Single-cell transcriptomics reveals conserved regulatory networks in human and mouse interneuron development

Keefe, Francesca, Monzon Sandoval, Jimena, Rosser, Anne E. ORCID: https://orcid.org/0000-0002-4716-4753, Webber, Caleb ORCID: https://orcid.org/0000-0001-8063-7674 and Li, Meng ORCID: https://orcid.org/0000-0002-4803-4643 2023. Single-cell transcriptomics reveals conserved regulatory networks in human and mouse interneuron development. International Journal of Molecular Sciences 24 (9) , 8122. 10.3390/ijms24098122

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Publisher:	MDPI
ISSN:	1422-0067
Funders:	MRC
Date of First Compliant Deposit:	10 May 2023
Date of Acceptance:	27 April 2023
Last Modified:	28 Feb 2024 12:05
URI:	https://orca.cardiff.ac.uk/id/eprint/159398

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