Feb 26, 2016

Autonomous Extracellular Matrix Remodeling Controls a Progressive Adaptation in Muscle Stem Cell Regenerative Capacity during Development

Cell Reports
Matthew Timothy TierneyAlessandra Sacco

Abstract

Muscle stem cells (MuSCs) exhibit distinct behavior during successive phases of developmental myogenesis. However, how their transition to adulthood is regulated is poorly understood. Here, we show that fetal MuSCs resist progenitor specification and exhibit altered division dynamics, intrinsic features that are progressively lost postnatally. After transplantation, fetal MuSCs expand more efficiently and contribute to muscle repair. Conversely, niche colonization efficiency increases in adulthood, indicating a balance between muscle growth and stem cell pool repopulation. Gene expression profiling identified several extracellular matrix (ECM) molecules preferentially expressed in fetal MuSCs, including tenascin-C, fibronectin, and collagen VI. Loss-of-function experiments confirmed their essential and stage-specific role in regulating MuSC function. Finally, fetal-derived paracrine factors were able to enhance adult MuSC regenerative potential. Together, these findings demonstrate that MuSCs change the way in which they remodel their microenvironment to direct stem cell behavior and support the unique demands of muscle development or repair.

  • References49
  • Citations15

References

  • References49
  • Citations15

Citations

Mentioned in this Paper

Microarray Analysis
Fetal Structures
Myogenesis
Procollagen Type VI
Regulation of Biological Process
Cell Division
Extracellular Matrix
Stem Cell Transplant
Tenascin
Soleus Muscle Structure

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