Interfollicular epidermal homeostasis: dicing with differentiation
Interfollicular epidermal homeostasis: dicing with differentiation
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DOI：
10.1111/j.1600-0625.2012.01447.x
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发表时间：
2012-04-01
影响因子：
3.6
通讯作者：
Jones, Philip H.
中科院分区：
文献类型：
--
作者：
Doupe, David P.;Jones, Philip H.
20 世纪 70 年代，组织结构和细胞增殖的研究被用来制定表皮稳态的新模型。这断言该组织是由寿命长、循环慢、自我更新的干细胞维持的，这些干细胞产生寿命短的转运扩增（TA）细胞群，这些细胞在一定次数的细胞分裂后经历终末分化。进一步假设，在表皮中，组织被组织成克隆表皮增殖单位（EPU），其包含中央干细胞和周围的TA细胞，其维持上覆的分化细胞层。 Stem/TA 和 EPU 假说具有广泛的影响力。在这里，我们首先重新评估旧文献，发现许多与 EPU 模型相冲突的研究。然后，我们回顾了最近在转基因小鼠中进行的大规模谱系追踪研究，这些研究排除了干/TA 和 EPU 假设，并揭示了表皮是由功能等效的循环祖细胞的单一群体维持的。单个祖细胞分裂的结果是随机的，但产生分化的祖细胞子代的概率是相等的，因此整个祖细胞群保持稳态。我们将这个模型与旧文献相一致，并将表皮置于其他组织的背景下，这些组织也由具有随机命运的不断循环的细胞维持。
In the 1970s, studies of tissue architecture and cell proliferation were used to formulate a new model of epidermal homeostasis. This asserted that the tissue was maintained by long-lived, slow-cycling, self-renewing stem cells that generate a short-lived population of transit amplifying (TA) cells, which undergo terminal differentiation after a set number of cell divisions. It was further hypothesized that in the epidermis, the tissue was organized into clonal epidermal proliferative units (EPUs) comprising a central stem cell with surrounding TA cells, which maintain the overlying differentiated cell layers. The stem/TA and EPU hypotheses have been widely influential. Here, we first revaluate older literature, finding numerous studies that conflict with the EPU model. We then review recent large-scale lineage tracing studies in transgenic mice which exclude the stem/TA and EPU hypotheses, and reveal that the epidermis is maintained by a single population of functionally equivalent cycling progenitor cells. The outcome of individual progenitor cell divisions is random, but the probabilities of generating differentiated and progenitor cell daughters are equal, so that homeostasis is maintained across the progenitor population. We reconcile this model with the older literature and place the epidermis in the context of other tissues that are also maintained by continually cycling cells with stochastic fate.