Evidence map›Paper›PMID 41844162›Full record

ArticleCell systems2026

Single-cell epigenetic landscape, microenvironment interactions, and gene regulatory modules of non-functioning pituitary adenomas.

Zidong Zhang, Wan Sze Cheng, Keiko Taniguchi-Ponciano, Daniel Marrero-Rodríguez, Gregory R Smith, Hanna Pincas, Tyler J Sagendorf, Natalia Mendelev, Galia Strupinsky, Yongchao Ge and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell systems, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

22 authors.

Zidong ZhangDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Wan Sze ChengDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Keiko Taniguchi-PoncianoUnidad de Investigación Médica en Enfermedades Endocrinas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Daniel Marrero-RodríguezUnidad de Investigación Médica en Enfermedades Endocrinas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Gregory R SmithDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Hanna PincasDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Tyler J SagendorfBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
Natalia MendelevDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Galia StrupinskyDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Yongchao GeDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Michel ZamojskiDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Xi ChenLewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ 08540, USA.
Mary Anne S AmperDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Christopher Y ParkCenter for Computational Biology, Flatiron Institute, New York, NY 10010, USA.
Venugopalan D NairDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Cynthia L AndoniadouCentre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, UK; Department of Medicine III, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Judith L TurgeonDepartment of Internal Medicine, University of California, Davis, Davis, CA, USA.
Elena ZaslavskyDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Olga G TroyanskayaLewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ 08540, USA; Center for Computational Biology, Flatiron Institute, New York, NY 10010, USA; Department of Computer Science, Princeton University, Princeton, NJ 08540, USA.
Moises MercadoUnidad de Investigación Médica en Enfermedades Endocrinas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Stuart C SealfonDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: stuart.sealfon@mssm.edu.
Frederique Ruf-ZamojskiDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address: frederique.ruf-zamojski@csmc.edu.

Funding

MOLECULAR MECHANISM OF AGONISM AT THE GNRH RECEPTORR01DK046943 · NIDDK · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI STUART C. SEALFON · 1993 to 2026
$11.0M
Integrated systems biology of the pituitaryR56DK046943 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SEALFON, STUART C. · 2006 to 2024
$555k
NIDDK NIH HHS R01 DK046943NIDDK NIH HHS R56 DK046943
6 · The paper itself

Abstract

The epigenetic landscape and tumor microenvironment (TME) interactions of non-functioning pituitary adenomas (NFPAs), benign tumors with high morbidity and recurrence rates, are not well characterized. We completed single-nucleus (sn) multiomics assays on 4 gonadotrope NFPAs (34,819 cells) and 11 non-diseased postmortem control pituitaries (51,535 cells), finding decreased proportions of tumor-associated endothelial cells and pericytes and increased proportions of macrophages. We identified bidirectional tumor-macrophage crosstalk comprising nine ligand-receptor interactions and experimentally validated the macrophage-initiated SFRP1-FZD6 interaction, whose predicted target genes CCND1, CDK6, SGK1, and TGFBR2 were linked to tumorigenesis. We uncovered coordinated gene expression and chromatin accessibility programs, which distinguished adenoma cells from gonadotropes. Integrated transcriptome-chromatin modeling revealed gene regulatory circuits (GRCs) that showed altered activity in adenoma cells and were regulated by transcription factors (TFs), including PBX3 and MEF2C. Our study provides insight into the altered epigenetic gene control landscape and TME processes of the NFPA tumor phenotype. Our data are freely available at https://rstudio-connect.hpc.mssm.edu/nfpa_browser/.

Indexed as

AdenomaPituitary NeoplasmsEpigenesis, GeneticGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansMultiomicsSingle-Cell AnalysisSingle-Cell Gene Expression AnalysisTranscriptomeTumor Microenvironmentadenoma classificationchromatin accessibilitycopy number variationgene regulatory circuitmultiomicspituitary adenomassingle-cell analysistranscriptometumor microenvironment

Identifiers

PMID41844162
PMCPMC13430750

What OpenQuestion holds

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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 OpenQuestion graph.