Molecular dissection of the balance between SIX2, BMPs, TGFB and WNT-dependent regulation of self-renewal in UdRPCs
Mammalian kidney organogenesis involves reciprocal epithelial-mesenchymal interactions that drive iterative cycles of nephron formation. Development of the metanephric kidney depends on tightly regulated interplay between self-renewal and differentiation of a nephron progenitor cell (NPC) pool.
Studies in the mouse have demonstrated that the transcription factor Six2 acts cell autonomously to maintain nephron progenitor cells. Furthermore, Osr1 plays crucial roles in Six2-dependent maintenance of nephron progenitors during mammalian nephrogenesis by antagonizing Wnt-directed nephrogenic differentiation. WT1 maintains nephron progenitor cells by modulating FGF signals which is required for maintaining self-renewal in UdRPCs
In our earlier studies we showed that FGF, WNT and TGFβ signaling pathways modulate self-renewal in human urine-derived renal progenitors.
https://pubmed.ncbi.nlm.nih.gov/31959818/
Additionally, we identify downstream targets of these key transcription factors (SIX2, WT1 and JNK) after RNAi-based transient knockdowns coupled with RNA-Seq and Chip-Seq followed by detailed bioinformatics analyses to identify direct downstream targets, regulated genes, pathways and gene ontologies ultimately leading to a human network model for SIX2 and WT1- dependent regulation of self-renewal.