Modeling Down Syndrome with Patient iPSCs Reveals Cellular and Migration Deficits of GABAergic Neurons

Stem Cell Reports
Hai-Qin HuoYan Liu

Abstract

The brain of Down syndrome (DS) patients exhibits fewer interneurons in the cerebral cortex, but its underlying mechanism remains unknown. By morphometric analysis of cortical interneurons generated from DS and euploid induced pluripotent stem cells (iPSCs), we found that DS GABA neurons are smaller and with fewer neuronal processes. The proportion of calretinin over calbindin GABA neurons is reduced, and the neuronal migration capacity is decreased. Such phenotypes were replicated following transplantation of the DS GABAergic progenitors into the mouse medial septum. Gene expression profiling revealed altered cell migratory pathways, and correction of the PAK1 pathway mitigated the cell migration deficit in vitro. These results suggest that impaired migration of DS GABAergic neurons may contribute to the reduced number of interneurons in the cerebral cortex and hippocampus in DS patients.

Citations

Mar 16, 2019·Annals of the New York Academy of Sciences·M Catarina Silva, Stephen J Haggarty
Oct 13, 2018·Science·Raquel RealVincenzo De Paola
Jun 17, 2020·Seminars in Cell & Developmental Biology·Nikolai J FedorchakRandolph S Ashton
Feb 16, 2021·Frontiers in Cell and Developmental Biology·Manuela D MitsogiannisEve Seuntjens

Methods Mentioned

BETA
dissection
RNA-seq
Assay
PCR

Related Concepts

Pak1 protein, mouse
Metazoa
Brain
Cell Differentiation Process
Cell Motility
Cell Survival
Trisomy 21, Mitotic Nondisjunction
Interneurons
Somatofalk
Neurites

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