科学家造出人类原始生殖细胞 不孕不育者新希望

外媒称,因不孕不育而烦恼的全世界几千万男女迎来新的希望。英国剑桥大学和以色列魏茨曼科学研究所组成的共同研究组当地时间24日在国际学术杂志《细胞(Cell) 》网络版宣布:“首次成功利用人类皮肤细胞制造出干细胞,这种干细胞可分化发育成精子和卵子。”据韩国《朝鲜日报》网站12月26日报道,据科学界期待这项研究取得成果后,即使因接受癌症治疗、绝经等原因无法生成精子和卵子,也可利用自身皮肤细胞随时拥有孩子。

但是,如果利用同一个人的细胞同时获得精子和卵子,可能会有人试图制造法律上禁止的克隆人。

研究组在人类皮肤细胞中注入可让细胞分阶段发育的基因。这样就使皮肤细胞变成可以发育成人体所有细胞的诱导多能干细胞(iPS细胞)。可以说皮肤细胞实现了返老还童。研究组成功在细胞中注入可以诱导其分化为生殖细胞的蛋白质等物质,使其可以分化发育为精子和卵子。

日 本科学家2012年曾利用相同方法从老鼠皮肤细胞中获得精子和卵子,并成功培育出健康幼崽。和当时相比,此次只能算是成功了一半。当时研究组将可以发育为 精子和卵子的细胞植入生殖器官——雌鼠卵巢和雄鼠精巢中,使其分别发育为卵子和精子。此后也有很多科学家对人体细胞进行了相同试验,但均以失败告终。

魏茨曼科学研究所博士雅各布·汉娜表示:“人类的诱导多能干细胞很容易发育成其他细胞,研究工作十分困难。和过去进行的老鼠试验一样,我们利用各种信号物质和诱导发育蛋白质使细胞保持稳定状态,分化成功率达到40%以上。”

研究组期待利用皮肤细胞培育出精子和卵子后,给不孕不育研究领域提供巨大帮助。但对于利用这种精子和卵子做试管婴儿,研究组持慎重态度。

汉娜当天接受国际学术杂志《自然》采访时表示:“我们计划在论文出版后观望社会对我们这项研究的看法。“

干 细胞研究涉及到破坏受精卵等伦理问题。但此次这项研究中的核心细胞——诱导多能干细胞没有使用受精卵,因此全世界都在积极开展这项研究。今年9月首次完成 了利用诱导多能干细胞的临床试验。日本理化学研究所成功给患有眼部疾病的70多岁女性移植了用诱导多能干细胞造出的网膜细胞,目前正在观察效果。

胚状体中的绿色细胞表明存在SOX17基因。

已经分化成原始生殖细胞状态(染色的细胞)的人类胚胎干细胞群。不同颜色表示不同基因的表达,从左至右分别是(l-r) NANOS3, NANOG, OCT4三个基因,第4张图中结合了全部三个基因。

新浪科技讯 北京时间26日消息,据国外媒体报道,近日,来自剑桥大学和以色列魏茨曼科学研究所的科学家宣布,他们利用人类胚胎干细胞,首次制造出了人类原始生殖细 胞。这种细胞可发育成卵子和精子。在此之前,科学家已经利用小鼠干细胞获得了原始生殖细胞,但这是第一次有效利用人类干细胞获得的结果。他们的研究发表在 近日的《细胞》(Cell)杂志上。

卵细胞在受精后,会开始分裂成囊胚,即胚胎的早期阶段。在囊胚中,一些细胞形成了内细胞团(将发育成胎儿),另一些则形成外壁(最后变成胎 盘)。内细胞团的细胞会“重新设定”成干细胞,具有发育成身体各种类型细胞的潜力。这些细胞中的一小部分会变成原始生殖细胞(primordial germ cells,PGCs),具有分化成为生殖细胞(精子和卵子)的潜力。

“原始生殖细胞的产生是哺乳动物发育早期的最初事件之一,”论文第一作者、剑桥大学威康信托/英国格登癌症研究所的Naoko Irie博士说,“利用小鼠和大鼠的干细胞,我们可以重建这一阶段,但直到现在,只有很少几个研究能利用人类干细胞进行同样的系统性工作。这强调了在人类 和啮齿类的胚胎发育中,存在着重要的差异;在小鼠和大鼠实验中的结果并不能直接外推到人类身上。”

格登癌症研究所的Surani教授领导了此次研究,他和同事们发现,一个名为SOX17的基因在指导人类干细胞分化为原始生殖细胞的过程中,起 着至关重要的作用。这是个令人惊讶的发现,因为在小鼠体内,这种基因与原始生殖细胞分化并没有关系。这一结果也表明,小鼠和人类发育中存在着关键差异。之 前的研究已经显示,SOX17基因与干细胞发育成内胚层细胞有关。内胚层细胞会发育成包括肺部、肠道和胰脏等器官的细胞。这是首次在原始生殖细胞分化中发 现SOX17基因的存在。

