美国研究人员宣布开发出了一种生物基因“开关”,该“开关”能让活体哺乳动物的肌肉干细胞内出现变异,从而帮助人们了解动物体内肌肉的再生机制。该项研究有望帮助科学家寻找到某种基因开关或药物,促使人体内生长新的肌肉细胞,取代那些因种种原因发生受损、衰弱或不工作的肌肉细胞。此项研究成果发表在《美国实验生物学学会联合会杂志》(FASEB J)网络版上。
研究人员是通过培育携带特殊基因“Cre”的实验鼠取得研究成果的。据介绍,“Cre”基因被激活时,能够触发肌肉干细胞内发生变异。这种“Cre”基因触发机理仅限于肌肉干细胞,且需要一种特殊的药物来激活。研究人员的工作分为两部分,一是利用荧光技术将干细胞和它们的衍生物进行可视化处理,以便准确地了解肌肉组织生成点;二是激活肌肉干细胞中导致癌症的变异,深入了解过去曾是难以琢磨的肌肉癌症的源头。
德克萨斯大学健康科学中心助理教授、高级研究员查理斯·凯勒表示,他们希望自己建立的基因工程实验鼠模型能够帮助科学家和临床医生更好地了解如何利用肌肉干细胞再生肌肉组织。对于自己从事的儿童肌肉癌症病研究,他表示实验鼠模型能让他们了解肿瘤是如何产生和发展的,同时希望能开发出比化疗副作用(毒性)小的肌肉癌症治疗方法。
美国实验生物学学会联合会杂志总编辑吉罗德·韦斯曼表示,在实验鼠上完成的研究不仅表明了在生命体中干细胞如何转化成肌肉,而且帮助人们进一步接近利用干细胞修复受伤肌肉或残体的未来。
据悉,2007年诺贝尔生理学或医学奖获得者马里奥·卡佩奇博士参与了此项研究。(生物谷Bioon.com)
生物谷推荐原始出处:
FASEB J,doi: 10.1096/fj.08-128116,Koichi Nishijo,Charles Keller
Biomarker system for studying muscle, stem cells, and cancer in vivo
Koichi Nishijo, Tohru Hosoyama, Christopher R. R. Bjornson, Beverly S. Schaffer, Suresh I. Prajapati, Ali N. Bahadur, Mark S. Hansen, Mary C. Blandford, Amanda T. McCleish, Brian P. Rubin, Jonathan A. Epstein, Thomas A. Rando, Mario R. Capecchi, and Charles Keller
Bioluminescent reporter genes are sensitive in situ tools for following disease progression in preclinical models, albeit they are subject to scattering and absorption in deep tissues. We have generated a bicistronic Cre/LoxP reporter mouse line that pairs the expression of firefly luciferase with quantifiable expression of a human placental alkaline phosphatase that is secreted into the serum (SeAP). With the use of this dual-modality bioreporter with a novel, inducible Pax7-CreER line for tracking muscle satellite cells, we demonstrate the longitudinal kinetics of muscle stem cell turnover, accounting for a doubling of the signal from satellite cell and progeny every 3.93 wk in the transition from adolescence to early adulthood. We also show that this dual-modality bioreporter can be incorporated in preclinical cancer models, whereby SeAP activity is reflective of tumor burden. Thus, this dual bioreporter permits both spatial localization and accurate quantification of biological processes in vivo even when the tissue of interest is deep within the animal.—Nishijo, K., Hosoyama, T., Bjornson, C. R. R., Schaffer, B. S., Prajapati, S. I., Bahadur, A. N., Hansen, M. S., Blandford, M. C., McCleish, A. T., Rubin, B. P., Epstein, J. A., Rando, T. A., Capecchi, M. R., Keller, C. Biomarker system for studying muscle, stem cells, and cancer in vivo.