Cell kinetic studies fail to identify sequentially proliferating progenitors as the major source of epithelial renewal in the adult murine prostate.
Cell kinetic studies fail to identify sequentially proliferating progenitors as the major source of epithelial renewal in the adult murine prostate.
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DOI：
10.1371/journal.pone.0128489
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Signoretti S
中科院分区：
文献类型：
--
作者：
Pignon JC;Grisanzio C;Carvo I;Werner L;Regan M;Wilson EL;Signoretti S
有证据表明，干细胞及其后代在前列腺的发育中起着重要作用。尽管干细胞也被认为在离体成人前列腺上皮中产生分化的后代，但在体内成人前列腺干细胞的队列以及成人前列腺上皮维持和再生的机制仍然存在高度争议。我们试图通过在连续给药两种胸腺嘧啶类似物后对连续复制的细胞进行体内追踪来解决这个难题。我们的研究结果表明，在正常的前列腺稳态中，顺序增殖的细胞以与随机过程一致的速率被检测到。这些发现表明，在体内，在稳态条件下，大多数成年前列腺上皮细胞并不代表少数特化祖细胞的后代，这些祖细胞产生顺序复制的转运扩增（TA）细胞，而是由随机细胞分裂形成的。同样，在雄激素介导的前列腺上皮退化/再生的一个周期后，再生过程中没有检测到快速循环的TA细胞。这些发现极大地增强了我们对前列腺上皮细胞更新调节机制的理解，并可能对确定增殖性前列腺疾病的起源细胞具有重要意义。
There is evidence that stem cells and their progeny play a role in the development of the prostate. Although stem cells are also considered to give rise to differentiated progeny in the adult prostate epithelium ex vivo, the cohort of adult prostate stem cells in vivo as well as the mechanisms by which the adult prostate epithelium is maintained and regenerated remain highly controversial. We have attempted to resolve this conundrum by performing in vivo tracing of serially replicating cells after the sequential administration of two thymidine analogues to mice. Our results show that, during normal prostate homeostasis, sequentially proliferating cells are detected at a rate that is consistent with a stochastic process. These findings indicate that in vivo, under steady-state conditions, most adult prostate epithelial cells do not represent the progeny of a small number of specialized progenitors that generate sequentially replicating transit-amplifying (TA) cells but are formed by stochastic cell division. Similarly, no rapidly cycling TA cells were detected during regeneration following one cycle of androgen-mediated involution/regeneration of the prostate epithelium. These findings greatly enhance our understanding of the mechanisms regulating prostate epithelial cell renewal and may have significant implications in defining the cell of origin of proliferative prostatic diseases.
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DOI：
10.1126/science.1189992
发表时间：
2010-07-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Goldstein AS;Huang J;Guo C;Garraway IP;Witte ON
通讯作者：
Witte ON
影响因子：
--
作者：
Liu, June;Pascal, Laura E.;Wang, Zhou
通讯作者：
Wang, Zhou
影响因子：
5.2
作者：
Goto, Ken;Salm, Sarah N.;Wilson, E. Lynette
通讯作者：
Wilson, E. Lynette
影响因子：
64.8
作者：
Dor, Y;Brown, J;Melton, DA
通讯作者：
Melton, DA
影响因子：
21.3
作者：
Ousset, Marielle;Van Keymeulen, Alexandra;Blanpain, Cedric
通讯作者：
Blanpain, Cedric