Generative models: Human embryonic stem cells and multiple modeling relations

Model organisms are at once scientific models and concrete living things. It is widely assumed by philosophers of science that (1) model organisms function much like other kinds of models, and (2) that insofar as their scientific role is distinctive, it is in virtue of representing a wide range of biological species and providing a basis for generalizations about those targets. This paper uses the case of human embryonic stem cells (hESC) to challenge both assumptions. I first argue that hESC can be considered model organisms, analogous to classic examples such as Escherichia coli and Drosophila melanogaster. I then discuss four contrasts between the epistemic role of hESC in practice, and the assumptions about model organisms noted above. These contrasts motivate an alternative view of model organisms as a network of systems related constructively and developmentally to one another. I conclude by relating this result to other accounts of model organisms in recent philosophy of science.     

CD20-related signaling pathway is differently activated in normal and dystrophic circulating CD133+ stem cells

Among the heterogeneous population of circulating hematopoietic and endothelial progenitors, we identified a subpopulation of CD133⁺ cells displaying myogenic properties. Unexpectedly, we observed the expression of the B-cell marker CD20 in blood-derived CD133⁺ stem cells. The CD20 antigen plays a role in the modulation of intracellular calcium homeostasis through signaling pathways activation. Several observations suggest that an increase in intracellular calcium concentration ([Ca²⁺]_i) could be involved in the etiology of the Duchenne muscular dystrophy (DMD). Here, we show that a CD20-related signaling pathway able to induce an increase in [Ca²⁺]_i is differently activated after brain derived neurotrophic factor (BDNF) stimulation of normal and dystrophic blood-derived CD133⁺ stem cells, supporting the assumption of a “CD20-related calcium impairment-affecting dystrophic cells. Presented findings represent the starting point toward the expansion of knowledge on pathways involved in the pathology of DMD and in the behavior of dystrophic blood-derived CD133⁺ stem cells. Received 15 October 2008; received after revision 27 November 2008; accepted 05 December 2008     

肝癌细胞系Hep3B中CD133+细胞亚群的分离及其特性的研究

目的研究CD133在人肝癌细胞系Hep3B中的表达以及CD133+细胞的体外增殖、自我更新及体内成瘤能力,初步探讨肝癌中CD133+细胞亚群的干细胞特性。方法流式细胞仪检测未分选的Hep3B细胞中CD133+细胞表达情况;免疫磁珠分选技术纯化CD133+肿瘤细胞;MTT法检测CD133+细胞体外增殖能力;无血清培养纯化...     

Coaxing bone marrow stromal mesenchymal stem cells towards neuronal differentiation: progress and uncertainties

Multipotent adult stem cells capable of developing into particular neuronal cell types have great potential for autologous cell replacement therapy for central nervous system neurodegenerative disorders and traumatic injury. Bone marrow-derived stromal mesenchymal stem cells (BMSCs) appear to be attractive starting materials. One question is whether BMSCs could be coaxed to differentiate in vitro along neuronal or glial lineages that would aid their functional integration post-transplantation, while reducing the risk of malignant transformation. Recent works suggest that BMSCs could indeed be differentiated in vitro to exhibit some cellular and physiological characteristics of neural cell lineages, but it is not likely to be achievable with simple chemical treatments. We discussed recent findings pertaining to efforts in neuronal differentiation of BMSCs in vitro, and results obtained when these were transplanted in vivo. Received 19 January 2006; received after revision 24 February 2006; accepted 12 April 2006     

Stem cells and their niche: a matter of fate

Embryonic stem cells provide an in vitro model for developmental biologists to study cell fate decisions during ontogenesis, while somatic stem cells allow physiologists to understand tissue homeostasis in the adult. The behavior of stem cells is dependent on an intimate relationship with a supportive niche. This brief review highlights some of the most important recent trends in stem cell biology, focusing in particular on the supportive microenvironments for both embryonic and adult stem cells. Known intrinsic and extrinsic molecular players from the best-characterized stem cell types are summarized, illuminating a number of shared environmental cues among tissues originating from all three embryonic germ layers. Received 6 October 2005; received after revision 27 December 2005; accepted 17 January 2006     

