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Omics · study · 2026

The Transcription Factor TCF21 is Necessary for Adoption of Cell Fates by Foxd1+ Stromal Progenitors during Kidney Development

Listed in NCBI GEO

The stromal compartment of the developing kidney arises from Foxd1-expressing progenitors and gives rise to diverse cell types essential for nephrogenesis, including the renal stroma, capsule, mesangial cells, renin cells, pericytes, and vascular smooth muscle cells (VSMCs).

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However, the molecular mechanisms guiding their fate specification remain incompletely defined. Here, we identify the basic helix-loop-helix transcription factor Tcf21 as a critical determinant of stromal cell identity during kidney development.

We performed single-cell RNA sequencing (scRNA-seq) on Foxd1-lineage cells isolated from embryonic day 14.5 (E14.5) Tcf21 conditional knockout (Tcf21-cKO) Foxd1Cre/+;Rosa26mTmG;Tcf21f/f and control kidneys, revealing seven transcriptionally distinct stromal subpopulations. Loss of Tcf21 resulted in marked depletion of Medullary/Perivascular stroma, Collecting duct associated stroma, Proliferating stroma, and Nephrogenic zone associated subpopulations, confirmed by immunostaining, which revealed severe constriction of medullary and collecting duct stromal spaces.

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Additionally, we identified a novel cluster unique to Tcf21-cKO kidneys, characterized by high expression of Endomucin (Emcn). These cells spanned pseudotime trajectories and were distributed broadly across the mutant kidney. These findings were corroborated by E14.5 single-cell ATAC sequencing (scATAC-seq), which confirmed altered chromatin accessibility in Tcf21-deficient stroma.

To assess the persistence and downstream impact of these defects, we performed bulk and scRNA-seq at E18.5, revealing sustained expansion of Emcn+ cells with pro-fibrotic and perivascular transcriptional programs. Histological analyses at 2 months demonstrated lasting architectural disruption, interstitial fibrosis, and impaired renal function in Tcf21-cKO mice. Our results identify Tcf21 as a key regulator of stromal progenitor fate and establish a developmental origin for fibrotic remodeling and kidney dysfunction.

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Expression profiling by high throughput sequencing · Genome binding/occupancy profiling by high throughput sequencing · Mus musculus
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Life Sciences
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RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 11 field assertions
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NCBI GEOGSE32595514 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
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[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:single-cell-rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
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