Kidney fibrosis presents a hallmark of chronic kidney disease. With ever-increasing patient numbers and limited treatment options available, novel strategies for therapeutic intervention in kidney disease are warranted. Fibrosis commonly results from a wound healing response to repeated or chronic tissue damage, irrespective of the underlying etiology, and can occur in virtually any solid organ or tissue. In order to identify targets relevant for kidney fibrosis, we aimed to employ CRISPR screening in primary human kidney fibroblasts. We demonstrate that CRISPR technology can be applied in primary kidney fibroblasts and can furthermore be used to conduct arrayed CRISPR screening using a high-content imaging readout in a whole genome-wide manner. Hits coming out of this screen were validated using orthogonal approaches and present starting points for validation of novel targets relevant to kidney disease.

中文翻译：

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在原发性器官成纤维细胞中进行全基因组阵列 CRISPR 筛选，以识别肾纤维化的调节因子。

肾纤维化是慢性肾病的标志。随着患者数量的不断增加和可用的治疗选择有限，有必要对肾脏疾病进行治疗干预的新策略。纤维化通常由对反复或慢性组织损伤的伤口愈合反应引起，与潜在的病因无关，并且几乎可以发生在任何实体器官或组织中。为了确定与肾纤维化相关的靶标，我们的目标是在原代人肾成纤维细胞中使用 CRISPR 筛选。我们证明 CRISPR 技术可应用于原代肾成纤维细胞，还可用于使用全基因组范围内的高内涵成像读数进行阵列 CRISPR 筛选。