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Omics · study · 2026

A transient epithelial plasticity state defines the developmental window for uterine gland specification

Listed in NCBI GEO

Uterine gland development and function is essential for reproduction and women's health, yet the epithelial cell states and signaling interactions that govern gland fate specification are not well understood.

Description

Here, integration of single cell and spatial transcriptomics with organoid culture, lineage tracing, and genetic and hormonal perturbation models were used to define mechanisms regulating postnatal uterine epithelial differentiation.

A developmentally restricted epithelial plasticity state was identified that precedes luminal and glandular cell lineage segregation and accompanied by dynamic reorganization of stromal-epithelial communication during uterine differentiation. Pseudotime analysis revealed progressive acquisition of gland-associated programs, including forkhead box A2 (Foxa2), retinoic acid metabolic genes, and epithelial estrogen receptor alpha (Esr1) expression.

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Functional studies revealed that ESR1 acquisition and retinoic acid signaling suppress the multilayered organoid phenotype associated with epithelial plasticity, thereby promoting epithelial specification and lineage commitment. Moreover, neonatal hormonal perturbation of adenogenesis and conditional deletion of Foxa2 abolished this organoid phenotype. Together, these findings establish neonatal uterine organoids as a valuable system for investigating mechanisms that regulate glandular epithelial cell fate specification during reproductive tract development.

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Life Sciences
Inferred from text
Zoology 71%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE33117712 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[field].anzsrc:group:3109enrichment · NCBI GEOtaxonomy-embedding@1.1.0title+keywords+description (71%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title