The study of human cortical development has major implications for brain evolution and diseases but has remained elusive due to paucity of experimental models. Here we found that human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), cultured without added morphogens, recapitulate corticogenesis leading to the sequential generation of functional pyramidal neurons of all six layer identities. After transplantation into mouse neonatal brain, human ESC-derived cortical neurons integrated robustly and established specific axonal projections and dendritic patterns corresponding to native cortical neurons. The differentiation and connectivity of the transplanted human cortical neurons complexified progressively over several months in vivo, culminating in the establishment of functional synapses with the host circuitry. 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 modeling of human cortex diseases and brain repair

Pyramidal Neurons Derived from Human Pluripotent Stem Cells Integrate Efficiently into Mouse Brain Circuits In Vivo / Espuny-Camacho, I.; Michelsen, K. A.; Gall, D.; Linaro, D.; Hasche, A.; Bonnefont, J.; Bali, C.; Ordu, z D.; Bilheu, A.; Herpoel, A.; Lambert, N.; Gaspard, N.; Peron, S.; Schiffmann, S. N.; Giugliano, M.; Gaillard, A.; Vanderhaeghen, P.. - In: NEURON. - ISSN 1097-4199. - 77:3(2013), pp. 440-456. [10.1016/j.neuron.2012.12.011]

Pyramidal Neurons Derived from Human Pluripotent Stem Cells Integrate Efficiently into Mouse Brain Circuits In Vivo

Giugliano, M.;
2013-01-01

Abstract

The study of human cortical development has major implications for brain evolution and diseases but has remained elusive due to paucity of experimental models. Here we found that human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), cultured without added morphogens, recapitulate corticogenesis leading to the sequential generation of functional pyramidal neurons of all six layer identities. After transplantation into mouse neonatal brain, human ESC-derived cortical neurons integrated robustly and established specific axonal projections and dendritic patterns corresponding to native cortical neurons. The differentiation and connectivity of the transplanted human cortical neurons complexified progressively over several months in vivo, culminating in the establishment of functional synapses with the host circuitry. 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 modeling of human cortex diseases and brain repair
2013
77
3
440
456
https://doi.org/10.1016/j.neuron.2012.12.011
Espuny-Camacho, I.; Michelsen, K. A.; Gall, D.; Linaro, D.; Hasche, A.; Bonnefont, J.; Bali, C.; Ordu, z D.; Bilheu, A.; Herpoel, A.; Lambert, N.; Gas...espandi
File in questo prodotto:
File Dimensione Formato  
PIIS089662731201121X.pdf

non disponibili

Descrizione: Articolo principale
Tipologia: Versione Editoriale (PDF)
Licenza: Non specificato
Dimensione 4.96 MB
Formato Adobe PDF
4.96 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/99664
Citazioni
  • ???jsp.display-item.citation.pmc??? 244
  • Scopus 425
  • ???jsp.display-item.citation.isi??? 396
social impact