Crittenden Sarah L, Leonhard Kimberly A, Byrd Dana T, Kimble Judith
Howard Hughes Medical Institute, Department of Biochemistry, Laboratory of Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Mol Biol Cell. 2006 Jul;17(7):3051-61. doi: 10.1091/mbc.e06-03-0170. Epub 2006 May 3.
The Caenorhabditis elegans germ line provides a model for understanding how signaling from a stem cell niche promotes continued mitotic divisions at the expense of differentiation. Here we report cellular analyses designed to identify germline stem cells within the germline mitotic region of adult hermaphrodites. Our results support several conclusions. First, all germ cells within the mitotic region are actively cycling, as visualized by bromodeoxyuridine (BrdU) labeling. No quiescent cells were found. Second, germ cells in the mitotic region lose BrdU label uniformly, either by movement of labeled cells into the meiotic region or by dilution, probably due to replication. No label-retaining cells were found in the mitotic region. Third, the distal tip cell niche extends processes that nearly encircle adjacent germ cells, a phenomenon that is likely to anchor the distal-most germ cells within the niche. Fourth, germline mitoses are not oriented reproducibly, even within the immediate confines of the niche. We propose that germ cells in the distal-most rows of the mitotic region serve as stem cells and more proximal germ cells embark on the path to differentiation. We also propose that C. elegans adult germline stem cells are maintained by proximity to the niche rather than by programmed asymmetric divisions.
秀丽隐杆线虫的生殖系为理解干细胞微环境发出的信号如何以牺牲分化为代价促进持续的有丝分裂提供了一个模型。在此,我们报告了旨在鉴定成年雌雄同体线虫生殖系有丝分裂区域内生殖系干细胞的细胞分析。我们的结果支持几个结论。第一,有丝分裂区域内的所有生殖细胞都在活跃地循环,这通过溴脱氧尿苷(BrdU)标记得以显现。未发现静止细胞。第二,有丝分裂区域内的生殖细胞均匀地失去BrdU标记,要么是通过标记细胞进入减数分裂区域,要么是通过稀释,可能是由于复制。在有丝分裂区域未发现标记保留细胞。第三,远端末梢细胞微环境延伸出几乎环绕相邻生殖细胞的突起,这种现象可能将最远端的生殖细胞锚定在微环境内。第四,即使在微环境的紧邻范围内,生殖系有丝分裂也没有可重复的定向。我们提出,有丝分裂区域最远端排的生殖细胞作为干细胞,而更靠近近端的生殖细胞则走上分化之路。我们还提出,秀丽隐杆线虫成年生殖系干细胞是通过靠近微环境而非程序性不对称分裂来维持的。