All beta cells contribute equally to islet growth and maintenance.
All beta cells contribute equally to islet growth and maintenance.
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DOI：
10.1371/journal.pbio.0050163
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发表时间：
2007-07
期刊：
影响因子：
9.8
通讯作者：
Melton D
中科院分区：
文献类型：
--
作者：
Brennand K;Huangfu D;Melton D
在健康的成年小鼠中，β细胞群不是由干细胞维持，而是由分化的β细胞的复制维持。然而，尚不清楚是否所有 β 细胞对生长和维持的贡献均等，因为可能有些细胞可以复制，而另一些细胞则不能。准确了解哪些细胞负责β细胞复制将为体外扩增β细胞的尝试提供信息，β细胞是治疗糖尿病的细胞替代疗法的潜在来源。为了解决这个问题进行了两个实验。首先，随着时间的推移，跟踪组蛋白 2B 绿色荧光蛋白 (H2BGFP) 表达脉冲产生的荧光水平，以确定该标记物如何随着细胞分裂而稀释；观察到整个 β 细胞群中标签的均匀丢失。其次，完成分裂期β细胞的克隆分析；所有克隆的大小相当。这些结果支持β细胞库在复制能力方面是同质的结论，并表明所有β细胞都是体外扩增的候选者。鉴于在肝细胞群中的类似观察，我们推测对于缺乏成体干细胞的组织，它们通过所有分化细胞的复制得到同等的补充。胰腺的 β 细胞负责产生胰岛素，其破坏会导致 I 型糖尿病。 β细胞的维持、生长和再生修复被认为主要（如果不是完全）通过现有β细胞的复制而不是通过成体干细胞进行。然而，之前尚不清楚是否所有 β 细胞都以相同的速率分裂，或者是否存在多个 β 细胞亚群，其中一些具有高度复制性，而另一些则非常缓慢地分裂，可能是有丝分裂后的。我们进行了两种类型的实验来确定是否所有 β 细胞都相似：标记保留分析和克隆分析。我们的结果表明，所有 β 细胞对胰岛生长和维持的贡献均等。发现胰腺 β 细胞池的复制能力是同质的。这表明所有 β 细胞都是替代疗法所需的体外扩增的候选细胞。
In healthy adult mice, the β cell population is not maintained by stem cells but instead by the replication of differentiated β cells. It is not known, however, whether all β cells contribute equally to growth and maintenance, as it may be that some cells replicate while others do not. Understanding precisely which cells are responsible for β cell replication will inform attempts to expand β cells in vitro, a potential source for cell replacement therapy to treat diabetes. Two experiments were performed to address this issue. First, the level of fluorescence generated by a pulse of histone 2B–green fluorescent protein (H2BGFP) expression was followed over time to determine how this marker is diluted with cell division; a uniform loss of label across the entire β cell population was observed. Second, clonal analysis of dividing β cells was completed; all clones were of comparable size. These results support the conclusion that the β cell pool is homogeneous with respect to replicative capacity and suggest that all β cells are candidates for in vitro expansion. Given similar observations in the hepatocyte population, we speculate that for tissues lacking an adult stem cell, they are replenished equally by replication of all differentiated cells. The β cells of the pancreas are responsible for insulin production and their destruction results in type I diabetes. β cell maintenance, growth, and regenerative repair is thought to occur predominately, if not exclusively, through the replication of existing β cells, not via an adult stem cell. It was previously unknown, however, whether all β cells divide at the same rate, or if multiple subpopulations of β cells exist, some highly replicative and others very slowly dividing, possibly postmitotic. We performed two types of experiments to determine whether all β cells are alike: label-retaining analysis and clonal analysis. Our results indicate that all β cells contribute equally to islet growth and maintenance. The pancreatic β cell pool is found to be homogeneous with respect to replicative capacity. This suggests that all β cells are candidates for the in vitro expansion required for replacement therapies.
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