范辰铭最新《Nature》干细胞成果

【字体: 时间:2009年06月30日 来源:生物通

编辑推荐:

  生物通报道,华盛顿卡耐基研究所胚胎发育系,Johns Hopkins大学生物系,印第安大大学医学院的研究人员在最新的Nature在线版上发布干细胞研究新成果Adult satellite cells and embryonic muscle progenitors have distinct genetic requirements。

  

生物通报道,华盛顿卡耐基研究所胚胎发育系,Johns Hopkins大学生物系,印第安大大学医学院的研究人员在最新的Nature在线版上发布干细胞研究新成果Adult satellite cells and embryonic muscle progenitors have distinct genetic requirements

 

文章通讯作者是卡耐基研究所的范辰铭教授(chen-ming Fan)和印第安大大学医学院的Simon J.Conway教授。

 

干细胞分成体干细胞(Adult Stem Cell)和胚胎干细胞(Embryonic Stem Cell)两种,两者的细胞特征和分化潜能都具有差异,当然,两种干细胞在发育过程中起调控作用的基因也各不相同。

 

本研究主要以哺乳动物的肌细胞为研究模型,在胚胎发育前期,哺乳动物肌细胞的祖细胞其生肌潜能,存活能力,迁移能力等都依赖于Pax3Pax7,但是围产期间,仅Pax7对祖细胞的发育起关键调控作用。

 

在目前的研究中,对Pax7的调节功能的研究已经受几个体外实验数据支持,但是缺乏活体实验的验证。

 

在本篇研究中,研究小组以小鼠模型证实了这一观点。并且证实成体肌肉干细胞不受Pax3Pax7的调控,当研究小组将两基因失活后,成年小鼠的肌肉再生不受影响。

 

这些干细胞发育基因调控差异的发现有助科学家更深入了解干细胞的发育,尤其对将来干细胞临床移植具有指导性意义。

(生物通 小茜)

范辰铭简介

 

求学经历

B.S.

National University of Taiwan

Ph.D.

Harvard University

Postdoctoral

University of California, San Francisco

 

研究课题简介

Our Lab uses the mouse as a model system to study the genes and the cellular mechanisms that orchestrate early developmental processes in the mammal. Two primary areas of interest are the musculoskeletal system and the neuroendocrine system.

 

生物通推荐原文检索:

Adult satellite cells and embryonic muscle progenitors have distinct genetic requirementsnear-final version

Christoph Lepper1,2, Simon J. Conway3 & Chen-Ming Fan1

 

Department of Embryology, Carnegie Institution, 3520 San Martin Drive, Baltimore, Maryland 21218, USA

Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA

Riley Heart Research Center, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA

 

Abstract

Myogenic potential, survival and expansion of mammalian muscle progenitors depend on the myogenic determinants Pax3 and Pax7 embryonically1, and Pax7 alone perinatally2, 3, 4, 5. Several in vitro studies support the critical role of Pax7 in these functions of adult muscle stem cells5, 6, 7, 8 (satellite cells), but a formal demonstration has been lacking in vivo. Here we show, through the application of inducible Cre/loxP lineage tracing9 and conditional gene inactivation to the tibialis anterior muscle regeneration paradigm, that, unexpectedly, when Pax7 is inactivated in adult mice, mutant satellite cells are not compromised in muscle regeneration, they can proliferate and reoccupy the sublaminal satellite niche, and they are able to support further regenerative processes. Dual adult inactivation of Pax3 and Pax7 also results in normal muscle regeneration. Multiple time points of gene inactivation reveal that Pax7 is only required up to the juvenile period when progenitor cells make the transition into quiescence. Furthermore, we demonstrate a cell-intrinsic difference between neonatal progenitor and adult satellite cells in their Pax7-dependency. Our finding of an age-dependent change in the genetic requirement for muscle stem cells cautions against inferring adult stem-cell biology from embryonic studies, and has direct implications for the use of stem cells from hosts of different ages in transplantation-based therapy.

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