Transit-Amplifying Cell Frequency and Cell Cycle Kinetics Are Altered in Aged Epidermis
Transit-Amplifying Cell Frequency and Cell Cycle Kinetics Are Altered in Aged Epidermis
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DOI：
10.1038/jid.2009.127
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发表时间：
2009-11-01
影响因子：
6.5
通讯作者：
Ghadially, Ruby
中科院分区：
文献类型：
--
作者：
Charruyer, Alexandra;Barland, Chantal O.;Ghadially, Ruby
老化的表皮比年轻的表皮增殖性更低，如较慢的伤口愈合所例示的。然而，目前尚不清楚干细胞和/或转运扩增（TA）区室的定量和/或定性改变是否是导致增殖减少的原因。早期的研究发现，随着年龄的增长，假定的表皮干细胞（EpiSC）的频率正常或降低。我们表明，使用长期的体内再增殖和体外集落形成，即，虽然没有显着差异，检测到EpiSC的频率与老化，TA细胞的频率增加。此外，老化的TA细胞存活时间更长，而年轻的TA细胞已经分化。老年人TA细胞动力学改变的基础是周期性角质形成细胞比例的增加以及细胞周期持续时间的增加。总之，尽管没有发现EpiSC频率的显著差异，但TA细胞频率增加（如通过体内再增殖、生长分数和集落形成所测量的）。此外，与年轻细胞的增殖能力（细胞输出）相比，个体老年EpiSC和TA细胞的增殖能力（细胞输出）降低。虽然较长的细胞周期持续时间有助于减少增殖输出从老化的祖细胞，更大数量的TA细胞可能是一种补偿机制，往往抵消这种赤字。
Aged epidermis is less proliferative than young, as exemplified by slower wound healing. However, it is not known whether quantitative and/or qualitative alterations in the stem and/or transit-amplifying ( TA) compartments are responsible for the decreased proliferation. Earlier studies found a normal or decreased frequency of putative epidermal stem cells (EpiSCs) with aging. We show, using long-term repopulation in vivo and colony formation in vitro, that, although no significant difference was detected in EpiSC frequency with aging, TA cell frequency is increased. Moreover, aged TA cells persist longer, whereas their younger counterparts have already differentiated. Underlying the alteration in TA cell kinetics in the aged is an increase in the proportion of cycling keratinocytes, as well as an increase in cell cycle duration. In summary, although no significant difference in EpiSC frequency was found, TA cell frequency was increased ( as measured by in vivo repopulation, growth fraction, and colony formation). Furthermore, the proliferative capacity ( cellular output) of individual aged EpiSCs and TA cells was decreased compared to that of young cells. Although longer cell cycle duration contributes to the decreased proliferative output from aged progenitors, the greater number of TA cells may be a compensatory mechanism tending to offset this deficit.