Cloned Myogenic Cells Can Transdifferentiate In Vivo into Neuron-Like Cells

Background: The question of whether intact somatic cells committed to a specific differentiation fate, can be reprogrammed in vivo by exposing them to a different host microenvironment is a matter of controversy. Many reports on transdifferentiation could be explained by fusion with host cells or reflect intrinsic heterogeneity of the donor cell population. Methodology/Principal Findings: We have tested the capacity of cloned populations of mouse and human muscle progenitor cells, committed to the myogenic pathway, to transdifferentiate to neurons, following their inoculation into the developing brain of newborn mice. Both cell types migrated into various brain regions, and a fraction of them gained a neuronal morphology and expressed neuronal or glial markers. Likewise, inoculated cloned human myogenic cells expressed a human specific neurofilament protein. Brain injected donor cells that expressed a YFP transgene controlled by a neuronal specific promoter, were isolated by FACS. The isolated cells had a wild-type diploid DNA content. Conclusions: These and other results indicate a genuine transdifferentiation phenomenon induced by the host brain microenvironment and not by fusion with host cells. The results may potentially be relevant to the prospect of autologous cell therapy approach for CNS diseases

Altered presynaptic ultrastructure in excitatory hippocampal synapses of mice lacking dystrophins Dp427 or Dp71.

International audienceMental retardation is a feature of X-linked Duchenne muscular dystrophy (DMD) which likely results from the loss of the brain full-length (Dp427) and short C-terminal products of the dystrophin gene, such as Dp71. The loss of Dp427 or Dp71 is known to alter hippocampal glutamate-dependent synaptic transmission and plasticity in mice. Although dystrophins have a selective postsynaptic expression in brain, a putative role in retrograde regulation of transmitter release was suggested by studies in Drosophila. Here we used electron microscopy to analyze the distribution of synaptic vesicles in CA1 hippocampal axospinous non perforated-excitatory synapses of mice lacking Dp427 or Dp71 compared to control littermates. We found that the density of morphologically-docked vesicles is increased and the vesicle size is reduced in mice lacking Dp427, while in Dp71-null mice there is a decrease in the density of vesicles located in the vicinity of the active zone and an increase in the vesicle size and in the width of synaptic clefts. This is the first indication that the loss of mammalian brain dystrophins impacts on the presynaptic ultrastructural organization of central glutamatergic synapses, which may explain some of the alterations of synapse function and plasticity that contribute to intellectual disability in DMD

Increased efficiency of homologous recombination in ES cells by cleavage at both ends of homology in the targeting vector.

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