Evidence map›Paper›PMID 39998949›Full record

ArticleCell reports2025

Identification of hepatocyte-primed cholangiocytes in the homeostatic liver by in vivo lentiviral gene transfer to mice and non-human primates.

Michela Milani, Francesco Starinieri, Anna Fabiano, Stefano Beretta, Tiziana Plati, Cesare Canepari, Mauro Biffi, Fabio Russo, Valeria Berno, Rossana Norata and 6 more

Abstract read
In one paragraph

Article in Cell reports, 2025. 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
  2. Article
  3. Review
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

16 authors.

Michela MilaniSan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Francesco StarinieriSan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Anna FabianoSan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Stefano BerettaSan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Tiziana PlatiSan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Cesare CanepariSan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Vita Salute San Raffaele University, 20132 Milan, Italy.
Mauro BiffiSan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Fabio RussoSan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Valeria BernoAdvanced Light and Electron Microscopy BioImaging Center (ALEMBIC), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Rossana NorataSan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Francesca SanvitoSan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Pathology Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Ivan MerelliInstitute for Biomedical Technologies, National Research Council, 20054 Segrate (MI), Italy.
Luigi AloiaThe Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK.
Meritxell HuchThe Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Luigi NaldiniSan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Vita Salute San Raffaele University, 20132 Milan, Italy.
Alessio CantoreSan Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Vita Salute San Raffaele University, 20132 Milan, Italy. Electronic address: cantore.alessio@hsr.it.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Liver regeneration is supported by hepatocytes and, in certain conditions, biliary epithelial cells (BECs). BECs are facultative liver stem cells that form organoids in culture and engraft in damaged livers. However, BEC heterogeneity in the homeostatic liver remains to be fully elucidated. Here, we exploit systemic lentiviral vector (LV) administration to achieve efficient and lifelong gene transfer to BECs in mice. We find that LV-marked BECs retain organoid formation potential and predominantly respond to liver damage; however, they are less clonogenic and display a hepatocyte-primed transcriptome compared to untransduced BECs. We thus identify a BEC subset committed to hepatocyte lineage in the absence of liver damage, characterized by a transcriptional network orchestrated by hepatocyte nuclear factor 4α. We also report in vivo targeting of such BECs in non-human primates. This work highlights intrinsic BEC heterogeneity and that in vivo LV gene transfer to the liver may persist following BEC-mediated repair of hepatic damage.

Indexed as

Bile DuctsEpithelial CellsGene Transfer TechniquesHepatocytesHomeostasisLentivirusLiverAnimalsGenetic VectorsLiver RegenerationMiceMice, Inbred C57BLOrganoidsCP: Stem cell researchin vivo gene therapylarge animal modelslentiviral vectorsliver damageliver organoidsliver stem cellstranslational research

Identifiers

PMID39998949
PMCPMC11936872

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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.