（12.20-12.31/2010）
恒峰g22国际集团:陶国新 
---2010再生科学年度进展 

 　　本次动态蕴含以下内容：耐力磨炼使心肌细胞增殖的机理；癌症干细胞基因表白高癌症医治了局差；无需象征实时观察活组织中分子活动；果蝇激活生殖细胞遗传基因来产生肿瘤；癌细胞自我覆灭与自我；さ男藕欧肿；微幼RNA表白模式的整体图谱分辨干细胞类别
。以及2010各期中出现过的比力凸起的几项再生科学进展的幼结
。

1. 耐力磨炼使心肌细胞增殖的机理
【提要】
人们都知路磨炼身段能够推进新陈代谢
，有益于心血管健全
，但此前科学家对活动到底若何影响心脏却所知甚少
。美国哈佛大学医学院的钻研人员日前汇报说
，他们初次闯辗视水平发现活动有益心脏健全的机理
，这一发现将有助于开发出医治心血管疾病的新疗法
。钻研人员通过幼鼠尝试发现
，时时活动能够使幼鼠体内的C/EBPβ转录因子水平显著降落
，其了局会推进幼鼠心脏肌肉细胞增殖
，有益于心脏成长
。此表
，钻研人员还发现
，体内C/EBPβ水平较低的幼鼠对心力衰竭拥有抵抗能力
。钻研人员暗示
，这项钻研对心脏肌肉再生的潜力有了深刻理解
。参加钻研的哈佛大学医学院教授安东尼·罗森茨魏希暗示
，通过这项钻研能够开发出针对那些无法活动的心脏病患者的疗法
。这项钻研成就颁发在新一期美国《细胞》杂志上
。（起源：新华社）

【点评】
　　该钻研所发现的心肌增殖机理同样有助于理解非药物方式实现组织再生的机造并推进此类天然再生步骤的推广
。

【原文摘录】Cell, Volume 143, Issue 7, 1072-1083, 23 December 2010
C/EBPβ Controls Exercise-Induced Cardiac Growth and Protects against Pathological Cardiac Remodeling
Pontus Boström, Nina Mann, Jun Wu, et al.
The heart has the ability to grow in size in response to exercise, but little is known about the transcriptional mechanisms underlying physiological hypertrophy. Adult cardiomyocytes have also recently been proven to hold the potential for proliferation, a process that could be of great importance for regenerative medicine. Using a unique RT-PCR-based screen against all transcriptional components, we showed that C/EBPβ was downregulated with exercise, whereas the expression of CITED4 was increased. Reduction of C/EBPβ in vitro and in vivo resulted in a phenocopy of endurance exercise with cardiomyocyte hypertrophy and proliferation. This proliferation was mediated, at least in part, by the increased CITED4. Importantly, mice with reduced cardiac C/EBPβ levels displayed substantial resistance to cardiac failure upon pressure overload. These data indicate that C/EBPβ represses cardiomyocyte growth and proliferation in the adult mammalian heart and that reduction in C/EBPβ is a central signal in physiologic hypertrophy and proliferation.

