Cook Matthew S, Cazin Coralie, Amoyel Marc, Yamamoto Shinya, Bach Erika, Nystul Todd
Center for Reproductive Sciences, University of California, San Francisco, California 94143-0452.
Department of Anatomy, University of California, San Francisco, California 94143-0452.
Genetics. 2017 Jul;206(3):1417-1428. doi: 10.1534/genetics.117.201202. Epub 2017 May 16.
The process of selecting for cellular fitness through competition plays a critical role in both development and disease. The germarium, a structure at the tip of the ovariole of a ovary, contains two follicle stem cells (FSCs) that undergo neutral competition for the stem cell niche. Using the FSCs as a model, we performed a genetic screen through a collection of 126 mutants in essential genes on the chromosome to identify candidates that increase or decrease competition for the FSC niche. We identified ∼55 and 6% of the mutations screened as putative FSC hypo- or hyper-competitors, respectively. We found that a large majority of mutations in vesicle trafficking genes (11 out of the 13 in the collection of mutants) are candidate hypo-competition alleles, and we confirmed the hypo-competition phenotype for four of these alleles. We also show that and another COPII vesicle trafficking component, Sar1, are required for follicle cell differentiation. Lastly, we demonstrate that, although some components of vesicle trafficking are also required for neutral competition in the cyst stem cells of the testis, there are important tissue-specific differences. Our results demonstrate a critical role for vesicle trafficking in stem cell niche competition and differentiation, and we identify a number of putative candidates for further exploration.
通过竞争来选择细胞适应性的过程在发育和疾病中都起着关键作用。生殖腺是卵巢中卵巢管尖端的一种结构,包含两个卵泡干细胞(FSC),它们会对干细胞微环境进行中性竞争。以FSC为模型,我们通过对染色体上126个必需基因的突变体集合进行遗传筛选,以鉴定增加或减少对FSC微环境竞争的候选基因。我们分别将筛选出的约55%和6%的突变鉴定为假定的FSC低竞争或高竞争突变体。我们发现,囊泡运输基因中的大多数突变(突变体集合中的13个中有11个)是候选低竞争等位基因,并且我们证实了其中四个等位基因的低竞争表型。我们还表明,[此处原文缺失具体基因名称]和另一个COPII囊泡运输成分Sar1是卵泡细胞分化所必需的。最后,我们证明,尽管囊泡运输的一些成分在睾丸的囊干细胞的中性竞争中也是必需的,但存在重要的组织特异性差异。我们的结果证明了囊泡运输在干细胞微环境竞争和分化中的关键作用,并且我们鉴定出了一些有待进一步探索的假定候选基因。