体细胞直接重编程为神经元和神经干细胞

体细胞直接重编程是由已分化细胞类型不经过诱导型多能干细胞(Induced pluripotent stem cells,i PSCs)中间阶段,直接转换为另一种细胞类型的重编程过程。体细胞直接重编程避免了i PSC技术存在的重编程效率低下、引入致癌基因等多种缺陷,并为细胞替换治疗和个性化医药研发设想贡献了新的实现途径。现代医学对于诸如神经退行性疾病、神经遗传疾病和外伤导致的神经细胞受损等一些神经系统疾病一直没有有效的治疗手段。而体细胞直接重编程为治疗这些疾病提供了另一种治疗途径,因此体细胞直接重编程为神经细胞相关领域迅速成为研究热点。回顾了体细胞重编程为诱导型神经元(Induced neurons,i Ns)和诱导型神经干细胞(Induced neural stem cells,i NSCs)的最新研究进展,并探讨i Ns和i NSCs在临床应用上的各自优势、局限性及应用前景。     

体细胞重编程逆转为干细胞的研究进展

目前细胞和发育生物学上的研究成果为生物医学研究提供了广泛的前景.将完全分化的细胞重编程,不经过胚胎逆转为多能干细胞状态,这点燃了再生医学应用的新希望,这一成果从法律、道德、伦理等不同方面被人们所接受.通过体细胞克隆胚胎获得干细胞所面临的破坏胚胎的伦理限制,促使研究者去寻求将分化细胞重编程逆转为干细胞的新方法.主要论述了体细胞重编程的原理、过程及不经过胚胎逆转为多能干细胞的方法.     

Direct Reprogramming of Somatic Cells to Neurons: Pros and Cons of Chemical Approach

Neurochemical Research - Translating successful preclinical research in neurodegenerative diseases into clinical practice has been difficult. The preclinical disease models used for testing new...     

体细胞直接转化为多能干细胞的新方法

胚胎干细胞具有自我复制、高度增殖、多向分化潜能、可植入性和重建能力等特征.对于诸如青少年糖尿病、帕金森综合症和心脏病等需要通过细胞移植来治疗的疾病而言,从人的囊胚内细胞团获得胚胎干细胞系是最理想的供体来源.然而,目前实验和医疗还要考虑到利用人类胚胎的一些伦理问题和组织排异反应.避免这些问题的可能途径就是通过已分化体细胞的重新编程来直接转化为诱导性多能干细胞,它们具有类似ES细胞的功能.目前,获得诱导性多能干细胞的设想已初步实现了从老鼠到人的突破.以下主要对体细胞直接转化为诱导性多能干细胞的研究现状、方法和转录因子在诱导体细胞重新编程中发挥的作用等内容进行了概述,以期为干细胞研究者进行更深入的研究提供一定的借鉴.     

Direct Conversion of Fibroblasts to Neurons by Reprogramming PTB-Regulated MicroRNA Circuits

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Highlights? Diminished PTB expression is sufficient to trans-differentiate fibroblasts to neurons ? PTB plays a key role in a regulatory loop to suppress neuronal-specific genes ? PTB regulates gene expression at both the splicing and RNA stability levels ? PTB modulates microRNA targeting by competition or switching RNA structure     

脂肪来源干细胞体外成骨和成脂及成神经的诱导分化研究

目的:探讨脂肪来源干细胞体外成骨和成脂及成神经的诱导分化情况。方法:选取10只SPF级雄性SD大鼠,将其不同部位的脂肪组织取出,分别采用不同方法对其向成骨、成脂及成神经等方向进行诱导分化并对其结果进行鉴定。结果:ADSC表达中,CD29占(99.11±0.13)%,CD44占(95.94±0.71)%,CD45占(0.12±0.09)%。经4周的成骨诱导后,茜素红S染色在细胞团中央发现红色钙化结节存在,碱性磷酸酶染色在细胞的胞质内观察到紫红色颗粒,经7d成脂诱导后,油红"O"染色在细胞质内观察到橙红色脂滴;经过6d的神经干培养基诱导后,通过免疫荧光染色证明诱导的Nestin细胞、神经丝蛋白-200以及GFAP等均出现阳性表达。结论:ADSC具备向脂肪、成骨及神经元等细胞进行多向分化的潜能,具有来源广、易于操作、体外增殖快速等优越性,并且不存在免疫排斥及医学伦理学问题,发展前景广阔。     

Progranulin Facilitates Conversion and Function of Regulatory T Cells under Inflammatory Conditions

The progranulin (PGRN) is known to protect regulatory T cells (Tregs) from a negative regulation by TNF-α, and its levels are elevated in various kinds of autoimmune diseases. Whether PGRN directly regulates the conversion of CD4+CD25-T cells into Foxp3-expressing regulatory T cells (iTreg), and whether PGRN affects the immunosuppressive function of Tregs, however, remain unknown. In this study we provide evidences demonstrating that PGRN is able to stimulate the conversion of CD4+CD25-T cells into iTreg in a dose-dependent manner in vitro. In addition, PGRN showed synergistic effects with TGF-β1 on the induction of iTreg. PGRN was required for the immunosuppressive function of Tregs, since PGRN-deficient Tregs have a significant decreased ability to suppress the proliferation of effector T cells (Teff). In addition, PGRN deficiency caused a marked reduction in Tregs number in the course of inflammatory arthritis, although no significant difference was observed in the numbers of Tregs between wild type and PGRN deficient mice during development. Furthermore, PGRN deficiency led to significant upregulation of the Wnt receptor gene Fzd2. Collectively, this study reveals that PGRN directly regulates the numbers and function of Tregs under inflammatory conditions, and provides new insight into the immune regulatory mechanism of PGRN in the pathogenesis of inflammatory and immune-related diseases.     

