Single-cell RNA-Seq of kidneys of Brg1-deficiency and wild type mice

We deleted the chromatin regulator Brg1 in Wnt4-expressing cells and FACS-purified Wnt4-lineage cells of wild-type and Brg1-deficient mouse kidneys. We then carried out single-cell RNA sequencing (scRNA-seq) to investigate the cell subpopulations and the effects of Brg1-deficiency in the differentiation of Wnt4-lineage cells. scRNA-seq analyses identify 35 clusters of Wnt4-descendant cells and uncover novel cell types and genes that have so far not been linked to Wnt4-lineage cells. Brg1-deficiency leads to increased endothelial, stromal, and smooth-muscle cells and decreased nephron tubular cells. In Brg1-deficient kidneys, the expression of Pttg1 and proliferation are increased in Wnt4-expressing precursors, which cannot transition to a characteristic tubular state and appear to undergo fibrosis. One Brg1-deficiency and one wild type samples本研究在表达Wnt4的细胞中敲除染色质调控因子Brg1，并通过荧光激活细胞分选术（FACS）纯化野生型及Brg1缺陷型小鼠肾脏中的Wnt4谱系细胞。随后我们开展了单细胞RNA测序（scRNA-seq），以探究Wnt4谱系细胞的细胞亚群特征，以及Brg1缺陷对其分化过程的影响。通过scRNA-seq分析，本研究共鉴定出35个Wnt4子代细胞簇，并发现了此前未被报道与Wnt4谱系细胞存在关联的新型细胞类型与基因。Brg1缺陷会导致内皮细胞、基质细胞和平滑肌细胞比例升高，而肾单位管状细胞比例降低。在Brg1缺陷型小鼠肾脏中，表达Wnt4的前体细胞内Pttg1的表达水平与细胞增殖能力均有所升高，这类细胞无法转化为典型的管状细胞状态，且似乎会发生纤维化。本研究包含1份Brg1缺陷型样本与1份野生型样本。