Renal Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
JCI Insight. 2017 Jan 26;2(2):e88848. doi: 10.1172/jci.insight.88848.
The neonatal mouse kidney retains nephron progenitor cells in a nephrogenic zone for 3 days after birth. We evaluated whether de novo nephrogenesis can be induced postnatally beyond 3 days. Given the long-term implications of nephron number for kidney health, it would be useful to enhance nephrogenesis in the neonate. We induced nephron reduction by cryoinjury with or without contralateral nephrectomy during the neonatal period or after 1 week of age. There was no detectable compensatory de novo nephrogenesis, as determined by glomerular counting and lineage tracing. Contralateral nephrectomy resulted in additional adaptive healing, with little or no fibrosis, but did not also stimulate de novo nephrogenesis. In contrast, injury initiated at 1 week of age led to healing with fibrosis. Thus, despite the presence of progenitor cells and ongoing nephron maturation in the newborn mouse kidney, de novo nephrogenesis is not inducible by acute nephron reduction. This indicates that additional nephron progenitors cannot be recruited after birth despite partial renal ablation providing a reparative stimulus and suggests that nephron number in the mouse is predetermined at birth.
新生小鼠肾脏在出生后 3 天内保留肾祖细胞在肾发生区。我们评估了出生后 3 天以上是否可以诱导新的肾发生。由于肾单位数量对肾脏健康的长期影响，增强新生儿的肾发生将是有用的。我们通过在新生儿期或 1 周龄后进行冷冻损伤诱导肾单位减少，同时或不进行对侧肾切除术。通过肾小球计数和谱系追踪确定，没有检测到可检测的新的肾发生代偿性。对侧肾切除术导致适应性愈合，纤维化程度较低或没有，但也没有刺激新的肾发生。相比之下，在 1 周龄时开始的损伤导致纤维化愈合。因此，尽管新生小鼠肾脏中存在祖细胞和持续的肾单位成熟，但急性肾单位减少不能诱导新的肾发生。这表明，尽管部分肾切除提供修复刺激，但出生后不能招募额外的肾祖细胞，这表明小鼠的肾单位数量在出生时就已预先确定。