(In)discrete charm of the polyembryony: Evolution of embryo cloning

Polyembryonic development, where multiple embryos are formed from a single zygote, evolved at least 15 times in six different phyla in animals. The mechanisms leading to polyembryony and the forces that shaped the evolution of the polyembryonic developmental program have remained poorly understood. Recent studies of the polyembryonic development in the endoparasitic wasp Copidosoma floridanum have revealed that the evolution of polyembryony is associated with the evolution of developmental novelties such as total cleavage, early specification of embryonic and extra-embryonic fates, and a specific cell proliferation phase. These changes cumulatively result in the formation of thousands of embryos from a single egg. Laser ablation studies and analysis of early cell fate specification have revealed that a single blastomere representing the progenitor of the primordial germ cell regulates the proliferation of the embryos. We propose that evolutionary changes in cell cleavage, cell interactions, and the cell-differentiation program, reminiscent of interactions between the germinal stem cell and stem cell niche in fly ovaries, underlies the evolution of polyembryony. Received 30 January 2007; received after revision 21 June 2007; accepted 11 July 2007     

A combined artificial chromosome-stem cell therapy method in a model experiment aimed at the treatment of Krabbe’s disease in the Twitcher mouse

Mammalian artificial chromosomes (MACs) are safe, stable, non-integrating genetic vectors with almost unlimited therapeutic transgene-carrying capacity. The combination of MAC and stem cell technologies offers a new strategy for stem cell-based therapy, the efficacy of which was confirmed and validated by using a mouse model of a devastating monogenic disease, galactocerebrosidase deficiency (Krabbe’s disease). Therapeutic MACs were generated by sequence-specific loading of galactocerebrosidase transgenes into a platform MAC, and stable, pluripotent mouse embryonic stem cell lines were established with these chromosomes. The transgenic stem cells were thoroughly characterized and used to produce chimeric mice on the mutant genetic background. The lifespan of these chimeras was increased twofold, verifying the feasibility of the development of MAC-stem cell systems for the delivery of therapeutic genes in stem cells to treat genetic diseases and cancers, and to produce cell types for cell replacement therapies. Received 29 July 2008; received after revision 22 September 2008; accepted 24 September 2008     

华南五针松幼茎发育研究

利用透射电子显微镜和光学显微镜对华南五针松(Pinuskwangtungensis)顶芽和一年生幼茎,进行形态结构和发育的观察,并进行细胞内淀粉粒含量的研究。结果表明,华南五针松幼茎在芽鳞形成后期,顶芽出现分区结构。顶芽细胞、幼茎细胞中,质体、线粒体、内质网等细胞器的分布、数量与其干旱生活的环境相适应。茎的皮层、初生木质部有树脂道分布,均为裂生型垂直树脂道,由莲座状排列的12～18个细胞发育而来。淀粉粒在树脂道发育成熟前后的动态变化与树脂的合成和分泌有一定的关系。随着各组织的发育完善,幼茎内薄壁细胞的淀粉粒呈现一个由无到丰富的动态变化。     

结直肠癌类器官的应用进展与挑战

 结直肠癌（CRC）是全球发病率最高的消化道肿瘤之一，严重威胁人类的健康。近年来，类器官技术取得了令人欣喜的进展，已成为结直肠癌发生机制和临床转化研究的重要新工具。回顾了结直肠癌生态位信号通路的变化，总结了类器官技术在结直肠癌建模、肿瘤微环境研究、药物筛选、个体化治疗等方面的应用进展，讨论了当前类器官面临的挑战，并从类器官培养技术标准化和工程技术应用等角度展望了类器官的未来发展方向。     

三峡山地不同林型冠层截留特征及再分配过程研究

森林冠层对降雨的截留和再分配是生态水文学的重要研究内容.截留过程因降雨特征、森林类型及立地环境存在差异.以三峡库区山地的暖性针叶林、落叶阔叶林和针阔叶混交林三种林型为研究对象，对比了2018年植物生长季(4—11月)56场降雨的再分配特征及影响因素.结果表明：1) 降雨在三种林型的再分配特征具有明显差异.暖性针叶林的透流量、树干径流量、林冠截留量分别占同期林外降雨的62.0%、7.2%、30.8%；落叶阔叶林分别占77.9%、3.5%、18.6%；针阔混交林分别占73.3%、2.7%、24%. 2) 再分配参数与降雨量的相关分析显示，三种林型下树干茎流量、透流量均与降雨量呈线性正相关关系，冠层截留量与降雨量呈幂函数关系. 3) 场次降雨特征也会影响再分配，大雨和暴雨时三种林型内降水再分配的动态过程存在明显差异.三种林型的降雨再分配过程因受降雨量、降雨强度等降雨特征和林冠结构的影响而产生差异.针阔叶混交林在强降雨条件下能够更有效地减缓降雨对地表土壤的强烈冲击，减少水土流失.