人类及小鼠胚胎干细胞的不同多能性状态

胚胎干细胞(embryonic stem cells,ESCs)是来源于早期胚胎的全能性细胞,在合适条件下具有分化为任何一类成体细胞的潜力。在小鼠中,根据细胞来源的胚胎发育时间,ESCs可以被分为原始态多能性(na(?)ve pluripotency)和始发态多能性(primed pluripotency)两种状态。这两种状态的细胞在发育上相互联系,具有不同的形态、信号依赖、发育性质、基因表达及表观遗传学性质,并且在特定的条件下可以相互转化。人类胚胎干细胞(human embryonic stem cells,hESCs)的发育潜能曾一度被认为低于小鼠胚胎干细胞(mouse embryonic stem cells,mESCs),直到人类原始态胚胎干细胞的发现证明了hESCs可以表现出与mESCs相似的性质。这对于人类胚胎发育的研究及ESCs在临床治疗上的实际应用都具有重要的意义。     

影响鸡原始生殖细胞分离克隆因素的研究(简报)

具有多向分化潜能的胚胎干细胞有两种来源:一是来自于早期胚胎内细胞团的胚胎干细胞(Em-bryonic Stem Cells,ESCs),另一种是来自于胚胎生殖腺原始生殖细胞(Primordial Germ Cells,PGCs)的胚胎生殖细胞(Embryonic Germ Cells,EGCs)。     

影响鸡原始生殖细胞分离克隆因素的研究（简报）

具有多向分化潜能的胚胎干细胞有两种来源：一是来自于早期胚胎内细胞团的胚胎干细胞(Em．bryonic Stem Cells,ESCs),另一种是来自于胚胎生殖腺原始生殖细胞(Primordial Germ Cells,PGCs)的胚胎生殖细胞(Embryonic Germ Cells,EGCs)。     

MicroRNA对胚胎干细胞的多能性网络调控

胚胎干细胞(Embryonic stem cells, ESCs)是一类能够无限增殖和诱导分化为多种类型细胞的干细胞。MicroRNA(miRNA)是一类内源性具有调控基因表达功能的非编码RNA, 在ESCs增殖和分化过程中起重要作用。MiRNA可以通过对ESCs多能性网络中的转录因子、细胞周期、表观遗传学、信号转导等方面调控, 促使ESCs维持多能性状态。文章重点综述了miRNA的生成过程、调控ESCs多能性的主要miRNA家族以及miRNA对ESCs多能性网络调控作用等内容。     

多能性胚胎干细胞与DNA甲基化的关系

胚胎干细胞是一种能够维持自我更新、具有无限扩增能力的多能性干细胞。灵长类多能干细胞（iPSCs）根据其发育能力、细胞形态、基因表达谱以及表观遗传学的差异分为初始态多能干细胞（pPSCs）和原始态多能干细胞（nPSCs）。nPSCs因其容易进行基因工程处理以及体内外再生出功能组织器官等优势而在临床潜在应用上备受关注,因而有效维持ESCs的原始状态对其用于基础及临床研究具有重要意义。nPSCs的线粒体活性和自我更新能力高于pPSCs,且这两种多能性干细胞在DNA甲基化等方面都存在明显差别,DNA甲基化在nPSCs的转化及代谢中起到重要的作用。本文综述了DNA甲基化对ESCs的作用,特别是维持原始态的作用。     

《细胞-干细胞》：研究者揭示维持胚胎干细胞自我更新分子机制

清华大学生命科学学院陈晔光研究组对转化生长因子-β（TGFβ）超家族信号通路在小鼠胚胎干细胞命运决定的分子机制方面进行了系统的研究。2012年2月3日,其研究组在《细胞》（Cell）子刊《细胞-干细胞》（Cell Stem Cell）发表了题为“BMP4 Signaling Actsvia Dual—Specificity Phosphatase 9 to Control ERK Activity in Mouse Embryonic Stem Cells”的研究论文,报道了胚胎干细胞如何维持自我更新能力的重要分子机制。     

灵长类原始态多能干细胞的研究与挑战

啮齿类和传统的灵长类多能干细胞(pluripotent stem cells,PSCs)在很多方面表现出不同的属性.根据发育阶段、克隆形态、信号依赖、线粒体代谢、嵌合能力、基因表达以及表观遗传等差异,哺乳动物干细胞多能性被分为原始态(Naive)和始发态(Primed)两种状态.啮齿类PSCs表现为Naive特性,而小鼠外胚层干细胞(epiblast stem cells,Epi SCs)和传统的灵长类PSCs表现为Primed特性.体外是否存在灵长类Naive PSCs是当前干细胞研究的一个关键性科学问题,开展非人灵长类PSCs的研究对于解决该问题起到至关重要的作用.最近几项研究通过各自的方法获得了不同的灵长类Naive-like PSCs,这些细胞在很多方面表现出类似于啮齿类PSCs的Naive特性.本文分析了啮齿类和灵长类胚胎发育差异性产生不同PSCs的可能机制,总结了本研究组和其他研究小组在灵长类干细胞多能性方面的研究进展以及原始态(Naive)和始发态(Primed)PSCs自我更新的调控机制差异最后,对灵长类干细胞多能性研究存在的问题进行了分析,对将来的研究重点进行了展望.     

