ABSTRACT

The mammalian kidney has extensive repair capacity; however, identifying adult renal stem cells has proven elusive. We applied an epigenetic marker of foetal cell origin (FCO) in diverse human tissues as a probe for developmental cell persistence, finding a 5.4-fold greater FCO proportion in kidney. Normal kidney FCO proportions averaged 49% with extensive interindividual variation. FCO proportions were significantly negatively correlated with immune-related gene expression and positively correlated with genes expressed in the renal medulla, including those involved in renal organogenesis (e.g., FGF2, PAX8, and HOXB7). FCO associated genes also mapped to medullary nephron segments in mouse and rat, suggesting evolutionary conservation of this cellular compartment. Renal cancer patients whose tumours contained non-zero FCO scores survived longer. The kidney appears unique in possessing substantial foetal epigenetic features. Further study of FCO-related gene methylation may elucidate regenerative regulatory programmes in tissues without apparent discrete stem cell compartments.

摘要

哺乳动物的肾脏具有广泛的修复能力；然而，鉴定成体肾干细胞已被证明是难以捉摸的。我们在不同的人体组织中应用胎儿细胞起源 (FCO) 的表观遗传标记作为发育细胞持久性的探针，发现肾脏中的 FCO 比例高出 5.4 倍。正常肾脏 FCO 比例平均为 49%，个体间差异很大。FCO 比例与免疫相关基因表达呈显着负相关，与肾髓质中表达的基因呈正相关，包括参与肾器官发生的基因（例如，FGF2、PAX8 和 HOXB7）. FCO 相关基因也映射到小鼠和大鼠的髓质肾单位片段，表明这种细胞区室的进化保守性。肿瘤包含非零 FCO 评分的肾癌患者存活时间更长。肾脏似乎具有独特的胎儿表观遗传特征。对 FCO 相关基因甲基化的进一步研究可能会阐明没有明显离散干细胞区室的组织中的再生调节程序。