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Record W4414524823 · doi:10.1101/2025.09.23.677404

A Rare Multipotent Peg-like Epithelial Cell is a Candidate Cell-of-Origin for High-Grade Serous Ovarian Cancer

2025· preprint· en· W4414524823 on OpenAlexaff
Megan L. Ritting, Wenmei Yang, Syed Mohammed Musheer Aalam, Hui Zhao, Feng Liang, Jianning Song, Mihai Dumbravă, Wazim Mohammed Ismail, Dong‐Gi Mun, Chunling Hu, Keyur Chaludiya, Geng Xian Shi, Daphne Norma Crasta, Kenneth Schaufelberger, Jeffrey R. Janus, Guruprasad Kalthur, S. John Weroha, Scott H. Kaufmann, Anguraj Sadanandam, David J. H. F. Knapp, Chen Wang, Akhilesh Pandey, Alexandre Gaspar‐Maia, Fergus J. Couch, Mark E. Sherman, Jamie N. Bakkum‐Gamez, Nagarajan Kannan

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Research and Treatments
Canadian institutionsUniversité de Montréal
Fundersnot available
KeywordsFallopian tubeOrganoidSerous fluidEpitheliumOvarian cancerWnt signaling pathwayEpithelial–mesenchymal transitionMesonephric ductEpithelial ovarian cancer

Abstract

fetched live from OpenAlex

Abstract To illuminate the origins of high-grade serous ovarian cancer (HGSOC), the most lethal and common form of ovarian cancer, we have created a comprehensive living organoid biobank of human fallopian tube tissue, which is thought to be the origin of this cancer. Through optimized culture protocols and integrated multi-omic profiling—including single-cell RNA sequencing, chromatin accessibility (ATAC) analysis, proteomics, and secretomics—we assembled the largest molecular atlas of the fallopian tube epithelium to date. This resource revealed diverse epithelial lineages and regulatory networks, including a rare, multipotent epithelial subpopulation with hybrid epithelial–mesenchymal features. Spatially localized to the basal epithelium and resembling mesonephric developmental precursors, these cells exhibit transcriptomic and proteomic similarities to the mesenchyme-like subtype of HGSOC, implicating them as potential cells-of-origin. Their molecular identity is preserved in organoid models, enabling future mechanistic and translational studies. This resource, which advances fundamental understanding of epithelial hierarchy and cancer susceptibility, provides a platform to inform early detection and prevention strategies for aggressive forms of ovarian cancer. Highlights Establishment of a clinically annotated fallopian tube organoid biobank enables delineation of epithelial lineage hierarchies and differentiation capacity. Multi-omics integration defines robust, lineage-specific transcriptional and regulatory networks in the fallopian tube epithelium. A rare basal epithelial subpopulation with mesenchymal features aligns with a mesenchyme-like subtype of high-grade serous ovarian cancer. Rare basal ‘peg’ cells exhibit fetal mesonephric developmental transcriptional programs and are maintained ex-vivo in fallopian tube organoids.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.261
Teacher spread0.248 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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