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Pyramidal neurons derived from human pluripotent stem cells mature to form functional synapses in vitro and integrate e ciently into mouse brain circuits in vivo
Espuny Camacho, Ira Mercedes
2014
 

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Keywords :
model for corticogenesis in vitro; human embryonic stem cells; in vivo pattern of hESC-derived cortical neuron connectivity
Abstract :
[en] The generation of in vitro and in vivo models to study human cortical development is essential to address the molecular and cellular mechanisms involved in brain evolution as well as to elucidate major pathways affected in developmental and degenerative cortical diseases. Here we found that human embryonic (ESC) and induced pluripotent (iPSC) stem cells, cultured without added morphogens, recapitulate corticogenesis in vitro leading to the sequential generation of functional pyramidal neurons of all six layers identities. Following transplantation into the mouse neonatal brain, human ESC-derived cortical neurons integrated robustly and established specific axonal projections corresponding to native cortical neurons of diverse cortical layers and areas. Neuronal differentiation and connectivity complexified progressively over several months in vivo, culminating with the development of elaborate dendritic patterns, the presence of dendritic spines, and the establishment of reciprocal synapses with the host in a time dependent fashion highly reminiscent of the human species. Our data demonstrate that human cortical neurons generated in vitro from ESC/iPSC can develop complex hodological properties characteristic of the cerebral cortex in vivo, thereby offering unprecedented opportunities for the modelling of human cortex diseases, and brain repair. Please, state why this workshop is useful for you: My present research is focused on the modeling of human cortical development and the mechanisms altered in some of the diseases affecting the development or the aging cerebral cortex. My future career and work progress could profit from the study of different systems in vitro aiming to reproduce cortical organogenesis, as well as the study of the epigenetic programs determining fate determination in the embryo.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Espuny Camacho, Ira Mercedes  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Language :
English
Title :
Pyramidal neurons derived from human pluripotent stem cells mature to form functional synapses in vitro and integrate e ciently into mouse brain circuits in vivo
Publication date :
29 September 2014
Event name :
SYNERG of young scientists Munich Cluster for Systems Neurology
Event place :
Munich, Germany
Event date :
29-09-2014
Available on ORBi :
since 30 April 2021

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