iPSCs遗传稳定性与重编程机制的研究进展

诱导性多能干细胞(Induced pluripotent stem cells, iPSCs)是采用特定转录因子,将体细胞重编程为具有多能性的干细胞。iPSCs已成功由多种体细胞诱导出来,不仅具有发育多能性还能避免胚胎干细胞(Embryonic stem cells, ESCs)的伦理道德问题,已成为生命科学领域不可或缺的研究工具,具有广阔的应用前景。但获得高质量、遗传稳定的iPSCs是当前亟须解决的问题。文章对iPSCs重编程机制和遗传稳定性的研究进展进行了综述,以期为提高iPSCs的诱导效率、降低诱导成本、掌握iPSCs质量控制的关键点提供参考,从而推进多能性干细胞临床应用的发展。     

鸡胚卵巢源类ES细胞的培养和鉴定

<正>来源于原始生殖细胞(Primordial germ cells,PGCs)的胚胎生殖细胞(Embryonic germ cells,EGCs),与来自内细胞群的细胞一起统称为胚胎干细胞(Embryonic stem cells,ESCs),具有增殖能力强和可分化为机体所有细胞和组织的能力,在基础研究和转     

家畜诱导性多能干细胞研究进展

目前,家畜胚胎干细胞(Embryonic stem cells,ESCs)建系技术还不完善,很多大型家畜都未能建立ESCs系,这在很大程度上限制了家畜相关研究的开展。诱导性多能干细胞(Induced pluripotent stem cells,iPSCs)技术的建立,为迅速、高效的获得家畜多潜能干细胞提供了新方法。家畜iPSCs的建立,将推动家畜发育生物学、异种器官移植、人类疾病模型建立、家畜品种改良等研究。综述了家畜iPSCs技术的最新进展,并探讨了家畜iPSCs的应用前景。     

Different flavors of pluripotency, molecular mechanisms, and practical implications

Pluripotent stem cells (PSCs) have been classified into two distinct states: a primitive, naive LIF-dependent state represented by murine ESCs, and a primed bFGF-dependent state observed in murine and rat epiblast stem cells (EpiSCs). The vast similarities between EpiSCs and human ESCs suggest that, despite their blastocyst origin, human ESCs exist in a primed pluripotent state. Recent findings demonstrate that the naive and primed pluripotent states are interconvertible, even in human cells, and hint that growth factor-mediated Nanog expression may be an important factor regulating the balance between them.     

Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells

Pluripotent stem cells exist in naive and primed states, epitomized by mouse embryonic stem cells (ESCs) and the developmentally more advanced epiblast stem cells (EpiSCs; ref. 1). In the naive state of ESCs, the genome has an unusual open conformation and possesses a minimum of repressive epigenetic marks. In contrast, EpiSCs have activated the epigenetic machinery that supports differentiation towards the embryonic cell types. The transition from naive to primed pluripotency therefore represents a pivotal event in cellular differentiation. But the signals that control this fundamental differentiation step remain unclear. We show here that paracrine and autocrine Wnt signals are essential self-renewal factors for ESCs, and are required to inhibit their differentiation into EpiSCs. Moreover, we find that Wnt proteins in combination with the cytokine LIF are sufficient to support ESC self-renewal in the absence of any undefined factors, and support the derivation of new ESC lines, including ones from non-permissive mouse strains. Our results not only demonstrate that Wnt signals regulate the naive-to-primed pluripotency transition, but also identify Wnt as an essential and limiting ESC self-renewal factor.     

An ES-like pluripotent state in FGF-dependent murine iPS cells

Recent data demonstrates that stem cells can exist in two morphologically, molecularly and functionally distinct pluripotent states; a naïve LIF-dependent pluripotent state which is represented by murine embryonic stem cells (mESCs) and an FGF-dependent primed pluripotent state represented by murine and rat epiblast stem cells (EpiSCs). We find that derivation of induced pluripotent stem cells (iPSCs) under EpiSC culture conditions yields FGF-dependent iPSCs from hereon called FGF-iPSCs) which, unexpectedly, display naïve ES-like/ICM properties. FGF-iPSCs display X-chromosome activation, multi-lineage differentiation, teratoma competence and chimera contribution in vivo. Our findings suggest that in 129 and Bl6 mouse strains, iPSCs can dominantly adopt a naive pluripotent state regardless of culture growth factor conditions.Characterization of the key molecular signalling pathways revealed FGF-iPSCs to depend on the Activin/Nodal and FGF pathways, while signalling through the JAK-STAT pathway is not required for FGF-iPS cell maintenance. Our findings suggest that in 129 and Bl6 mouse strains, iPSCs can dominantly adopt a naive pluripotent state regardless of culture growth factor conditions.