Superior Cervical Ganglia Neurons Induce Foxp3+ Regulatory T Cells via Calcitonin Gene-Related Peptide

The nervous and immune systems communicate bidirectionally, utilizing diverse molecular signals including cytokines and neurotransmitters to provide an integrated response to changes in the body’s internal and external environment. Although, neuro-immune interactions are becoming better understood under inflammatory circumstances and it has been evidenced that interaction between neurons and T cells results in the conversion of encephalitogenic T cells to T regulatory cells, relatively little is known about the communication between neurons and naïve T cells. Here, we demonstrate that following co-culture of naïve CD4⁺ T cells with superior cervical ganglion neurons, the percentage of Foxp3 expressing CD4⁺CD25⁺ cells significantly increased. This was mediated in part by immune-regulatory cytokines TGF-β and IL-10, as well as the neuropeptide calcitonin gene-related peptide while vasoactive intestinal peptide was shown to play no role in generation of T regulatory cells. Additionally, T cells co-cultured with neurons showed a decrease in the levels of pro-inflammatory cytokine IFN-γ released upon in vitro stimulation. These findings suggest that the generation of Tregs may be promoted by naïve CD4⁺ T cell: neuron interaction through the release of neuropeptide CGRP.     

Genetic Dissection of Neural Properties using Somatic Cell Hybrids

A set of neuronal genes can be expressed in neuroblastoma × L cell hybrids and hybrid cell lines with specific defects in neural function can be generated in high yield.     

Early Cellular Events During Direct Somatic Embryogenesis in Cotyledon Explants of Solanum aviculare Forst.

A detailed light and electron microscope study of early cellularevents at the onset of somatic embryogenesis in cotyledon explantsof Solanum aviculare Forst., cultured on MS medium supplementedwith 1 mg l^–1 2,4-dichloro-phenoxyacetic acid (2,4-D)for periods of 0–12 d in darkness, is described. Examinationsof longitudinal sections in a plane offset from the centralveins indicated that the earliest embryogenic events in explantstook place within the first 3–4 d of culture in the parenchymacells associated with the vascular traces closest to the cutbasal ends of cotyledons. Thereafter, parenchyma associatedwith more distal vascular traces became active in an apparentlysequential manner such that, by the second week of culture,progressive stages of embryogenesis could be observed alongthe lengths of cotyledon sections. Despite the fact that epidermalcells and palisade tissues were exposed directly to the 2,4-Dmedium, initiation of embryogenic development was never observedin cells other than those directly associated with vasculartraces. None of the embryogenic events characterized at theultrastructural level were observed in cotyledons cultured onMS medium in the absence of 2,4-D with the exception that starchaccumulated in decreasing amounts from the wounded basal endto the distal end of each cotyledon. This system provides a valuable model with which to study earlybiochemical and molecular events occurring in explants duringthe onset of somatic embryogenesis because they occur in a predictablefashion at sequentially situated sites along the explant tissues. Somatic embryogenesis, Solanum aviculare, cotyledon explants, cellular changes     

体细胞克隆牛和转基因体细胞克隆牛的遗传学分析(英)

分析了来自同一细胞系的体细胞克隆牛甜甜、庆庆、浒娃及来源同一培养转基因体细胞系转基因体细胞克隆牛九妹、乐娃和1个妊娠8个月转基因流产胎牛8C2以及随机抽取的1头鲁西黄牛(LX)、1头褐斯坦牛(HS)在24个微卫星位点标记牛的基因型.结果表明24个多态位点均表现出多态,等位基因数为1～5个,平均为3.17个.根据网上公布的数据,按其最高频率计算,甜甜、庆庆、浒娃、九妹、乐娃、8C2与培养细胞系、转基因细胞系间匹配概率为1.17×10^－36,根据本研究观察到的数据计算,匹配概率为1.90×10^－23;而与随机抽取的1头鲁西黄牛及褐斯坦牛的基因型分别在23和20个位点上完全不同.     

脱落酸在植物体细胞胚胎发生中的调控作用

脱落酸是一种具有全面生理功能的植物激素,在植物体细胞胚胎发生发育过程中具有重要的作用。根据国内外最新的研究文献,从脱落酸对植物体细胞胚胎发生的影响、植物体细胞胚胎发生过程中内源脱落酸含量的变化、脱落酸对体细胞胚胎发生过程中基因表达、信号转导的调控和转基因的表达调控入手,概述了脱落酸在植物体细胞胚胎发生中的调控作用。