2. 癌症干细胞基因表白高癌症医治了局差
【提要】  
　　据美国物理学家组织网12月22日（北京功夫）报路
，斯坦福大学钻研人员通过对白血病干细胞的基因表白方式钻研发现
，癌症干细胞基因表白水平更高的病人比表白水平低的病人预后成效要差好多
，该发现初次通过临床数据证了然癌症干细胞概想
。医疗人员可据此预测群体病人的医治了局
，并援手开发新的临床疗法
。钻研颁发在12月22日的〖国医学会杂志》（JAMA）上
。几年前提出的癌症干细胞概想以为
，某些癌症发源于一幼撮自我更新能力很强的细胞
，这一幼撮细胞即是癌症干细胞
。这些癌症干细胞能不休补充天生新的癌症细胞
，癌症要彻底医治
，必须断根这些干细胞
。癌症干细胞匹敌医治已经在一些固状肿瘤和血癌的动物模型中得到验证
，固然有大量尝试室证据支持
，但至今还不足临床证据
。论文合著者、斯坦福癌症中心医务部艾什·埃里沙德和同事拉文达·马杰提今年9月曾在尝试室幼鼠中
，对非霍奇森淋巴瘤癌症干细胞表表发现的蛋白质CD47钻研发现
，CD47是癌症干细胞的“；ど　
，有了它
，好多药物对这些细胞无效
。CD47在其他几种癌症干细胞中也存在
。马杰提以为这些动物尝试中发现的证据在人体中也应该存在
。他们用两种能鉴别白血病干细胞的表表象征
，从7个白血病患者的肿瘤样本中分离出这些白血病干细胞
，将肿瘤干细胞和其他肿瘤细胞的基因表白方式进行了对比
，了局有52%的基因表白分歧
。癌症干细胞基因表白方式和正常的血液干细胞很类似
，不仅能自我更新
，还能像正常干细胞在必要时辰才割裂
。为了逃避那些针对迅速割裂细胞的传统医治步骤
，它会选择少量割裂
，埋伏着
，期待机遇“大张旗鼓”
。
　　钻研人员还对来自1000多位急性骨髓白血病病人的4组肿瘤样本进行了对比钻研
，发此刻“癌症干细胞基因高表白”和“医治了局差”之间存在很强的有关性
。在一组德国样本中
，高表白病人3年内殒命的绝对风险高达78%
，而低表白病人仅为57%
。同样
，无病生计率、某个时期再度恶化可能性、匹敌初次医治固执性等指标也如此
。论文第一作者、斯坦福大学癌症系统生物学中心安德鲁·简托斯暗示
，白血病干细胞的信号越强
，病人寿命越短
，病情恶化得越快
，医治成效就更差
。目前
，钻研幼组在持续钻研数据
，以最终从各类结合抗体疗法中确定哪些疗法对癌症干细胞高表白基因信号的病人最有效
。（起源：科技日报 颁布功夫：2010-12-23 10:20:47）

【点评】
　　该钻研发现了白血病干细胞基因的高表白与急性粒细胞白血病的医治成效差之间有独立的有关性
，但是并没有证明癌症干细胞是肿瘤发生的起因
。

【原文摘录】 JAMA. 2010;304(24):2706-2715. doi: 10.1001/jama.2010.1862
Association of a Leukemic Stem Cell Gene Expression Signature With Clinical Outcomes in Acute Myeloid Leukemia
Andrew J. Gentles, Sylvia K. Plevritis, Ravindra Majeti, Ash A. Alizadeh
Abstract
Context In many cancers, specific subpopulations of cells appear to be uniquely capable of initiating and maintaining tumors. The strongest support for this cancer stem cell model comes from transplantation assays in immunodeficient mice, which indicate that human acute myeloid leukemia (AML) is driven by self-renewing leukemic stem cells (LSCs). This model has significant implications for the development of novel therapies, but its clinical relevance has yet to be determined.
Objective To identify an LSC gene expression signature and test its association with clinical outcomes in AML.
Design, Setting, and Patients Retrospective study of global gene expression (microarray) profiles of LSC-enriched subpopulations from primary AML and normal patient samples, which were obtained at a US medical center between April 2005 and July 2007, and validation data sets of global transcriptional profiles of AML tumors from 4 independent cohorts (n = 1047).
Main Outcome Measures Identification of genes discriminating LSC-enriched populations from other subpopulations in AML tumors; and association of LSC-specific genes with overall, event-free, and relapse-free survival and with therapeutic response.
Results Expression levels of 52 genes distinguished LSC-enriched populations from other subpopulations in cell-sorted AML samples. An LSC score summarizing expression of these genes in bulk primary AML tumor samples was associated with clinical outcomes in the 4 independent patient cohorts. High LSC scores were associated with worse overall, event-free, and relapse-free survival among patients with either normal karyotypes or chromosomal abnormalities. For the largest cohort of patients with normal karyotypes (n = 163), the LSC score was significantly associated with overall survival as a continuous variable (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.08-1.22; log-likelihood P <.001). The absolute risk of death by 3 years was 57% (95% CI, 43%-67%) for the low LSC score group compared with 78% (95% CI, 66%-86%) for the high LSC score group (HR, 1.9 [95% CI, 1.3-2.7]; log-rank P = .002). In another cohort with available data on event-free survival for 70 patients with normal karyotypes, the risk of an event by 3 years was 48% (95% CI, 27%-63%) in the low LSC score group vs 81% (95% CI, 60%-91% ) in the high LSC score group (HR, 2.4 [95% CI, 1.3-4.5]; log-rank P = .006). In multivariate Cox regression including age, mutations in FLT3 and NPM1, and cytogenetic abnormalities, the HRs for LSC score in the 3 cohorts with data on all variables were 1.07 (95% CI, 1.01-1.13; P = .02), 1.10 (95% CI, 1.03-1.17; P = .005), and 1.17 (95% CI, 1.05-1.30; P = .005).
Conclusion High expression of an LSC gene signature is independently associated with adverse outcomes in patients with AML.

