Figure 6 | Cell Death & Disease

Figure 6

From: Notch signaling regulates myogenic regenerative capacity of murine and human mesoangioblasts

Figure 6

Hypothetical models of Notch-based tuning of MAB myogenic differentiation. (a) The intrinsic difference in the levels of Dll1-triggered Notch1 activation and of Mef2C could explain, at least partially, the difference in spontaneous myogenic capability between murine and human MABs in our experimental system. According to this hypothesis, murine MABs present low levels of Dll1-triggered signaling and of Mef2C during the commitment stage. At a later step of differentiation, once NICD is removed from the complex, Mef2C activity levels are therefore minimal. Human MABs present intrinsically higher levels of DLL1 and MEF2C in vitro. As a consequence, murine MABs fail to spontaneously produce mature myocytes in vitro, whereas human MABs differentiate, although with low efficiency, spontaneously. Transient overexpression of Dll1/DLL1 and Mef2C/MEF2C during the commitment stage induces complete recruitment of Mef2C/MEF2C and Maml1/MAML1 by NICD, thereby reinforcing Mef2C activity and myogenic capability of both murine and human MABs, as observed in vivo. (b) Representative scheme of the hypothetical model regarding Dll1 involvement during the commitment-differentiation transition of MABs in vivo, according to our experimental setup with transgenic MABs and muscles. Dll1-Notch1 interactions between the dystrophic fiber and the homing MABs trigger their commitment and engraftment, plausibly through Maml1/Mef2C interplay. After engraftment, the signaling is discontinued, NICD removed and the engrafted MABs activate the myogenic program, likely through sustained levels of Mef2C activity

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