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Identification of TGFβ signalling as a regulator of interneuron neurogenesis in a human pluripotent stem cell model

Cruz Santos, Maria and Li, Meng 2021. Identification of TGFβ signalling as a regulator of interneuron neurogenesis in a human pluripotent stem cell model. Neuronal Signaling 5 (4) , NS20210020. 10.1042/NS20210020

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Abstract

Cortical interneurons are GABAergic inhibitory cells that connect locally in the neocortex and play a pivotal role in shaping cortical network activities. Dysfunction of these cells is believed to lead to runaway excitation underlying seizure-based diseases, such as epilepsy, autism, and schizophrenia. There is a growing interest in using cortical interneurons derived from human pluripotent stem cells for understanding their complex development and for modeling neuropsychiatric diseases. Here, we report the identification of a novel role of TGFβ signaling in modulating interneuron progenitor maintenance and neuronal differentiation. TGFβ signaling inhibition suppresses terminal differentiation of interneuron progenitors while exogenous TGFβ3 accelerates the transition of progenitors into postmitotic neurons. We provide evidence that TGFb signaling exerts this function via regulating cell cycle length of the NKX2.1+ neural progenitors. Together, this study represents a useful platform for studying human interneuron development and interneuron associated neurological diseases with human pluripotent stem cells.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information: This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY
Publisher: Portland Press
ISSN: 2059-6553
Date of First Compliant Deposit: 12 November 2021
Date of Acceptance: 11 November 2021
Last Modified: 24 Jan 2022 12:34
URI: https://orca.cardiff.ac.uk/id/eprint/145459

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