更接近人类的小鼠胚胎干细胞培育成功

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方兴未艾的干细胞研究领域又有新成果。来自英国和美国的两个独立研究小组6月27日分别在《自然》杂志在线发表论文指出，他们成功培养了一种名为EpiSC的新型小鼠胚胎干细胞。该种新型干细胞比现有的小鼠胚胎干细胞更接近人类，它的培养成功将有助于人们更好地理解人类细胞生长和分化的过程。

  领导这两个小组的分别是来自美国国立神经紊乱与中风研究所（U.S. National Institute of Neurological Disorders and Stroke）的Ronald McKay以及来自英国剑桥大学的Roger Pedersen和Ludovic Vallier，他们的实验对象分别是小鼠和大鼠。

  研究人员将受精卵植入小鼠子宫5天半后，就可从其外胚层分离得到EpiSC细胞。这是一种全新的多能性细胞，能够分化成各种组织。与传统的小鼠胚胎干细胞不同，该种细胞与人类的胚胎干细胞更为相似。比如，二者都需要关闭LIF（一种白血病抑制因子）以更好地分化，二者的基因表达和细胞表面标记的模式也基本相同。McKay认为，该种细胞代表了进化的更高级阶段，就好像是传统小鼠胚胎干细胞和已开始分化胚胎干细胞之间那条“丢失的链条”。他说：“绝大多数人都认为，将受精卵植入子宫后是无法分离出多能性细胞系的。”但是事实并非如此。

  至于大鼠的EpiSCs，Pedersen表示其与小鼠的很类似，并且预言科学家未来将能够从绝大多数甚至全部的哺乳动物胚胎内分离出这种细胞。他认为，从EpiSC分化出的细胞系有助于促进人类胚胎干细胞向组织的分化并用于疾病的治疗。

  来自斯坦福大学的干细胞学家Renee Reijo Pera乐观地认为，该种新型细胞的培养成功将有助于阐明人类胚胎干细胞的活动过程。她说，这项研究表明，科学家将有可能制造出具有专门应用目的的新型胚胎干细胞。（引自科学网）


原始出处:

文章（一）：

Nature advance online publication 27 June 2007 | doi:10.1038/nature05972; Received 30 April 2007; Accepted 31 May 2007; Published online 27 June 2007


New cell lines from mouse epiblast share defining features with human embryonic stem cells
Paul J. Tesar1,2,4, Josh G. Chenoweth1,4, Frances A. Brook2, Timothy J. Davies2, Edward P. Evans2, David L. Mack3, Richard L. Gardner2 & Ronald D. G. McKay1

Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA
Mammalian Development Laboratory, Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK
Stem Cell Biology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
These authors contributed equally to this work.
Correspondence to: Paul J. Tesar1,2,4Ronald D. G. McKay1 Correspondence and requests for materials should be addressed to R.D.G.M. (Email: mckayr@ninds.nih.gov) and P.J.T. (Email: paultesar@ninds.nih.gov).


Abstract
The application of human embryonic stem (ES) cells in medicine and biology has an inherent reliance on understanding the starting cell population. Human ES cells differ from mouse ES cells and the specific embryonic origin of both cell types is unclear. Previous work suggested that mouse ES cells could only be obtained from the embryo before implantation in the uterus1, 2, 3, 4, 5. Here we show that cell lines can be derived from the epiblast, a tissue of the post-implantation embryo that generates the embryo proper. These cells, which we refer to as EpiSCs (post-implantation epiblast-derived stem cells), express transcription factors known to regulate pluripotency, maintain their genomic integrity, and robustly differentiate into the major somatic cell types as well as primordial germ cells. The EpiSC lines are distinct from mouse ES cells in their epigenetic state and the signals controlling their differentiation. Furthermore, EpiSC and human ES cells share patterns of gene expression and signalling responses that normally function in the epiblast. These results show that epiblast cells can be maintained as stable cell lines and interrogated to understand how pluripotent cells generate distinct fates during early development.

文章（二）：

Nature advance online publication 27 June 2007 | doi:10.1038/nature05950; Received 15 January 2007; Accepted 24 May 2007; Published online 27 June 2007


Derivation of pluripotent epiblast stem cells from mammalian embryos
I. Gabrielle M. Brons1, Lucy E. Smithers2, Matthew W. B. Trotter2, Peter Rugg-Gunn1,7, Bowen Sun1, Susana M. Chuva de Sousa Lopes3, Sarah K. Howlett4, Amanda Clarkson5, Lars Ahrlund-Richter6, Roger A. Pedersen1 & Ludovic Vallier1

Department of Surgery and Cambridge Institute for Medical Research, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0XY, UK
CR-UK Viral Oncology Group, Wolfson Institute for Biomedical Research, UCL, Cruciform Building Gower Street, London WC1E 6BT, UK
Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology and Department of Physiology, University of Cambridge, Tennis Court Road, Cambridge CB2, 1QR, UK
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, University of Cambridge, Cambridge CB2 0XY, UK
Medical Genetics Department Cambridge University Hospital NHS Foundation Trust, Kefford House Maris Lane Cambridge CB2 2FF, UK
Dept of Laboratory Medicine Clinical Research Centre, Karolinska University Hospital Karolinska Institutet 141 57 Stockholm, Sweden
Present address: Hospital for Sick Children, Toronto Medical Discovery Tower 101 College Street, Toronto, Ontario M5G 1L7, TMDT, Canada.
Correspondence to: Ludovic Vallier1 Correspondence and requests for materials should be addressed to L.V. (Email: lv225@cam.ac.uk).


Abstract
Although the first mouse embryonic stem (ES) cell lines were derived 25 years ago1, 2 using feeder-layer-based blastocyst cultures, subsequent efforts to extend the approach to other mammals, including both laboratory and domestic species, have been relatively unsuccessful. The most notable exceptions were the derivation of non-human primate ES cell lines3 followed shortly thereafter by their derivation of human ES cells4. Despite the apparent common origin and the similar pluripotency of mouse and human embryonic stem cells, recent studies have revealed that they use different signalling pathways to maintain their pluripotent status. Mouse ES cells depend on leukaemia inhibitory factor and bone morphogenetic protein, whereas their human counterparts rely on activin (INHBA)/nodal (NODAL) and fibroblast growth factor (FGF). Here we show that pluripotent stem cells can be derived from the late epiblast layer of post-implantation mouse and rat embryos using chemically defined, activin-containing culture medium that is sufficient for long-term maintenance of human embryonic stem cells. Our results demonstrate that activin/Nodal signalling has an evolutionarily conserved role in the derivation and the maintenance of pluripotency in these novel stem cells. Epiblast stem cells provide a valuable experimental system for determining whether distinctions between mouse and human embryonic stem cells reflect species differences or diverse temporal origins.