Hilliard Sylvia, Song Renfang, Liu Hongbing, Chen Chao-Hui, Li Yuwen, Baddoo Melody, Flemington Erik, Wanek Alanna, Kolls Jay, Saifudeen Zubaida, El-Dahr Samir S
Department of Pediatrics, Section of Pediatric Nephrology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Department of Pathology & Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Biol Open. 2019 May 20;8(5):bio042754. doi: 10.1242/bio.042754.
Six2 cap mesenchyme cells, also called nephron progenitor cells (NPC), are precursors of all epithelial cell types of the nephron, the filtering unit of the kidney. Current evidence indicates that perinatal 'old' NPC have a greater tendency to exit the progenitor niche and differentiate into nascent nephrons than their embryonic 'young' counterpart. Understanding the underpinnings of NPC development may offer insights to rejuvenate old NPC and expand the progenitor pool. Here, we compared the chromatin landscape of young and old NPC and found common features reflecting their shared lineage but also intrinsic differences in chromatin accessibility and enhancer landscape supporting the view that old NPC are epigenetically poised for differentiation. Annotation of open chromatin regions and active enhancers uncovered the transcription factor Bach2 as a potential link between the pro-renewal MAPK/AP1 and pro-differentiation Six2/b-catenin pathways that might be of critical importance in regulation of NPC fate. Our data provide the first glimpse of the dynamic chromatin landscape of NPC and serve as a platform for future studies of the impact of genetic or environmental perturbations on the epigenome of NPC.
Six2帽间充质细胞，也称为肾单位祖细胞（NPC），是肾脏过滤单位肾单位所有上皮细胞类型的前体。目前的证据表明，围产期的“老”NPC比胚胎期的“年轻”NPC更倾向于离开祖细胞龛并分化为新生肾单位。了解NPC发育的基础可能为使老NPC恢复活力和扩大祖细胞库提供见解。在这里，我们比较了年轻和老NPC的染色质景观，发现了反映它们共同谱系的共同特征，但也发现了染色质可及性和增强子景观的内在差异，支持老NPC在表观遗传上准备好分化的观点。对开放染色质区域和活性增强子的注释揭示了转录因子Bach2是促更新的MAPK/AP1和促分化的Six2/β-连环蛋白途径之间的潜在联系，这可能在NPC命运调控中至关重要。我们的数据首次展示了NPC动态染色质景观，并为未来研究遗传或环境扰动对NPC表观基因组的影响提供了一个平台。
