Ascl2 as a novel regulator of satellite cells

Min Wang, Purdue University

Abstract

The skeletal muscle is the most abundant tissue in humans and its malfunction affects life quality. Heritable muscle diseases (including various forms of congenital and degenerative muscular dystrophy) and physiological muscle wasting conditions such as disuse and aging associated muscle atrophy represent two categories of common muscle disorders that affect billions of people worldwide. Satellite cells are myogenic stem cells that mediate postnatal muscle growth, maintenance and regeneration. Unfortunately, satellite cell functions are often misregulated under many disease settings. Thus, understanding the key factors and signaling pathways that critically regulate satellite cell function is fundamental to the development of stem cell-based therapies to combat degenerative muscle diseases and muscle wasting conditions. The transcription factor achaete-scute complex homolog 2 (Ascl2) has been shown as an important regulator of placenta development and intestinal stem cell homeostasis. In this study, we discovered a novel role of Ascl2 in muscle satellite cells. Ascl2 is not expressed in quiescent satellite cells but its expression is increased during proliferation and differentiation of myoblasts. Overexpression of Ascl2 robustly up-regulates the expression of two myogenic regulatory transcription factors, MyoD and myogenin, and promotes myogenic differentiation. In addition, we found that Ascl2 up-regulates the expression of several targets of the Notch signaling pathway, including Hes1 and HeyL. However, activation of Notch signaling conversely inhibits Ascl2 expression. Given the antimyogenic effect of Notch signaling and promyogenic action of Ascl2, it is concluded that Ascl2 interacts with the Notch signaling pathway to dynamically regulate myoblast proliferation and myogenic differentiation.

Degree

M.S.

Advisors

Kuang, Purdue University.

Subject Area

Molecular biology|Cellular biology|Developmental biology

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