Smad4 Restricts Differentiation to Promote Expansion of Satellite Cell Derived Progenitors During Skeletal Muscle Regeneration

Overview

Journal Elife

Specialty Biology

Date 2016 Nov 19

PMID 27855784

Citations 19

Authors

Nicole D Paris

Andrew Soroka

Alanna Klose

Wenxuan Liu

Joe V Chakkalakal

Affiliations

Soon will be listed here.

Abstract

Skeletal muscle regenerative potential declines with age, in part due to deficiencies in resident stem cells (satellite cells, SCs) and derived myogenic progenitors (MPs); however, the factors responsible for this decline remain obscure. TGFβ superfamily signaling is an inhibitor of myogenic differentiation, with elevated activity in aged skeletal muscle. Surprisingly, we find reduced expression of , the downstream cofactor for canonical TGFβ superfamily signaling, and the target in aged SCs and MPs during regeneration. Specific deletion of Smad4 in adult mouse SCs led to increased propensity for terminal myogenic commitment connected to impaired proliferative potential. Furthermore, SC-specific Smad4 disruption compromised adult skeletal muscle regeneration. Finally, loss of Smad4 in aged SCs did not promote aged skeletal muscle regeneration. Therefore, SC-specific reduction of Smad4 is a feature of aged regenerating skeletal muscle and Smad4 is a critical regulator of SC and MP amplification during skeletal muscle regeneration.

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