK139370 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MARC S SHERMAN · 2025 to 2026
$342k
NIDDK NIH HHS K08 DK139370
6 · The paper itself

Abstract

Fibrolamellar carcinoma (FLC) is a type of primary liver cancer that predominantly affects healthy adolescents and young adults in a background of normal liver. The DNAJB1-PRKACA fusion gene is an oncogenic driver in FLC tumors. To investigate the oncogenic mechanisms of this fusion gene, we developed a model using human liver progenitor organoids engineered to express DNAJB1-PRKACA. Single-nucleus RNA sequencing of these organoids revealed an upregulation of genes that significantly overlap with those expressed in FLC epithelial cells. Additionally, the expression of DNAJB1-PRKACA led to the downregulation of genes coding for markers of mature epithelial cells, indicating a shift toward a less differentiated state. When compared to wild-type liver progenitor organoids, which exhibit a strong ability to differentiate into hepatocytes, the DNAJB1-PRKACA-expressing liver progenitor organoids displayed a markedly reduced capacity for hepatocyte differentiation. These findings suggest that the DNAJB1-PRKACA fusion gene disrupts the normal differentiation process of liver progenitor cells.

Indexed as

Carcinoma, HepatocellularCell DifferentiationCyclic AMP-Dependent Protein Kinase Catalytic SubunitsHepatocytesHSP40 Heat-Shock ProteinsLiverLiver NeoplasmsOncogene Proteins, FusionOrganoidsStem CellsCell LineageHumansCyclic AMP-Dependent Protein Kinase Catalytic SubunitsDNAJB1 protein, humanHSP40 Heat-Shock ProteinsOncogene Proteins, FusionPRKACA protein, human

Identifiers

PMID40670531
PMCPMC12267505

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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.