Stem cell autotomy and niche interaction in different systems

The best known cases of cell autotomy are the formation of erythrocytes and thrombocytes(platelets) from progenitor cells that reside in special niches. Recently, autotomy of stem cells and its enigmatic interaction with the niche has been reported from male germline stem cells(GSCs) in several insect species. First described in lepidopterans, the silkmoth, followed by the gipsy moth and consecutively in hemipterans, foremost the milkweed bug. In both, moths and the milkweed bug, GSCs form finger-like projections toward the niche, the apical cells(homologs of the hub cells in Drosophila). Whereas in the milkweed bug the projection terminals remain at the surface of the niche cells, in the gipsy moth they protrude deeply into the singular niche cell. In both cases, the projections undergo serial retrograde fragmentation with progressing signs of autophagy. In the gipsy moth, the autotomized vesicles are phagocytized and digested by the niche cell. In the milkweed bug the autotomized vesicles accumulate at the niche surface and disintegrate. Autotomy and sprouting of new projections appears to occur continuously. The significance of the GSC-niche interactions, however, remains enigmatic. Our concept on the signaling relationship between stem cell-niche in general and GSC and niche(hub cells and cyst stem cells) in particular has been greatly shaped by Drosophila melanogaster. In comparing the interactions of GSCs with their niche in Drosophila with those in species exhibiting GSC autotomy it is obvious that additional or alternative modes of stem cell-niche communication exist. Thus, essential signaling pathways, including niche-stem cell adhesion(E-cadherin) and the direction of asymmetrical GSC division- as they were found in Drosophila- can hardly be translated into the systems where GSC autotomywas reported. It is shown here that the serial autotomy of GSC projections shows remarkable similarities with Wallerian axonal destruction, developmental axon pruning and dying-back degeneration in neurodegenerative diseases. Especially the hypothesis of an existing evolutionary conserved "autodestruction program" in axons that might also be active in GSC projections appears attractive. Investigations on the underlying signaling pathways have to be carried out. There are two other well known cases of programmed cell autotomy: the enucleation of erythroblasts in the process of erythrocyte maturation and the segregation of thousands of thrombocytes(platelets) from one megakaryocyte. Both progenitor cell types- erythroblasts and megakaryocytes- are associated with a niche in the bone marrow, erythroblasts with a macrophage, which they surround, and the megakaryocytes with the endothelial cells of sinusoids and their extracellular matrix. Although the regulatory mechanisms may be specific in each case, there is one aspect that connects all described processes of programmed cell autotomy and neuronal autodestruction: apoptotic pathways play always a prominent role. Studies on the role of male GSC autotomy in stem cell-niche interaction have just started but are expected to reveal hitherto unknown ways of signal exchange. Spermatogenesis in mammals advance our understanding of insect spermatogenesis. Mammal and insect spermatogenesis share some broad principles, but a comparison of the signaling pathways is difficult. We have intimate knowledge from Drosophila, but of almost no other insect, and we have only limited knowledge from mammals. The discovery of stem cell autotomy as part of the interaction with the niche promises new general insights into the complicated stem cell-niche interdependence.

Interplay of RNA-binding proteins controls germ cell development in zebrafish

The specification of germ cells in zebrafish mostly relies on an inherited mechanism by which localized maternal determinants,called germ plasm,confer germline fate in the early embryo.Extensive studies have partially allowed the identification of key regulators governing germ plasm formation and subsequent germ cell development.RNA-binding proteins,acting in concert with other germ plasm components,play essential roles in the organization of the germ plasm and the specification,migration,maintenance,and differentiation of primordial germ cells.The loss of their functions impairs germ cell formation and causes sterility or sexual conversion.Evidence is emerging that they instruct germline development through differential regulation of mRNA fates in somatic and germ cells.However,the challenge remains to decipher the complex interplay of maternal germ plasm components in germ plasm compartmentalization and germ cell specification.Because failure to control the developmental outcome of germ cells disrupts the formation of gametes,it is important to gain a complete picture of regulatory mechanisms operating in the germ cell lineage.This review sheds light on the contributions of RNA-binding proteins to germ cell development in zebrafish and highlights intriguing questions that remain open for future investigation.

精原细胞向生殖干细胞和生殖细胞转化的机制研究

生殖干细胞是生殖细胞发育的早期阶段。生殖干细胞是一类特殊类型的成体干细胞,它不但具有干细胞的特性,还具有传递遗传信息的能力。本项目以阐明精原干细胞转换体系为中心,以研究精原干细胞向雌性生殖干细胞转换的机制为主线,揭示其复杂机制和探索其在性分化异常相关疾病机理研究中的应用。基于这一主线,我们首先根据前期研究结果建立了精原干细胞向雌性生殖干细胞体外转化体系,根据这一结果和技术平台以及前期研究已建立的体内转换小鼠模型,从表观遗传学、细胞代谢和细胞器重塑等角度揭示了精原干细胞向雌性生殖干细胞转化的机制。另一方面,利用已建立的体内转换小鼠模型和已建立的性分化异常疾病资源库和家系库等揭示了性分化异常及相关疾病发生机制。项目的实施为性分化异常相关疾病的防治提供理论依据和技术平台,为人类优生和出生缺陷的防治奠定基础。