研究结果还表明,原始生殖细胞可以由重编码的成年细胞,如皮肤细胞获得。这也使对患者特异性细胞的研究成为可能,从而增加对人类生殖、不孕不育 和生殖细胞瘤的了解。另一方面,该研究也可以为理解“表征遗传”(epigenetic)过程提供潜在的帮助。科学家已经知道,我们的饮食、吸烟等习惯会 通过甲基化的过程,影响我们的基因活性。这种甲基化模式可以遗传给后代。

Surani教授及其同事的研究表明,在原始生殖细胞的分化阶段,会启动一个消除这些甲基化模式的程序,就像“重置”按钮一样。不过,这些甲基化模式的痕迹依然会遗传下去,其发生的原因目前尚不清楚。

“从某种意义上,生殖细胞是‘不朽’的,因为它们提供了代际间持续的连接,不断将这一代的遗传信息传递给下一代,”Surani教授说,“表征 遗传信息的全面消除可以保证大部分(如果不是所有的)表征突变被消除,从而使生物世系‘返老还童’,使无穷无尽的世系更迭成为可能。理解这些机制,可以为 研究与年龄有关的疾病带来益处,这些疾病的部分成因便是表征突变的累积。

ahuizotl基因进行细胞选择延长苍蝇寿命

据科学日报报道,瑞士伯尔尼大学的科研小组通过激活摧毁不健康细胞的基因,极大的延长了果蝇的生命周期。这 一结果或开启人类抗衰老研究的新可能性。长生不老一直是人类的梦想。例如,在古代神话里,永生是区别人类和神的特征之一。近期,试图延长人类寿命的生物研 究主要使用的是老鼠或者苍蝇的生物体模型。瑞士伯尔尼大学细胞生物学学院的爱德华多•莫雷诺(Eduardo Moreno)带领的研究人员小组提出了一个新方法延长苍蝇的寿命,它是基于对苍蝇体内最好细胞的优先选择来实现。这项研究被发表在期刊《细胞学》上。

The scientists found that a gene called ahuizotl, or ‘azot’ acts like a sort of cellular quality control, helping to weed out unhealthy or malfunctioning cells. Fruit flies, like the one pictured, were given an extra copy of this gene that targets unhealthy cells. During tests the flies lived 60% longer lives

Read more: http://www.dailymail.co.uk/sciencetech/article-2913648/Have-scientists-Elixir-Youth-Gene-destroys-unhealthy-cells-extend-life-flies-60-cent.html#ixzz3PKxvicN4
Immortality has long been a dream for humans. For example, in many ancient mythologies, immortality is one of the traits that distinguishes humans from the gods. More recently, biological research has tried to prolong human lifespan using model organisms such as mice or flies. Researchers at the Institute of Cell Biology from the University of Bern in Switzerland, led by Eduardo Moreno, have developed a new method to extend lifespan of flies based on improved selection of the best cells within the body. Their work appeared in the journal Cell.
“Our bodies are composed of several trillion cells,” explains Moreno, “and during aging those cells accumulate random errors due to stress or external insults, like UV-light from the sun.” But those errors do not affect all cells at the same time and with the same intensity: “Because some cells are more affected than others, we reasoned that selecting the less affected cells and eliminating the damaged ones could be a good strategy to maintain tissue health and therefore delay aging and prolong lifespan.”
A cellular quality control mechanism
To test their hypothesis, the researchers used Drosophila melanogaster flies. The first challenge was to find out which cells within the organs of Drosophila were healthier. Morenos team identified a gene which was activated in less healthy cells. They called the gene ahuizotl (azot) after a mythological Aztec creature selectively targeting fishing boats to protect the fish population of lakes, because the function of the gene was also to selectively target less healthy or less fit cells to protect the integrity and health of the organs like the brain or the gut.
Normally, there are two copies of this gene in each cell. By inserting a third copy, the researchers were able to select better cells more efficiently. The consequences of this improved cell quality control mechanism were, according to Moreno, “very exciting”: The flies appeared to maintain tissue health better, aged slower and had longer lifespans. “Our flies had median lifespans 50 to 60 percent longer than normal flies,” said Christa Rhiner, one of the authors of the study.
Could azot also slow down the human aging process?
However, the potential of the results goes beyond creating Methuselah flies, the researchers say: Because the gene azot is conserved in humans, this opens the possibility that selecting the healthier or fitter cells within organs could in the future be used as an anti aging mechanism. For example, it could prevent neuro- and tissue degeneration produced in our bodies over time.

