Phua Yu Leng, Chen Kevin Hong, Hemker Shelby L, Marrone April K, Bodnar Andrew J, Liu Xiaoning, Clugston Andrew, Kostka Dennis, Butterworth Michael B, Ho Jacqueline
Rangos Research Center, UPMC Children's Hospital of Pittsburgh , Pittsburgh, Pennsylvania.
Division of Nephrology, Department of Pediatrics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
Am J Physiol Renal Physiol. 2019 May 1;316(5):F993-F1005. doi: 10.1152/ajprenal.00450.2018. Epub 2019 Mar 6.
We have previously demonstrated that loss of in nephron progenitors in a mouse model results in renal hypodysplasia and chronic kidney disease. Clinically, decreased congenital nephron endowment because of renal hypodysplasia is associated with an increased risk of hypertension and chronic kidney disease, and this is at least partly dependent on the self-renewal of nephron progenitors. Here, we present evidence for a novel molecular mechanism regulating the self-renewal of nephron progenitors and congenital nephron endowment by the highly conserved cluster. Whole transcriptome sequencing revealed that nephron progenitors lacking this cluster demonstrated increased expression. We showed that one member of the cluster, , is sufficient to repress expression in vitro and that perturbation of Cftr activity in nephron progenitors results in impaired proliferation. Together, these data suggest that regulates expression in nephron progenitors, with this interaction playing a role in appropriate nephron progenitor self-renewal during kidney development to generate normal nephron endowment.
我们之前已经证明，在小鼠模型中肾单位祖细胞中的[具体缺失内容]缺失会导致肾发育不全和慢性肾病。临床上，由于肾发育不全导致的先天性肾单位数量减少与高血压和慢性肾病风险增加相关，而这至少部分取决于肾单位祖细胞的自我更新。在此，我们提供证据表明，高度保守的[具体簇名称]簇通过一种新的分子机制调节肾单位祖细胞的自我更新和先天性肾单位数量。全转录组测序显示，缺乏该簇的肾单位祖细胞表现出[具体基因]表达增加。我们表明，该簇的一个成员[具体基因名称]足以在体外抑制[具体基因]表达，并且肾单位祖细胞中Cftr活性的扰动会导致增殖受损。总之，这些数据表明[具体基因]调节肾单位祖细胞中的[具体基因]表达，这种相互作用在肾脏发育过程中肾单位祖细胞的适当自我更新以产生正常肾单位数量中发挥作用。
