Modeling Human Cortical Development in Vitro Using Induced Pluripotent Stem Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2012 Jul 5

PMID 22761314

Citations 273

Authors

Jessica Mariani

Maria Vittoria Simonini

Dean Palejev

Livia Tomasini

Gianfilippo Coppola

Anna M Szekely

Tamas L Horvath

Flora M Vaccarino

Affiliations

Soon will be listed here.

Abstract

Human induced pluripotent stem cells (hiPSCs) are emerging as a tool for understanding human brain development at cellular, molecular, and genomic levels. Here we show that hiPSCs grown in suspension in the presence of rostral neuralizing factors can generate 3D structures containing polarized radial glia, intermediate progenitors, and a spectrum of layer-specific cortical neurons reminiscent of their organization in vivo. The hiPSC-derived multilayered structures express a gene expression profile typical of the embryonic telencephalon but not that of other CNS regions. Their transcriptome is highly enriched in transcription factors controlling the specification, growth, and patterning of the dorsal telencephalon and displays highest correlation with that of the early human cerebral cortical wall at 8-10 wk after conception. Thus, hiPSC are capable of enacting a transcriptional program specifying human telencephalic (pallial) development. This model will allow the study of human brain development as well as disorders of the human cerebral cortex.

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