Delta-Like 4 Activates Notch 3 to Regulate Self-Renewal in Skeletal Muscle Stem Cells. / Low, Siew Hui; Barnes, Josephine; Zammit, Peter ; Beauchamp, Jonathan.
In: Stem Cells, Vol. 36, No. 3, 03.2018, p. 458-466.Research output: Contribution to journal › Article › peer-review
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Delta-Like 4 Activates Notch 3 to Regulate Self-Renewal in Skeletal Muscle Stem Cells. / Low, Siew Hui; Barnes, Josephine; Zammit, Peter ; Beauchamp, Jonathan.
In: Stem Cells, Vol. 36, No. 3, 03.2018, p. 458-466.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Delta-Like 4 Activates Notch 3 to Regulate Self-Renewal in Skeletal Muscle Stem Cells
AU - Low, Siew Hui
AU - Barnes, Josephine
AU - Zammit, Peter
AU - Beauchamp, Jonathan
PY - 2018/3
Y1 - 2018/3
N2 - Notch signaling is essential to maintain skeletal muscle stem cells in quiescence. However, the precise roles of different Notch receptors are incompletely defined. Here, we demonstrate a role for Notch3 (N3) in the self-renewal of muscle stem cells. We found that N3 is active in quiescent C2C12 reserve cells (RCs), and N3 over-expression and knockdown studies in C2C12 and primary satellite cells reveal a role in self-renewal. The Notch ligand Delta-like 4 (Dll4) is expressed by newly formed myotubes and interaction with this ligand is sufficient to maintain N3 activity in quiescent C2C12 RCs to prevent activation and progression into the cell cycle. Thus, our data suggest a model whereby during regeneration, expression of Dll4 by nascent muscle fibers triggers N3 signaling in associated muscle stem cells to recruit them to quiescence, thereby renewing the stem cell pool.
AB - Notch signaling is essential to maintain skeletal muscle stem cells in quiescence. However, the precise roles of different Notch receptors are incompletely defined. Here, we demonstrate a role for Notch3 (N3) in the self-renewal of muscle stem cells. We found that N3 is active in quiescent C2C12 reserve cells (RCs), and N3 over-expression and knockdown studies in C2C12 and primary satellite cells reveal a role in self-renewal. The Notch ligand Delta-like 4 (Dll4) is expressed by newly formed myotubes and interaction with this ligand is sufficient to maintain N3 activity in quiescent C2C12 RCs to prevent activation and progression into the cell cycle. Thus, our data suggest a model whereby during regeneration, expression of Dll4 by nascent muscle fibers triggers N3 signaling in associated muscle stem cells to recruit them to quiescence, thereby renewing the stem cell pool.
U2 - 10.1002/stem.2757
DO - 10.1002/stem.2757
M3 - Article
VL - 36
SP - 458
EP - 466
JO - Stem Cells
JF - Stem Cells
SN - 1549-4918
IS - 3
ER -