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

被引：410

作者：

Espuny-Camacho, Ira ^{[1
,2
]}

Michelsen, Kimmo A. ^{[1
,2
]}

Gall, David ^{[3
,4
]}

Linaro, Daniele ^{[7
]}

Hasche, Anja ^{[1
,2
]}

Bonnefont, Jerome ^{[1
,2
]}

Bali, Camilia ^{[1
,2
]}

Orduz, David ^{[3
,4
]}

Bilheu, Angeline ^{[1
,2
]}

Herpoel, Adele ^{[1
,2
]}

Lambert, Nelle ^{[1
,2
,10
]}

Gaspard, Nicolas ^{[1
,2
]}

Peron, Sophie ^{[6
]}

Schiffmann, Serge N. ^{[3
,4
]}

Giugliano, Michele ^{[7
,8
,9
]}

Gaillard, Afsaneh ^{[6
]}

Vanderhaeghen, Pierre ^{[1
,2
,5
]}

机构：

[1] Univ Libre Brussels, Inst Rech Biol Humaine & Mol IRIBH, B-1070 Brussels, Belgium

[2] ULB Neurosci Inst, B-1070 Brussels, Belgium

[3] Univ Libre Brussels, Lab Neurophysiol, B-1070 Brussels, Belgium

[4] Univ Libre Brussels, UNI, B-1070 Brussels, Belgium

[5] Univ Libre Brussels, Welbio, B-1070 Brussels, Belgium

[6] Univ Poitiers, Expt & Clin Neurosci Lab, Cellular Therapies Brain Dis Grp, INSERM,U1084, F-86022 Poitiers, France

[7] Univ Antwerp, Dept Biomed Sci, Theoret Neurobiol & Neuroengn Lab, B-2610 Antwerp, Belgium

[8] Ecole Polytech Fed Lausanne, Swiss Fed Inst Technol, Brain Mind Inst, Lab Neural Microcircuitry, CH-1015 Lausanne, Switzerland

[9] Univ Sheffield, Dept Comp Sci, Sheffield S10 2TN, S Yorkshire, England

[10] Univ Libre Brussels, Dept Med Genet, Hop Erasme, B-1070 Brussels, Belgium

来源：

NEURON | 2013年 / 77卷 / 03期

关键词：

HUMAN CEREBRAL-CORTEX; PROJECTION NEURON; PREFRONTAL CORTEX; CORTICAL-NEURONS; HUMAN NEOCORTEX; RADIAL GLIA; EVOLUTION; IDENTITY; SPECIFICATION; INSIGHTS;

D O I：

10.1016/j.neuron.2012.12.011

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：440 / 456

页数：17

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