Germ cell specification and differentiation in planarians

来自成年小鼠睾丸的精原干细胞和来自新生小鼠睾丸的生殖干细胞可以产生具有类似于胚胎干细胞（ES细胞）的发育潜能的多能细胞。这些结果表明，来自睾丸的生殖细胞可用于为组织工程和再生医学提供干细胞。胚胎干细胞可能来源于生殖细胞的假说也提供了类似的动力 以了解指定和维持生殖细胞谱系的机制。目前对生殖细胞特化机制的理解主要基于对利用细胞质决定簇来特化其生殖细胞的模式生物的研究（例如，果蝇和C. elegans）。相反，许多生物（包括哺乳动物）利用诱导信号来指定生殖细胞的命运。归纳研究 规范几乎完全限于鼠标，且许多问题仍然没有答案。例如，是否存在指定生殖细胞命运的保守诱导信号？激活生殖细胞特异性基因表达模式的机制是什么？淡水真涡虫，Schmidtea medialacea，是研究这些问题的有用模型。它具有惊人的再生能力，基于一群干细胞，使其能够从一个微小的身体片段再生一个完整的动物;生殖细胞谱系也可以再生。这项工作将利用功能基因组工具可用于研究S。medialacea解剖诱导信号指定生殖细胞命运的机制。将进行微阵列分析，以确定具有早期生殖细胞的动物和缺乏早期生殖细胞的动物之间差异表达的基因。下一代测序技术将用于表征生殖细胞发育初始过程中的基因表达变化。高通量原位杂交将用于验证通过这些分析鉴定的候选基因。这些差异表达基因的功能将通过RNA干扰进行检测。这些研究 有可能确定生殖细胞正常发育所需的保守基因。

Spermatogonial stem cells from testes of adult mice and germline stem cells from testes of neonatal mice can generate pluripotent cells with developmental potential similar to embryonic stem (ES) cells. These results suggest that germ cells from the testes could be used to provide stem cells for tissue engineering and regenerative medicine. Hypotheses that ES cells may be derived from germ cells provide a similar impetus for understanding the mechanisms that specify and maintain the germ cell lineage. Current understanding of germ cell specification mechanisms is based largely upon studies of model organisms that utilize cytoplasmic determinants to specify their germ cells (e.g., Drosophila and C. elegans). In contrast, many organisms (including mammals) utilize inductive signals to specify germ cell fate. Studies of inductive specification have been limited almost exclusively to mouse and many questions remain unanswered. For example, are there conserved inductive signals that specify germ cell fate? What are the mechanisms that activate germ cell-specific patterns of gene expression? The freshwater planarian, Schmidtea mediterranea, serves as a useful model for studying these questions. It has prodigious regenerative abilities, based upon a population of stem cells, that allow it to regenerate a complete animal from a tiny body fragment; the germ cell lineage can also be regenerated. This work will capitalize on the functional genomic tools available for studying S. mediterranea to dissect the mechanisms by which inductive signals specify germ cell fate. Microarray analyses will be performed to identify genes that are expressed differentially between animals that have early germ cells and animals that lack them. Next generation sequencing technologies will be utilized to characterize gene expression changes during the initial course of germ cell development. High through put in situ hybridization will be used to validate candidate genes identified by these analyses. The functions of these differentially expressed genes will then be examined by RNA interference. These studies have the potential to identify conserved genes that are required for proper germ cell development.