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简介: 血液系统中贮藏着一种具有自我更新、分化成各种血细胞潜能的成体干细胞,称为造血干细胞,它能够维持机体长久造血和组织稳态。造血干细胞移植是恶性血癌的有效治疗手段,但干细胞来源不足成为限制该治疗广泛应用的瓶颈。因此,造血干细胞的发育,尤其是造血干细胞扩增的研究备受关注。然而,现在的研究主要集中在特定细胞群体或关键因子的“线性化”或“平面化”解析,缺乏全面“立体化”的分析。从系统生物学角度解析扩增性造血器官,将为造血干细胞扩增的机制研究提供更多的启示。鉴于造血发育过程的高度保守性,中国科学院动物研究所刘峰研究组及合作者以斑马鱼尾部造血组织(在功能上类似于哺乳动物的胎肝,为造血干细胞扩增及分化提供了特定的微环境)为研究对象,利用多重转录组测序的方法,绘制了扩增性造血器官的3D转录组图谱,阐释了造血干细胞和微环境细胞之间的分子调控网络。首先,为了系统性地研究斑马鱼尾部造血组织如何支持造血干细胞扩增、分化的机制,刘峰实验室利用三种转录组测序方法,特定类型群体细胞转录组、空间转录组和单细胞转录组,详细解析了斑马鱼尾部造血组织的时空特性。不同发育时期特定细胞群体的转录组测序分析表明,造血干细胞与相应微环
简介:  众所周知,血液系统具有维持机体稳态的重要功能,对生物体的免疫防御和组织发育起到至关重要的作用。造血系统异常会引发诸多恶性血液疾病,如白血病、贫血和再生贫血障碍等。造血干细胞因具有自我更新和分化为各系血细胞的能力,而成为治疗多种血液疾病的核心组分。因此,造血干细胞的体内发育和体外诱导扩增已成为当今科学界的研究热点。在脊椎动物发育过程中,造血干细胞首先由主动脉腹侧壁的生血内皮通过内皮-造血转化过程产生,随后通过自我更新与分化维持机体的终生造血。目前,虽已发现多个调控造血干细胞产生的关键基因和信号通路,但是,人们对于造血干细胞发育动态调控机制的了解仍不完善。中国科学院动物研究所研究员刘峰领导的血液与心血管发育研究组与国家生物医学分析中心张学敏/李慧艳团队合作,首次揭示中心体蛋白FSD1在纤毛发生中的作用。敲除FSD1导致纤毛发生和早期胚胎发育缺陷。深入机制探究发现,敲低FSD1或者其他微管锚定蛋白导致纤毛过渡区组装因子Cep290从中心卫星解离,阻止纤毛过渡区形成,进而影响纤毛发生(Nat Commun. 2018, 9(1):5277)。在此基础之上,研究人员充分利用斑马鱼胚胎活体观察的
简介:  3月13日,中国科学院生物物理研究所王晓群研究组在神经科学杂志The Journal of Neuroscience 发表了题为Cenpj regulates cilia disassembly and neurogenesis in the developing mouse cortex 的研究成果,该工作阐明了在小鼠大脑皮层发育过程中中心体蛋白Cenpj对体内纤毛解聚和神经发生的调控作用。头小畸形是一类神经系统发育型疾病,头小畸形患者的头部尺寸仅为正常同龄人的三分之一,伴有智力发育障碍、情绪失控等症状,严重影响患者的正常生活。导致头小畸形的突变大都是编码中心体蛋白的基因,该文关注一种导致头小畸形的中心体基因Cenpj,它不仅可以调控中心粒的生长,也可以控制细胞骨架结构。为了探讨人类Cenpj突变引起脑发育缺陷的病理机制,研究人员首先利用Cre-Loxp技术在小鼠的大脑皮层中特异性敲除Cenpj基因后得到Cenpj条件敲除小鼠(CenpjCKO)。这些小鼠稳定地出现了类似于头小畸形病人的病理特征,包括头小、皮层变薄、神经元数量减少的表型。该研究发现胚胎期的Cenpj条件敲除小鼠(C
简介: Artificial insemination is used to improve the genetics of dairy cattle, like this bull.Credit: Leonhard Foeger/ReutersReproductive biologists are developing an unusual way to produce farm animals with desirable traits: injecting surrogate fathers — whose own sperm production has been crippled by gene editing — with sperm-producing stem cells from another male that pass along ‘elite’ genes to offspring. From then on, the surrogate sire's offspring will not be his own, but the donor's.The goal is
简介: Rotator cuff tears are common injuries, and proper healing of the shoulder muscle is often difficult."Chronic tears often result in fat accumulation within the rotator cuff muscles, resulting in negative clinical outcomes, including weakening and atrophy of the muscles," Manuel Schubert, M.D., resident in orthopaedic surgery at Michigan Medicine, said. "It's believed that this process of fat infiltration makes rotator cuff muscle damage one of the most difficult to rehabilitate after injury."Sch
简介: These cloned macaque monkeys are almost genetically identical, and share a mutation that disrupts their sleep cycle. Credit: Institute of Neuroscience, Chinese Academy of SciencesResearchers around the world interested in unravelling the mechanisms of complex human disorders, such as Alzheimer’s disease, could soon have access to cloned monkeys with genomes that have been edited to display these conditions in China.On 24 January, scientists at the Institute of Neuroscience (ION) in Shanghai repo
简介: About 3.4 million Americans, or 1.2 percent of the population, have active epilepsy. Although the majority respond to medication, between 20 and 40 percent of patients with epilepsy continue to have seizures even after trying multiple anti-seizure drugs. Even when the drugs do work, people may develop cognitive and memory problems and depression, likely from the combination of the underlying seizure disorder and the drugs to treat it.A team led by Ashok K. Shetty, PhD, a professor in the Departm
简介: Mice do not naturally develop Alzheimer's disease. Credit: The Jackson LaboratoryDrug companies have spent billions of dollars searching for therapies to reverse or significantly slow Alzheimer’s disease, to no avail. Some researchers argue that the best way to make progress is to create better animal models for research, and several teams are now developing mice that more closely simulate how the disease devastates people’s brains.The US National Institutes of Health (NIH), the UK Dementia Rese
简介: If a new anti-cancer drug shows promise in a Petri dish, often the next step is to test the drug's effect in mice. This system tends to work well with drugs that directly target cancer, but breaks down with immunotherapies. That's because tumors from human cancer samples can only grow in mice with suppressed immune systems. Immunotherapies activate the immune system against cancer. And in a mouse model in which the immune system has been suppressed, there is no immune system to activate against
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