Single-Cell Transcriptomics Reveals Conserved Regulatory Networks in Human and Mouse Interneuron Development

Abstract

Inhibitory GABAergic interneurons originate in the embryonic medial ganglionic eminence (MGE) and control network activity in the neocortex. Dysfunction of these cells is believed to lead to runaway excitation underlying seizure-based neurological disorders such as epilepsy, autism, and schizophrenia. Despite their importance in heath and disease, our knowledge about the development of this diverse neuronal population remains incomplete. Here we conducted single-cell RNA sequencing (scRNA-seq) of human foetal MGE from 10 to 15 weeks post conception. These MGE tissues are composed of largely cycling progenitors and immature post-mitotic interneurons with characteristic regional marker expression. Analysis of integrated human and mouse MGE data revealed species-conserved transcriptomic profiles and regulatory programs. Moreover, we identified novel candidate transcription regulators for human interneuron differentiation. These findings provide a framework for in vitro modelling of interneuron development and a strategy for potentially enhancing interneuron production from human pluripotent stem cells.

MAPKAP1 orchestrates macrophage polarization and lipid metabolism in fatty liver-enhanced colorectal cancer

“…The amplified cDNA should be constructed into a library, and single-cell sequencing should be performed on the HiSeq 4000 Illumina platform. The sequencing should use paired-end reads with a read length of 2 × 75 bp and approximately 20,000 reads per cell [29] .…”

Patterning ganglionic eminences in developing human brain organoids using a morphogen-gradient-inducing device

“… 13 , 17 , 18 While much of what we know of the GEs has come from animal models, recent characterizations of postmortem human fetal brain tissue have aided in enlightening the unique transcriptomes of the human GEs. 19 , 20 , 21 , 22 , 23 Due to the unique progenitor pools of the GEs, reproducing the anatomical regionalization in GEs is a key component of accurately modeling brain development.…”

Parvalbumin Interneuron Dysfunction in Neurological Disorders: Focus on Epilepsy and Alzheimer’s Disease

“…They also play an important role in cortical sensory plasticity during development and adulthood [5,6]. Single-cell transcriptomics has revealed evolutionary conservation of regulatory networks during inhibitory interneuron development in humans and animals [7,8]. Clearly, proper functional connectivity and plasticity of neuronal networks within the developing and mature brain are dependent on a highly efficient and precisely coordinated GABAergic signaling system.…”