Kidney Week

Abstract: TH-PO388

Transcription Factor Tcf21 Is Required for Specifying Foxd1 Cells to the Juxtaglomerular Cell Lineage

Session Information

• Development, Organoids, Injury, and Regeneration
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Development, Stem Cells, and Regenerative Medicine

• 600 Development, Stem Cells, and Regenerative Medicine

Authors

• Finer, Gal, Division of Pediatric Nephrology, Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois, United States

Gal Finer, MD, PhD

• Anjum, Hina, Division of Pediatric Nephrology, Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois, United States

Hina Anjum, PhD

• Yacu, George S., Division of Pediatric Nephrology, Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois, United States

George S. Yacu

• Medrano, Silvia, Department of Pediatrics, Child Health Research Center, University of Virginia, Charlottesville, Virginia, United States

Silvia Medrano, PhD

• Gomez, Roberto Ariel, Department of Pediatrics, Child Health Research Center, University of Virginia, Charlottesville, Virginia, United States

Roberto Ariel Gomez, MD

• Sequeira Lopez, Maria Luisa S., Department of Pediatrics, Child Health Research Center, University of Virginia, Charlottesville, Virginia, United States

Maria Luisa S. Sequeira Lopez, MD

• Quaggin, Susan E., Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Susan E. Quaggin, MD, FASN

Background

Renin is crucial for blood pressure regulation and electrolyte balance. Renin expressing cells are known to arise from the Foxd1+ stromal progenitors; however, the factors guiding Foxd1+ cells towards the renin-secreting cell fate remain poorly understood. Tcf21 is a bHLH transcription factor of the metanephric mesenchyme that plays a crucial role in kidney development. We have previously shown that deletion of Tcf21 in Foxd1+ cells (Foxd1^Cre/+;Tcf21^f/f) results in paucity of vascular mural cells and in disorganized renal arterial tree. Here, we sought to examine the relationship between Tcf21 and renin cells during kidney development and test whether Tcf21 is implicated in juxtaglomerular cell differentiation.

Methods

We performed histological examination of kidney samples from two mouse models and littermate controls: one with conditional inactivation of Tcf21 in Foxd1+ expressing cells (Foxd1^Cre/+ Tcf21^f/f) and the other with inactivation of Tcf21 in renin-expressing cells (Ren1d^Cre/+ Tcf21^f/f).

Results

Immunostaining for renin demonstrated that kidneys of Foxd1^Cre/+;Tcf21^f/f have fewer renin-positive spots at E16.5 and E18.5 compared with controls. In-situ hybridization for renin mRNA showed reduced expression in Foxd1^Cre/+;Tcf21^f/f kidneys at E14.5, E16.5, and E18.5. Together, these data suggest that stromal expression of Tcf21 is required for the emergence of renin cells. To dissect the role of Tcf21 in juxtaglomerular (JG) cells, we deleted Tcf21 upon renin promoter activation (Ren1^dCre/+;Tcf21^f/f). Interestingly, the Ren1^dCre/+;Tcf21^f/f kidney showed normal arterial tree at E16.5 identical to controls. Furthermore, inactivation of Tcf21 upon renin expression did not alter kidney morphology in two- and four-month-old mice. Finally, expression renin mRNA was similar between Ren1^dCre/+;Tcf21^f/f and controls at 2 months.

Conclusion

Taken together, our findings suggest that Tcf21 expression in Foxd1+ cells is essential for specifying the fate of these cells into juxtaglomerular cells. However, once renin cell identity is assumed, Tcf21 is dispensable.

Funding

• NIDDK Support