| First Author | Michalopulos MG | Year | 2026 |
| Journal | Development | Volume | 153 |
| Issue | 1 | PubMed ID | 41358813 |
| Mgi Jnum | J:377944 | Mgi Id | MGI:8279029 |
| Doi | 10.1242/dev.204964 | Citation | Michalopulos MG, et al. (2026) Defects in nephrogenesis result in an expansion of the Foxd1+ stromal progenitor population. Development 153(1):dev204964 |
| abstractText | The Foxd1+ stromal progenitor cells give rise to the majority of the renal interstitium; yet, much remains to be understood about how this self-renewing progenitor population is regulated during development. Here, we demonstrate that disruption of the nephron progenitor cell (NPC) lineage via loss of Wt1 (i.e. Six2cre;Wt1c/c) results in an expansion of Foxd1+ progenitor cells in mice. Analyses of two additional models (i.e. Wnt4-null mutants, which fail to form nephron structures similar to Six2cre;Wt1c/c kidneys, and NPC ablation via diphtheria toxin using the Six2cre;RosaDTAc/+) phenocopy the expansion in Foxd1+ cells and further confirm that mutant kidneys with defects in nephrogenesis develop an abnormal increase in the stromal progenitor population. Furthermore, single nuclei RNA-sequencing shows transcriptional changes in the Foxd1+ progenitor cells from Six2cre;Wt1c/c kidneys and identifies a distinct subcluster of the Foxd1+ stroma, which is maintained independent of signals from the nephrogenic niche in the Six2cre;RosaDTAc/+ model. Overall, these findings provide insights into the developmental regulation of the stromal progenitor population and uncover heterogeneity within the Foxd1+ cells, which undergo both cellular and molecular changes in response to defects in nephrogenesis. |
