Growth and regeneration of adult β cells does not involve specialized progenitors
Growth and regeneration of adult β cells does not involve specialized progenitors
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DOI：
10.1016/j.devcel.2007.04.011
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发表时间：
2007-05-01
影响因子：
11.8
通讯作者：
Kushner, Jake A.
中科院分区：
文献类型：
--
作者：
Teta, Monica;Rankin, Matthew M.;Kushner, Jake A.
在许多成体组织中，细胞祖细胞的特征仍然很差，部分原因是缺乏鉴定祖细胞及其后代的公正技术。为了解决这个基本问题，我们开发了一种新的基于 DNA 类似物的谱系追踪技术来检测体内多轮细胞分裂。在这里，我们应用这种技术来确定胰岛分泌胰岛素的β细胞的成体谱系机制，这是糖尿病研究中尚未解决的一个重要问题。正如预期的那样，胃肠道和皮肤上皮涉及专门的祖细胞，这些祖细胞反复分裂以产生有丝分裂后细胞。相比之下，特殊的祖细胞对成年β细胞没有贡献，即使在急性β细胞再生过程中也是如此。相反，β细胞是均匀自我更新的产物，复制不应期会减慢复制不应期，从而阻止β细胞立即重新分裂。我们的方法为以前无法进入的发育生态位提供了公正的解决方案，并且可以在没有候选标记的情况下阐明谱系机制。
Cellular progenitors remain poorly characterized in many adult tissues, limited in part by the lack of unbiased techniques to identify progenitors and their progeny. To address this fundamental problem, we developed a novel DNA analog-based lineage-tracing technique to detect multiple rounds of cell division in vivo. Here, we apply this technique to determine the adult lineage mechanism of the insulin-secreting beta cells of pancreatic islets, an important unresolved question in diabetes research. As expected, gastrointestinal and skin epithelia involve specialized progenitors that repeatedly divide to give rise to postmitotic cells. In contrast, specialized progenitors do not contribute to adult beta cells, not even during acute beta cell regeneration. Instead, beta cells are the products of uniform self-renewal, slowed by a replication refractory period that prevents beta cells from immediately redividing. Our approach provides unbiased resolution of previously inaccessible developmental niches and can elucidate lineage mechanisms without candidate markers.