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Abstract: FR-OR043

Differentiation of Stromal Cells to Renin Cells During Embryonic Vascular Development

Session Information

  • Development and Stem Cells
    November 08, 2019 | Location: 152, Walter E. Washington Convention Center
    Abstract Time: 04:54 PM - 05:06 PM

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine

Authors

  • Nagalakshmi, Vidya K., University of Virginia, Charlottesville, Virginia, United States
  • Sequeira Lopez, Maria Luisa S., University of Virginia, Charlottesville, Virginia, United States
  • Gomez, Roberto Ariel, University of Virginia, Charlottesville, Virginia, United States
Background


Kidney arterioles are formed by the assembly of different cell types such as smooth muscle cells, endothelial cells and renin cells. Foxd1 positive stromal cells are precursors of all mural cells of the renal vasculature including the renin producing cells. How the Foxd1 cells convert to renin cells is not known. Therefore, we aimed to understand the cell fate changes during differentiation of renin producing cells from their Foxd1+ stromal cell precursors throughout kidney development using single cell genomic approaches. In the current study we analyzed the transcriptome profile of GFP+ cells FACS sorted from the kidneys of E15.5-Foxd1Cre.mTmG mice embryos.

Methods

Single cell capture was performed using the Fluidigm C1 platform and subsequent RNA sequencing was done using Illumina HiSeq4000.

Results

Sequencing analyses with Fluidigm-Singular software revealed that within the Foxd1 lineage cells, cells specific for various mural cell lineage markers clustered separately, indicating the unique molecular repertoire acquired by them during their differentiation from a common precursor population. Approximately 7.5% of the Foxd1 lineage single cells captured from E15.5 kidneys were renin positive. Unsupervised hierarchical clustering was able to identify renin positive cells as a distinct cell cluster separated from the rest of the group. Pathway analyses using the PANTHER classification system for differentially expressed genes between renin positive and negative cells detected pathways critical for vascular morphogenesis such as Angiogenesis (Dlk1, F2r, Rhob, Crk), Wnt signaling (Smarcb1), and Notch signaling (Dlk1) only in renin positive cells. Smarcb1 regulates actin cytoskeleton network and loss of Smarcb1 enhances the migratory potential of the cells. Earlier studies in our lab showed that disruption of Notch pathway in renin cells and Foxd1 precursor cells results in deregulation of genes associated with vascular smooth muscle cells and defective vascular morphogenesis. The non-canonical Notch ligand Delta-like 1 (Dlk1) exhibits an inhibitory role in the regulation of angiogenesis and its precise role in renin producing cells needs to be investigated further.

Conclusion

Our results suggests that Notch and Wnt pathways govern the differentiation of stromal cells to renin cells as they assemble to form the kidney vasculature.

Funding

  • NIDDK Support