Generation of functional human neurons from reprogrammed skin cells
06/02/2013

In a study published in Neuron, researchers lead by Pierre Vanderhaeghen, WELBIO investigator at the IRIBHM, Université Libre de Bruxelles, and ULB Neuroscience Institute (UNI), Belgium, in collaboration with laboratories of Afsaneh Gaillard (INSERM/U. Poitiers), Serge Schiffmann (ULB) and Michele Giugliano (U. Antwerpen), open new perspectives on the study of the human cortex, by describing for the first time the generation of cortical neurons from human pluripotent stem cells, followed by their highly successful transplantation in the mouse brain.

As explained by Dr. Vanderhaeghen in a video, the cerebral cortex is the most complex structure in our brain, and the major center of most higher cognitive functions. Cortical nerve cells, or neurons, are thus essential for proper function of the human brain, and many neurological and neuropsychiatric diseases strike the cerebral cortex. A major challenge to understand the human cerebral cortex function and its diseases is the difficulty to study it experimentally.

The same team had previously described the generation of cortical cells from mouse embryonic stem cells (Gaspard et al. Nature 2008) but it had remained unclear whether it was possible to generate transplantable and functional cortical neurons from human pluripotent stem cells.

Here the scientists developed an efficient method that drives the generation of cortical neurons from human pluripotent stem cells, whether derived from the embryo or induced by reprogramming of skin cells from adult donors. The system recapitulates in a dish the key events that normally take place during normal development in the embryonic brain in utero, thereby leading to the generation of a complex repertoire of functional cortical neurons (Figure to the left).

Most importantly, the scientists then tested the potential and function of the human neurons by transplanting them into the mouse neonatal brain. Remarkably, they found that the transplanted human neurons integrated robustly and could even connect functionally with the circuits of the host cortex (Figure to the right).

130206 Espuny Camacho Fig 2The team of Dr. Vanderhaeghen thus generated a model of human cortex development and function, in the dish and in a whole organism, that constitutes an innovative tool to study human brain function and diseases.

These findings have important implications for basic and clinical neurosciences. Indeed, this model of human corticogenesis provides novel ways to study the human-specific mechanisms underlying the generation of cortical cells, and thereby understand the links between the development and evolution of the human brain. In a clinical perspective, it offers the possibility to study experimentally human cortical neurons bearing specific diseases (such as genetic forms of epilepsy, autism, neurodegeneration) in the physiological context of the whole brain, thus mimicking as closely as possible the complexity of certain human brain diseases. This may lead to unique ways to a better understanding of several brain diseases and design of treatments.

Espuny-Camacho et al. Pyramidal Neurons Derived from Human Pluripotent Stem Cells Integrate Efficiently into Mouse Brain Circuits In Vivo. Neuron (2013) 77: 440-456


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