瑞士伯尔尼大学爱德华多•莫雷诺的研究小组提出了一个新方法延长苍蝇的寿命

“我 们的身体是由几万亿个细胞组成,” 莫雷诺解释道。“在衰老过程中,这些细胞会积累因压力或外界刺激,例如太阳的紫外线光,而产生的随机错误。”但这些细胞并不会以相同的程度同时影响所有细 胞。“有些细胞比其它细胞更容易受到影响,我们由此推断选择影响较小的细胞,并消灭受损细胞应该是维持组织健康从而延缓衰老和延长寿命的好策略。”

细胞质量控制机制

为 了测试他们的假说,研究人员使用了黑腹果蝇(Drosophila melanogaster)作为实验对象。第一个面临的挑战便是找出黑腹果蝇器官里更健康的细胞。莫雷诺研究小组鉴别了在不那么健康的细胞里激活的基因, 他们将这个基因称为水猴ahuizotl(azot),以中美洲神话中的食人水怪Aztec为名,这个神话生物会选择性的攻击渔船以保护湖泊里的鱼类,而 这一基因的功能也是选择性的攻击不那么健康或者不太合适的细胞以保护器官,例如大脑和内脏的完整性和健康。

正 常来说,每一个细胞里有这个基因的两份副本。通过插入第三份副本,研究人员能够更高效的选择更好的细胞。莫雷诺表示这个改善细胞质量控制机制“令人感到兴 奋”,苍蝇似乎能够更好的维持组织健康,衰老的更慢,且具有更长的寿命。“我们的苍蝇的寿命比正常苍蝇长了50%至60%,”研究合作作者之一、伯尔尼大 学细胞生物学讲师克里斯塔•莱茵(Christa Rhiner)博士这样说道。

Azot是否也能减缓人类衰老过程?

然而,这一结果的潜在可能性远不止如此,研究人员表示由于人类体内也保存有Azot,这开启了一种新的可能性:也即在未来将选择更健康或者更合适的细胞作为一种抗衰老机制。例如,它可以预防人类身体随着衰老而产生的神经或者组织恶化。

Refereance:

Elimination of Unfit Cells Maintains Tissue Health and Prolongs Lifespan

Highlights
•Fitness-based cell culling maintains tissue health
•Azot ensures the elimination of less fit cells
•Lack of azot accelerates tissue degeneration
•Improving the efficiency of cell selection extends lifespan
Summary
Viable yet damaged cells can accumulate during development and aging. Although eliminating those cells may benefit organ function, identification of this less fit cell population remains challenging. Previously, we identified a molecular mechanism, based on “fitness fingerprints” displayed on cell membranes, which allows direct fitness comparison among cells in Drosophila. Here, we study the physiological consequences of efficient cell selection for the whole organism. We find that fitness-based cell culling is naturally used to maintain tissue health, delay aging, and extend lifespan in Drosophila. We identify a gene, azot, which ensures the elimination of less fit cells. Lack of azot increases morphological malformations and susceptibility to random mutations and accelerates tissue degeneration. On the contrary, improving the efficiency of cell selection is beneficial for tissue health and extends lifespan.

 

药明康德收购NextCODE成立WuXi NextCODE Genomics公司

NextCODE and WuXi’s Genome Center will offer comprehensive clinical, research, and diagnostic testing products and services worldwide
PR Newswire WuXi PharmaTech (Cayman) Inc. 13 hours ago
SHANGHAI, Jan. 9, 2015 /PRNewswire/ — WuXi PharmaTech (Cayman) Inc. (NYSE: WX), a leading open-access R&D capability and technology platform company serving the pharmaceutical, biotechnology, and medical device industries with operations in China and the United States, announces that it has acquired NextCODE Health, a leading genomic analysis and bioinformatics company with operations in the United States and Iceland, for $65 million in cash.  WuXi plans to merge NextCODE Health and WuXi’s Genome Center into a new company to be named WuXi NextCODE Genomics. The business will be headquartered in Shanghai, with operations in Cambridge, Massachusetts, and Reykjavik, Iceland. The leadership of WuXi NextCODE Genomics will include Dr. Ge Li as CEO, Edward Hu as CFO, Hannes Smarason as COO, Dr. Jeffrey Gulcher as CSO, Dr. Hongye Sun as CTO, and Dr. Hakon Gudbjartsson as VP Informatics.

NextCODE Health was spun out from deCODE genetics after the latter was acquired by Amgen in December 2012. Founded in 1996, deCODE genetics is a global leader in analyzing and understanding the links between the genome and disease susceptibility. Using its unique expertise and population resources in Iceland, deCODE genetics has discovered genetic risk factors for dozens of diseases ranging from cardiovascular disease to cancer. In October 2013, NextCODE Health announced that it had obtained from Amgen a five-year exclusive license for sequence-based clinical diagnostic applications using technology developed by deCODE genetics.

