Other factors have also been found that regulate cell size. One example is the transcription factor myostatin, a negative regulator of skeletal muscle size that inhibits muscle cell differentiation. Myostatin inhibits activation of the Akt/mTOR/p70S6 protein synthesis pathway, which mediates both differentiation in myoblasts and hypertrophy in myotubes [69]. Ion channel activity has been shown to simultaneously affect cell cycle and cell volume in the S phase of the cell cycle in embryonic stem cells [70]. Also, the Erg channel is critical in controlling cell volume during cell cycle in embryonic stem cells. In support of this, cell death following Erg inhibition is a consequence of the inability to regulate cell volume [71]. The Notch pathway has been studied in relationship to cell size. Recently, type II neural stem cells in Drosophila are used for studying CSC-initiated tumorigenesis [72]. These cells, marked by a transcriptional target of Notch involved in their self-renewal and the absence of a differentiation-promoting transcription factor, give rise to immature progenitors that are small in size. Notch signaling is required for the maintenance of these normal stem cells although the specific mechanisms are unclear. When Notch signaling is inhibited, these neural stem cells exhibit reduced cell growth and cell size [72]. Finally, ectopic expression of the p21 cyclin-dependent kinase inhibitor has been shown to induce hypertrophy, increase cell size and reduce the replicative lifespan of cells [73].