Asymmetric inheritance of sister chromatids has long been predicted to be linked to discordant fates of daughter cells and even hypothesized to minimize accumulation of mutations in stem cells. Here, we use (2′S)-2′-deoxy-2′-fluoro-5-ethynyluridine (F-ara-EdU), bromodeoxyuridine (BrdU), and light sheet microscopy to track embryonic DNA in whole zebrafish. Larval development results in rapid depletion of older DNA template strands from stem cell niches in the retina, brain, and intestine. Prolonged label retention occurs in quiescent progenitors that resume replication in later development. High-resolution microscopy reveals no evidence of asymmetric template strand segregation in >100 daughter cell pairs, making it improbable that asymmetric DNA segregation prevents mutational burden according to the immortal strand hypothesis in developing zebrafish.

长期以来，人们一直预测姐妹染色单体的不对称遗传与子细胞的不一致命运有关，甚至假设可以最大限度地减少干细胞中突变的积累。在这里，我们使用 (2'S)-2'-deoxy-2'-fluoro-5-ethynyluridine (F - ara -EdU)、溴脱氧尿苷 (BrdU) 和光片显微镜来追踪整个斑马鱼的胚胎 DNA。幼虫发育导致视网膜、大脑和肠道干细胞壁龛中较老的 DNA 模板链迅速耗尽。长时间的标签保留发生在静止的祖细胞中，这些祖细胞在以后的发育中恢复复制。高分辨率显微镜显示在 > 100 个子细胞对中没有不对称模板链分离的证据，因此根据斑马鱼发育中的永生链假说，不对称 DNA 分离不可能防止突变负担。