Evidence map›Paper›PMID 40831751›Full record

ArticleFrontiers in cell and developmental biology2025

Spatial transcriptomics reveals Inhba/Smad2/E2f4 axis in Lrp2

Man Luo, Xiaona Tian, Li Li, Guomei Zhang, Wenzhi Liu, Linlin Mei, Haoran Li, Xiaoyan You, Dongmei Zhang, Mengsi Zhou and 3 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in cell and developmental biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Man Luo *Department of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Xiaona Tian *Department of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Li LiDepartment of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Guomei ZhangDepartment of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Wenzhi LiuDepartment of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Linlin MeiDepartment of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Haoran LiDepartment of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Xiaoyan YouDepartment of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Dongmei ZhangDepartment of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Mengsi ZhouDepartment of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Cheng XiaoInstitute of Muscle Biology and Growth, Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
Jianping YeInstitute of Trauma and Metabolism, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Xiaofeng YangDepartment of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by elevated androgen levels and impaired follicular development. A hallmark of PCOS is the excessive proliferation of thecal cells (TCs), which are critical for androgen production. However, the molecular mechanisms underlying this aberrant cellular expansion remain incompletely understood. Methods: A DHEA-induced mouse model was used to recapitulate the hormonal and ovarian features of human PCOS. Spatial transcriptomics was employed to profile gene expression in ovarian tissue at cellular resolution. Differential expression analysis, pathway enrichment, and spatial co-localization were performed to identify regulatory networks. Functional assays were conducted in cultured TCs using siRNA-mediated knockdown of target genes, and cell proliferation and cell cycle progression were evaluated using EdU incorporation and flow cytometry. Results: Spatial transcriptomic profiling revealed widespread transcriptional changes in the ovaries of PCOS mice, including a marked expansion of a TCs subpopulation with high Lrp2 expression. This subset exhibited enhanced activity in genes involved in androgen synthesis and cell cycle regulation. A signaling axis comprising Inhba, Smad2, and E2f4 was identified as a key regulator of this proliferative response, with all three genes co-expressed in the affected regions. Knockdown of any component of this axis significantly suppressed TCs proliferation Conclusion: The Inhba/Smad2/E2f4 axis contributes to thecal cell hyperplasia and androgen excess in PCOS, and may serve as a mechanistic entry point for further investigation into the regulation of TCs proliferation in this disorder.

Indexed as

androgenpolycystic ovary syndromeproliferationspatial transcriptomicthecal cell

Identifiers

PMID40831751
PMCPMC12358492

What Socratic holds

Textmetadata
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.