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Peer-reviewedCC BY 4.0Development (Cambridge, England)

Multi-gene biomarkers reveal spatial organization and subpopulation-specific damage response in biliary epithelial cells

  • Kendall G. Kanakanui1,2
  • Fransky Hantelys3
  • Hannah R. Hrncir3,4
  • Sergei Bombin3
  • Adam D. Gracz2
4 affiliations
  1. 1Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta, GA 30322, USA
  2. 2Department of Cell Biology & Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
  3. 3Department of Medicine, Division of Digestive Diseases, Emory University, Atlanta, GA 30322, USA
  4. 4Graduate Program in Biochemistry, Cell and Developmental Biology, Emory University, Atlanta, GA 30322, USA
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Abstract

Biliary epithelial cell (BEC) heterogeneity remains challenging to define. Here, we performed scRNA-seq on Sox9EGFP+ liver epithelium from mice subjected to bile duct ligation (BDL) and sham controls. We identified 4 BEC subpopulations in sham controls, each associated with specific enrichment of a minimal one or two gene biomarker (‘metagene’). Metagenes were validated by hybridization chain reaction fluorescence in situ hybridization, which also facilitated spatial analysis of intrahepatic bile ducts. BECs belonging to a given subpopulation were most likely to have neighbors of the same identity, forming homogenous cellular compartments within otherwise heterogeneous ducts. Subpopulation specific differential gene expression (DGE) analysis revealed that BDL decreases transcriptomic heterogeneity among BECs by suppressing subpopulation specific genes. BDL samples also included a proliferative subpopulation not found in controls, which contained populations enriched for three of the four metagenes. All BEC subpopulations were observed in vitro in monolayer cultures, where they clustered spatially with BECs of the same subtype. Together, our data demonstrate that metagene biomarkers facilitate spatial localization of BEC subpopulations in situ, identify subpopulation-specific injury responses and confirm that BEC heterogeneity is preserved in vitro.

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Cite

BibTeXRIS
BibTeX
@article{kanakanui2026multigene,
  title = {{Multi-gene biomarkers reveal spatial organization and subpopulation-specific damage response in biliary epithelial cells}},
  author = {Kendall G. Kanakanui and Fransky Hantelys and Hannah R. Hrncir and Sergei Bombin and Adam D. Gracz},
  journal = {Development (Cambridge, England)},
  year = {2026},
  month = oct,
  doi = {10.1242/dev.205690},
  url = {https://doi.org/10.1242/dev.205690},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Multi-gene biomarkers reveal spatial organization and subpopulation-specific damage response in biliary epithelial cells
AU  - Kendall G. Kanakanui
AU  - Fransky Hantelys
AU  - Hannah R. Hrncir
AU  - Sergei Bombin
AU  - Adam D. Gracz
PY  - 2026
DA  - 2026/10/12
JO  - Development (Cambridge, England)
DO  - 10.1242/dev.205690
UR  - https://doi.org/10.1242/dev.205690
AB  - Biliary epithelial cell (BEC) heterogeneity remains challenging to define. Here, we performed scRNA-seq on Sox9EGFP+ liver epithelium from mice subjected to bile duct ligation (BDL) and sham controls. We identified 4 BEC subpopulations in sham controls, each associated with specific enrichment of a minimal one or two gene biomarker (‘metagene’). Metagenes were validated by hybridization chain reaction fluorescence in situ hybridization, which also facilitated spatial analysis of intrahepatic bile ducts. BECs belonging to a given subpopulation were most likely to have neighbors of the same identity, forming homogenous cellular compartments within otherwise heterogeneous ducts. Subpopulation specific differential gene expression (DGE) analysis revealed that BDL decreases transcriptomic heterogeneity among BECs by suppressing subpopulation specific genes. BDL samples also included a proliferative subpopulation not found in controls, which contained populations enriched for three of the four metagenes. All BEC subpopulations were observed in vitro in monolayer cultures, where they clustered spatially with BECs of the same subtype. Together, our data demonstrate that metagene biomarkers facilitate spatial localization of BEC subpopulations in situ, identify subpopulation-specific injury responses and confirm that BEC heterogeneity is preserved in vitro.
SN  - 0950-1991
SN  - 1477-9129
ER  -