NextCODE Health has developed the world’s leading genome sequence analysis platform and the most efficient database architecture, enabling clinicians and researchers around the globe to use the full power of next-generation sequencing data to better diagnose and treat diseases. The company’s solutions combine the only whole genome analysis system developed at population scale with access to the largest clinical genetics reference database in the world. These capabilities give clinicians and researchers the ability to store, visualize, and analyze all of their genetic data at base-by-base resolution, in real time, from any browser; to collaborate with other clinicians and researchers; and thereby to solve more medical cases more efficiently.

The WuXi Genome Center was established in 2011 to provide next-generation sequencing solutions to academics, the life science industry, and medical institutions to advance personalized medicine. By integrating with WuXi AppTec’s full range of discovery and development services for the biopharmaceutical industry, the WuXi Genome Center provides a complete solution for drug development projects from target discovery and preclinical and clinical development to personalized medicine. The center meets international clinical standards and is the only CLIA-certified clinical genomics laboratory in China. WuXi Genome Center has ten Illumina HiSeq X sequencing machines in operation. In addition to offering sequencing services, WuXi’s genomics lab also provides assay development, validation, and testing services.

This acquisition lays the groundwork for the creation of an integrated global enterprise with unique advantages for applying genomics to medicine. It broadens and enhances WuXi’s existing genomic laboratory services for biopharmaceutical research and clinical development, as well as NextCODE’s unique capabilities in genome analysis. It provides global commercial customers of both entities with comprehensive genomic and bioinformatic capabilities, from CLIA-certified whole genome and whole exome sequencing to the analysis and interpretation of that sequencing data necessary to provide effective diagnosis and treatment.

This acquisition also represents an important step forward in WuXi’s development. For the first 14 years of its history, WuXi has served companies in the worldwide pharmaceutical, biotechnology, and medical device industries as they discover and develop new healthcare products. The acquisition will enable WuXi to broaden its customer base to doctors and patients. This is very important for WuXi’s vision to enable anyone and any company to discover and develop healthcare products and services to benefit patients.

“With the huge unmet medical needs in diseases with a genetic component and the rapid advances in genomics and bioinformatics, now is the right time for WuXi to make a strategic investment in this field, and NextCODE is the right partner,” said Dr. Ge Li, Chairman and CEO of WuXi PharmaTech. “This new venture of WuXi NextCODE Genomics will create important new genomic and bioinformatic products and services to help make personalized treatment and medicine a reality.  It will also enable doctors to provide better treatments to patients.”

“With this transaction, WuXi and NextCODE will deploy the unique advantages of their combined platform in virtually every major application of genomics worldwide,” said Hannes Smarason and Jeffrey Gulcher, co-founders of NextCODE Health. “In WuXi, we have a superior partner with strengths, including CLIA-certified sequencing and leading global pharmaceutical customers with a strong need for companion diagnostics, that are highly complementary to those of NextCODE. Together, WuXi and NextCODE have the technology, vision, and resources to be a leader in the sequencing revolution for the benefit of patients and for the advancement of medicine around the world.”

About WuXi PharmaTech

WuXi PharmaTech (NYSE: WX) is a leading open-access R&D capability and technology platform company serving the pharmaceutical, biotechnology, and medical device industries, with operations in China and the United States. As a research-driven and customer-focused company, WuXi PharmaTech provides pharmaceutical, biotechnology, and medical device companies with a broad and integrated portfolio of laboratory and manufacturing services throughout the drug and medical device R&D process. WuXi PharmaTech’s services are designed to help its global partners in shortening the cycle and lowering the cost of drug and medical device R&D. WuXi is also building a platform to provide clinical diagnostic services directly to physicians and their patients globally. The operating subsidiaries of WuXi PharmaTech are known as WuXi AppTec. For further information, please visit http://www.wuxiapptec.com.

About NextCODE Health

NextCODE Health was co-founded in 2013 by former deCODE genetics executives Jeffrey Gulcher and Hannes Smarason as a spinout from deCODE genetics after the latter was acquired by Amgen in December 2012. NextCODE Health is headquartered in Cambridge, Massachusetts, and has operations in Reykjavik, Iceland. The company has developed the world’s most proven gene sequence analysis platform and the most efficient database architecture, enabling clinicians and researchers around the globe to use the full power of next-generation sequencing data to better diagnose and treat disease. The company’s solutions combine the only whole genome analysis system developed at population scale with access to the largest clinical genetics reference database in the world. For further information, please visit http://www.nextcode.com.