3. 无需象征实时观察活组织中分子活动
【提要】  
　　美国哈佛大学科学家将受激拉曼散射（SRS）显微镜和核磁共振成像（MRI）技术结合
，研造出一种最新的生物医学成像设备
，极大拓展了SRS显微镜的视野
。其速度之快精度之高
，如同“视频”
，足以使科学家直接目见分子在活组织中的活动
。钻研论文颁发在最新一期《科学》杂志上
。“此前
，SRS显微镜每分钟只能拍摄一幅画面
，用于活的动物某人体就太慢了
。”哈佛大学化学与化学生物学教授谢晓亮说
，“我们大大提高了采集数据的速度
，使拍摄达到了视频速度
。”钻研幼组还用这种新型SRS显微镜追踪药物在皮肤下的移动
，其能清澈显示出药物实时吸收情况
。如与内镜查抄术结合
，还能一层一层观察组织的三维结构
。新型SRS显微镜的工作道理是探测原子之间化学键的内涵震荡
，由于融合了MRI技术
，在透视深度上更适合拍摄体内器官和其他大指标
，既可宽泛用于拍摄器官和组织结构的静态图像
，也能在亚细胞水平以流动画面观察细胞中的蛋白质、脂质和水
。
　　同多种常用的观察生物分子的技术相比
，新型SRS显微镜优势显著
。它能采集分析照射生物样本的近30%激光
，比传统SRS显微镜逾越30倍；并且不必要插入荧光象征
，预防了绿色荧光象征蛋白质侵扰生物蹊径或压住较幼生物分子的问题
。此表
，传统的红表显微镜空间分辨率太低
，并必要给样本脱水；天然的拉曼显微镜必要很高的激光能量
，整体耗时很长
，在活样本中的利用受到限度；有关反斯托克拉曼散射显微镜在拍摄除了脂质以表的大无数分子时对比度不够
，而新型SRS显微镜都能突破这些局限
。钻研人员暗示
，新型SRS显微镜在医疗领域的利用远景辽阔
。好比
，手术之前必须将样本送检以用于组织分析
，这个过程约莫要花20分钟
，其间病人必要等在手术台上
，而新技术可提供实时扫描透视
，有助于加快表科手术
，断根肿瘤和其他危险
。谢晓亮说：“这一项目起头于11年前
，核磁共振技术花了30多年才用于临床
，我们进展这种SRS显微镜尽早利用于医院
。”起源：科技日报 常丽君

【点评】
　　该项技术将会极大的推进生理生化尤其是新陈代谢的钻研
，如能成熟地使用于人体
，对于人体生理学及医学钻研将有巨大的援手
。

【原文摘录】 Science Vol. 330 no. 6009 pp. 1368-1370 DOI: 10.1126/science.1197236
Video-Rate Molecular Imaging in Vivo with Stimulated Raman Scattering
Brian G. Saar1,Christian W. Freudiger, Jay Reichman, et al.
Optical imaging in vivo with molecular specificity is important in biomedicine because of its high spatial resolution and sensitivity compared with magnetic resonance imaging. Stimulated Raman scattering (SRS) microscopy allows highly sensitive optical imaging based on vibrational spectroscopy without adding toxic or perturbative labels. However, SRS imaging in living animals and humans has not been feasible because light cannot be collected through thick tissues, and motion-blur arises from slow imaging based on backscattered light. In this work, we enable in vivo SRS imaging by substantially enhancing the collection of the backscattered signal and increasing the imaging speed by three orders of magnitude to video rate. This approach allows label-free in vivo imaging of water, lipid, and protein in skin and mapping of penetration pathways of topically applied drugs in mice and humans.

