NFAT and the regulation of Sca-1 in muscle cells

描述（由申请人提供）： 肌肉前体细胞（MPC）是肌肉生长和再生所必需的。Sca-1对MPC的生长和分化具有负调控作用。初步数据表明Sca-1受NFAT家族转录因子调控。该提案的目标是进一步研究和确定NFAT在Sca-1调节中的作用。将使用缺乏或过表达肌肉中表达的NFAT蛋白（NFATc 1-c3）的细胞来检查特定NFAT同种型在Sca-1活化中的作用。为了确定NFAT是否直接激活Sca-1表达，将研究NFAT结合Sca-1启动子的能力;还将确定NFAT调节所必需和足够的Sca-1启动子区域。将研究参与肌肉生长和修复的生长因子对Sca-1表达的激活，并确定对NFAT的依赖性。这些研究可能会导致开发新的方法来操纵疾病，再生和衰老中的肌源性干细胞，以及定义新的治疗靶点来促进肌肉生长。

DESCRIPTION (provided by applicant): Muscle precursor cells (MPC) are essential for muscle growth and regeneration. Sca-1 has been proposed to negatively regulate growth and differentiation of MPC. Preliminary data suggest that Sca-1 is regulated by the NFAT family of transcription factors. The goal of this proposal is to further investigate and define the role of NFAT in Sca-1 regulation. The role of specific NFAT isoforms in Sca-1 activation will be examined using cells lacking or overexpressing NFAT proteins expressed in muscle (NFATc1-c3). To determine if NFAT directly activates Sca-1 expression, the ability of NFAT to bind the Sca-1 promoter will be investigated; the regions of the Sca-1 promoter necessary and sufficient for regulation by NFAT will also be determined. Activation of Sca-1 expression by growth factors involved in muscle growth and repair will be studied, and dependence on NFAT determined. These studies may result in the development of new methods for manipulating myogenic stem cells in disease, regeneration, and aging, as well as define new therapeutic targets for enhancing muscle growth.