干细胞重大新发现：库存分子开关

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干细胞重大新发现：库存分子开关 受伤后，甚至是成熟肌肉都能因为肌肉干细胞储备而很好地恢复。这种细胞被称为卫星细胞，它能用于修复。到目前为止，人们还不清楚这种卫星细胞和肌肉前体细胞的供应的机理已经卫星细胞如何发育和保持“新鲜”。
  受伤后，甚至是成熟肌肉都能因为肌肉干细胞储备而很好地恢复。这种细胞被称为卫星细胞，它能用于修复。到目前为止，人们还不清楚这种卫星细胞和肌肉前体细胞的供应的机理已经卫星细胞如何发育和保持“新鲜”。

  德国柏林Max Delbrück分子医学中心的发育生物学教授Carmen Birchmeier、Elena Vasyutina博士等人现在证实一种叫做RBP-J的分子开关能够调节这个“青春之泉”。如果没有了这个开关，卫星细胞就会不收控制地形成肌肉细胞，从而导致卫星细胞库的耗尽。其结果是一个生物和胚胎的发育阶段的肌肉形成太少。

  这项研究的结果刊登在近日的《PNAS》的网络版上，这项研究对干细胞治疗将来的发展具有重要意义。

  肌肉干细胞是在二十世纪六十年代初期发现的。在很长的一段时间里，研究人员只能在电子显微镜的帮助下鉴定它们。这些细胞定位在肌肉膜和周围层。已经知道有时，卫星细胞具有特殊的表面分子和转录因子，从而使研究人员能够更容易发现他们。

  RBP-J开关与一个对细胞交流至关重要的信号途径Notch信号途径有关，并且还是信号的一个关键介导因子。这个信号途径在活体生物和胚胎中生物体的发育都很关键。

  研究人员证实卫星细胞和肌肉前体细胞保持着它们的干细胞特征，这是因为RBP-J使它们维持在早期发育阶段——这些发现显示出这种分子开关对干细胞治疗具有特殊意义。

  其他一些研究组之前证实当卫星细胞注射到小鼠的肌肉中时能促进肌肉的再生。而且，由于这种作用，肌肉还能重新补充它们的卫星细胞库存。研究人员推测影响RBP-J蒋能够促进以卫星细胞为基础的干细胞疗法。

部分英文原文：

PNAS | March 13, 2007 | vol. 104 | no. 11 | 4443-4448


RBP-J (Rbpsuh) is essential to maintain muscle progenitor cells and to generate satellite cells

Elena Vasyutina*, Diana C. Lenhard*, Hagen Wende*, Bettina Erdmann*, Jonathan A. Epstein, and Carmen Birchmeier*,

*Max Delbrück Center for Molecular Medicine, Robert R鰏sle Strasse 10, 13125 Berlin, Germany; and Department of Cell and Developmental Biology and the Cardiovascular Institute, University of Pennsylvania, 954 BRB II, 421 Curie Boulevard, Philadelphia, PA 19104

Edited by Eric N. Olson, University of Texas Southwestern Medical Center, Dallas, TX, and approved January 22, 2007 (received for review December 1, 2006)


In the developing muscle, a pool of myogenic progenitor cells is formed and maintained. These resident progenitors provide a source of cells for muscle growth in development and generate satellite cells in the perinatal period. By the use of conditional mutagenesis in mice, we demonstrate here that the major mediator of Notch signaling, the transcription factor RBP-J, is essential to maintain this pool of progenitor cells in an undifferentiated state. In the absence of RBP-J, these cells undergo uncontrolled myogenic differentiation, leading to a depletion of the progenitor pool. This results in a lack of muscle growth in development and severe muscle hypotrophy. In addition, satellite cells are not formed late in fetal development in conditional RBP-J mutant mice. We conclude that RBP-J is required in the developing muscle to set aside proliferating progenitors and satellite cells.


muscle differentiation | myogenic progenitors | Notch signaling

Freely available online through the PNAS open access option.

Author contributions: E.V. and D.C.L. contributed equally to this work; C.B. designed research; E.V., D.C.L., and B.E. performed research; H.W. and J.A.E. contributed new reagents/analytic tools; E.V., D.C.L., B.E., and C.B. analyzed data; and C.B. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS direct submission.

This article contains supporting information online at www.pnas.org/cgi/content/full/0610647104/DC1.

To whom correspondence should be addressed. E-mail: cbirch@mdc-berlin.de

英文全文链接：http://www.pnas.org/cgi/content/full/104/11/4443?