4.  果蝇激活生殖细胞遗传基因来产生肿瘤
【提要】  
　　巴塞罗那的 科学家近日在Science上报路他们发现了果蝇幼虫利用生殖细胞的遗传法式来催生脑部肿瘤
。关关涉及到的有关基因就会维持健全的大脑
，这是初次发现关关这些有关基因能够使果蝇脑部肿瘤隐没
。注明这些生殖细胞的遗传基因对于此类肿瘤的发生有关键作用
。此前十年堆集的数据显示某些肿瘤如玄色素瘤和某些类癌的癌细胞会激活生殖细胞的遗传基因
。

【点评】
　　这项钻研注明癌基因并不愿定是癌症发生的原因
，生殖基因的激活也可能引发癌症
；蚣せ畹纳淼骺厥欠裾Ｊ呛苤匾
。

【原文摘录】 Science, December 23, 2010 DOI: 10.1126/science.1195481
Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila.
Janic A, Mendizabal L, Llamazares S, Rossell D, Gonzalez C.
Model organisms such as the fruit fly Drosophila melanogaster can help to elucidate the molecular basis of complex diseases such as cancer. Mutations in the Drosophila gene lethal (3) malignant brain tumor cause malignant growth in the larval brain. Here we show that l(3)mbt tumors exhibited a soma-to-germline transformation through the ectopic expression of genes normally required for germline stemness, fitness, or longevity. Orthologs of some of these genes were also expressed in human somatic tumors. In addition, inactivation of any of the germline genes nanos, vasa, piwi, or aubergine suppressed l(3)mbt malignant growth. Our results demonstrate that germline traits are necessary for tumor growth in this Drosophila model and suggest that inactivation of germline genes might have tumor-suppressing effects in other species.

5.  癌细胞自我覆灭与自我；さ男藕欧肿
【提要】
　　斯坦福大学医学院的钻研人员发现很多癌细胞自身带有自我覆灭的种子--细胞表表一种名为钙网素的蛋白—能召集循环系统的巨噬细胞来吞食消化他们
。而绝大无数癌细胞没有被覆灭是由于他们同时表白另一种信号蛋白CD47匹敌钙网素的作用
。

【点评】
　　CD47与钙网素的作用及二者平衡的调节会推进癌症免疫疗法的发展
。

【原文摘录】 Sci Transl Med 22 December 2010: Vol. 2, Issue 63, p. 63ra94
Calreticulin Is the Dominant Pro-Phagocytic Signal on Multiple Human Cancers and Is Counterbalanced by CD47
M. P. Chao, S. Jaiswal, R. Weissman-Tsukamoto, et al.
Under normal physiological conditions, cellular homeostasis is partly regulated by a balance of pro- and anti-phagocytic signals. CD47, which prevents cancer cell phagocytosis by the innate immune system, is highly expressed on several human cancers including acute myeloid leukemia, non-Hodgkin’s lymphoma, and bladder cancer. Blocking CD47 with a monoclonal antibody results in phagocytosis of cancer cells and leads to in vivo tumor elimination, yet normal cells remain mostly unaffected. Thus, we postulated that cancer cells must also display a potent pro-phagocytic signal. Here, we identified calreticulin as a pro-phagocytic signal that was highly expressed on the surface of several human cancers, but was minimally expressed on most normal cells. Increased CD47 expression correlated with high amounts of calreticulin on cancer cells and was necessary for protection from calreticulin-mediated phagocytosis. Blocking the interaction of target cell calreticulin with its receptor, low-density lipoprotein receptor–related protein, on phagocytic cells prevented anti-CD47 antibody–mediated phagocytosis. Furthermore, increased calreticulin expression was an adverse prognostic factor in diverse tumors including neuroblastoma, bladder cancer, and non-Hodgkin’s lymphoma. These findings identify calreticulin as the dominant pro-phagocytic signal on several human cancers, provide an explanation for the selective targeting of tumor cells by anti-CD47 antibody, and highlight the balance between pro- and anti-phagocytic signals in the immune evasion of cancer.

