The embryonic renal stroma consists of multiple molecularly distinct cell subpopulations, the functional significance of which is largely unknown. Previous work has demonstrated that the transcription factors YAP and TAZ play roles in the development and morphogenesis of the nephrons, collecting ducts, and nephron progenitor cells.

In embryonic mouse kidneys, we identified a subpopulation of stromal cells with enriched activity in YAP and TAZ. To evaluate the function of these cell types, we genetically ablated both Yap and Taz from the stromal progenitor population and examined how gene activity and development of YAP/TAZ mutant kidneys are affected over a developmental time course.

We found that YAP and TAZ are active in a subset of renal interstitium and that stromal-specific coablation of YAP/TAZ disrupts cortical fibroblast, pericyte, and myofibroblast development, with secondary effects on peritubular capillary differentiation. We also demonstrated that the transcription factor SRF cooperates with YAP/TAZ to drive expression of at least a subset of renal myofibroblast target genes and to specify myofibroblasts but not cortical fibroblasts or pericytes.

These findings reveal a critical role for YAP/TAZ in specific embryonic stromal cells and suggest that interaction with cofactors, such as SRF, influence the expression of cell type–specific target genes, thus driving stromal heterogeneity. Further, this work reveals functional roles for renal stroma heterogeneity in creating unique microenvironments that influence the differentiation and maintenance of the renal parenchyma.

胚胎肾基质由多个分子上不同的细胞亚群组成，其功能意义很大程度上未知。先前的工作已证明转录因子 YAP 和 TAZ 在肾单位、集合管和肾单位祖细胞的发育和形态发生中发挥作用。

在胚胎小鼠肾脏中，我们鉴定出了 YAP 和 TAZ 活性丰富的基质细胞亚群。为了评估这些细胞类型的功能，我们从基质祖细胞群中基因消除了Yap和Taz ，并检查了 YAP/TAZ 突变肾的基因活性和发育在发育时间过程中如何受到影响。

我们发现 YAP 和 TAZ 在肾间质的子集中具有活性，并且 YAP/TAZ 的基质特异性共消融会破坏皮质成纤维细胞、周细胞和肌成纤维细胞的发育，并对肾小管周围毛细血管分化产生二次影响。我们还证明转录因子 SRF 与 YAP/TAZ 配合驱动至少一部分肾肌成纤维细胞靶基因的表达，并指定肌成纤维细胞但不指定皮质成纤维细胞或周细胞。

这些发现揭示了 YAP/TAZ 在特定胚胎基质细胞中的关键作用，并表明与 SRF 等辅助因子的相互作用影响细胞类型特异性靶基因的表达，从而驱动基质异质性。此外，这项工作揭示了肾基质异质性在创造影响肾实质分化和维持的独特微环境中的功能作用。