Evidence map›Paper›PMID 41990579›Full record

ArticleJHEP reports : innovation in hepatology2026

Single-cell transcriptomics reveals the impact of sex and age in the healthy human liver.

Raza Ur Rahman, Eliana T Epstein, Shane Murphy, Liat Amir-Zilberstein, Cristin McCabe, Toni M Delorey, Hope Koene, Lilly Fernandes, Kenneth K Tanabe, Motaz Qadan and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JHEP reports : innovation in hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. An Integrated Multi-omics Single Cell Atlas of the Human RPE and Choroid.bioRxiv : the preprint server for biology · 2026
    Article
  4. Review
  5. 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

15 authors.

Raza Ur RahmanDivision of Gastroenterology, University of Massachusetts Chan Medical School, Worcester, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Eliana T EpsteinDivision of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.
Shane MurphyBroad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Liat Amir-ZilbersteinBroad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cristin McCabeBroad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Toni M DeloreyBroad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Hope KoeneDivision of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.
Lilly FernandesDivision of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.
Kenneth K TanabeDivision of Gastrointestinal and Oncologic Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
Motaz QadanDivision of Gastrointestinal and Oncologic Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
Cristina R FerroneDivision of Gastrointestinal and Oncologic Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
David L BergerDivision of Gastrointestinal and Oncologic Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
Angela ShihDivision of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Jacques DeguineBroad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Alan C MullenDivision of Gastroenterology, University of Massachusetts Chan Medical School, Worcester, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: alan.mullen@umassmed.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsThe liver is a vital organ composed of parenchymal, non-parenchymal, and immune cell populations. Single-cell sequencing approaches now provide the opportunity to understand how sex and age influence gene expression and cellular function across cell types within the liver.

methodsWe analyzed the cellular composition and intercellular interactions of the human liver through single-nucleus RNA sequencing, incorporating insights from 37 healthy liver samples. The dataset contains cells from female and male donors spanning more than seven decades of life, and analysis was performed to evaluate the impact of sex and age on differential gene expression, pathway enrichment, and predicted ligand-receptor and protein-protein interactions.

resultsExcluding the X and Y chromosomes, we identified 374 genes uniquely enriched in cells of the female liver and 520 genes enriched in cells of the male liver. Differential expression analysis defined unique circuitries enriched within each cell type between females and males and their impact on cell-cell communication and response to external signals, including enrichment of cholesterol metabolism (p <1.64 x 10

conclusionsThese results define the activities of healthy cell types within the liver across sex and age, providing a foundation for studies to examine how ancestry, geography, and disease states influence liver function within these contexts. IMPACT AND IMPLICATIONS: Our study provides a comprehensive single-cell analysis of 37 healthy human liver samples, revealing how sex and age influence gene expression profiles, cellular interactions, and signaling responses across liver cell types and subtypes. These insights are of particular significance for researchers investigating the influence of sex and age on cellular responses to injury and treatment of injury. Furthermore, this dataset serves as a healthy reference, enabling future studies to understand how ancestry, geography, and disease states shape liver biology in the context of age and sex.

Indexed as

Age-associated changesAgingCellular senescenceHealthy reference atlasHuman liver: cell–cell communicationInsulin growth factor (IGF)Neuregulin (NRG)Pathway enrichment analysisProtein–protein interaction networksSex differencesSexual dimorphism

Identifiers

PMID41990579
PMCPMC13101288

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.