6. 微幼RNA表白模式的整体图谱分辨干细胞类别
【提要】
　　干细胞生物学在全世界引发人们对其能够最终建复身段部位的巨大进展
。只管好多科学家以为这是可行的
，但是必须克服好多阻碍
，蕴含令人忧郁的在建复器官时引发癌症的潜在风险
。而近日报路的加州大学的一项关于多能性干细胞的微幼RNA表白模式的钻研或许对此有所援手
。他们分析好多种多能性干细胞的微幼RNA表白模式
，发现所有的多能性干细胞微幼RNA表白模式并不一样
，但不是因细胞起源而异
，而是拥有分歧的p53 系统状态
。微幼RNA表白模式的整体图谱可能通知你这是何种细胞
，何种癌症
，是否干细胞等信息
。

【点评】
　　微幼RNA表白模式的整体图谱钻研也许会有助于钻研人体潜能再生细胞的定位和属性
。

【原文摘录】 Cell Stem Cell, Volume 7, Issue 6, 671-681, 3 December 2010
MicroRNA Profiling Reveals Two Distinct p53-Related Human Pluripotent Stem Cell States
Pierre Neveu, Min Jeong Kye, Shuping Qi, et al.
Highlights
miRNA profiles distinguish two categories of human pluripotent stem cells
The p53 network status distinguishes pluripotent cells independently of their origin
p53-targeting miRNAs change the classification status of iPSCs
A 2D representation of miRNA profiles tracks differentiation and reprogramming
Summary
Reprogramming methodologies have provided multiple routes for achieving pluripotency. However, pluripotency is generally considered to be an almost singular state, with subtle differences described between induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs). We profiled miRNA expression levels across 49 human cell lines, including ESCs, iPSCs, differentiated cells, and cancer cell lines. We found that the resulting miRNA profiles divided the iPSCs and hESCs examined into two distinct categories irrespective of the cell line origin. The miRNAs that defined these two pluripotency categories also distinguished cancer cells from differentiated cells. Transcriptome analysis suggested that several gene sets related to p53 distinguished these categories, and overexpression of the p53-targeting miRNAs miR-92 and miR-141 in iPSCs was sufficient to change their classification status. Thus, our results suggest a subdivision of pluripotent stem cell states that is independent of their origin but related to p53 network status.

7. 2010再生科学年度进展
　　凭据与人体再生复原科学的有关水平
，今年度登载的以下动态作为2010再生科学年度进展：

1.人体多能干细胞体表定向分化形成肠组织；
2.老鼠尝试批注建复端Ｄ芄荒孀ダ；
3.蝾螈更生肢体和器官的怪异酶；
4.成长因子TGF-β2和BMP4可使成熟细胞转化为成人干细胞；
5.性命复杂性的产生可能必须吓仔线粒体出现；
6.黄芩汤可减轻肠癌患者化疗危险；
7.细胞成长调控依附细胞质核传输；
8.洞螈长命钻研或解开衰老之谜；
9.脂肪可用作细胞内涵pH感触器；
10.发现上皮组织中神秘免疫细胞的职能和机理；
11.细胞归巢法使兔滑膜关节面再生；
12.节造细胞分化的力学成分；
13.关键基因节造哺乳动物组织再生；
14.细胞活动的集体调控节造胚胎的成长；
15.初次发现可发育成卵的干细胞;
16.精子形成过程中的细胞在一按时期内能够变回干细胞；
17.“活体生物反映器”“原位”造就再生新器官；
18.发现斑马鱼造血干细胞天活力理
。