Asymmetric Division in Muscle Stem Cells

Christian Elabd, Ph.D.Joey Pham, B.A.

- The muscle system is a model for quiescence (resting) and activity

- Satellite cells, or muscle stem cells, can regenerate repeatedly

- Satellite cells give rise to myoblasts (mostly), and fibroblasts, adipocytes, chondrocytes.

intactmuscle

intactmuscle

injuredmuscle

regeneratedmuscle

Histology 2 weeks after injury Hematoxylin and eosin cross section

satellitecells

myonuclei

myofiber

Pictures from MJ Conboy, UC Berkeley

Muscle System

Muscle Regeneration

Resting muscle Fiber

Quiescent Muscle

Stem Cell

1) ActivationMyotrauma

2) Proliferation

3) Regeneration

Fusion to repair damaged muscle fibers

Fusion to produce new muscle fibers

Multi-nucleationSelf

RenewalReturn to resting state

Symmetry Asymmetry

Stem

Stem

Diff

Stem

Stem

Asymmetric Division = Segregation of DNA, RNA or Proteins in one daughter cell

self renewal differentiation

Symmetric versus Asymmetric Division

Satellite

Satellite Satellite=

=

Myoblast

Satellite Dividing Satellite

Option 1

Option 2

=Option 3

Myoblast Myoblast

+

+

+

Symmetric versus Asymmetric Division

in the Context of Muscle

Hoechst Sca-1Desmin Merge

Differentiated cells are Desmin positive. Non-differentiated cells are Sca-1 positive.

Conboy MJ et al. PLoS Biol. 2007 Jul;5(7):e182

Asymmetric Division in the Context of Muscle

Summary of Asymmetric DivisionHoechst

Sca-1

Desmin

Merge

While most cells in the body divide strictly symmetrically, stem cells have the ability to divide asymmetrically as well.

In the context of muscle regeneration, asymmetric division may allow for muscle regeneration without exhausting the pool of satellite cells (or muscle stem cells).

Understanding the mechanism of asymmetric division is essential to advancing the control of stem cell self-renewal versus differentiation. Such control is necessary for the use of stem cells in regenerative medicine.