LIF signaling regulates outer radial glial to interneuron fate during human cortical development

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..

Radial glial (RG) development is essential for cerebral cortex growth and organization. In humans, the outer radial glia (oRG) subtype is expanded and gives rise to diverse neurons and glia. However, the mechanisms regulating oRG differentiation are unclear. oRG cells express leukemia-inhibitory factor (LIF) receptors during neurogenesis, and consistent with a role in stem cell self-renewal, LIF perturbation impacts oRG proliferation in cortical tissue and organoids. Surprisingly, LIF treatment also increases the production of inhibitory interneurons (INs) in cortical cultures. Comparative transcriptomic analysis identifies that the enhanced IN population resembles INs produced in the caudal ganglionic eminence. To evaluate whether INs could arise from oRGs, we isolated primary oRG cells and cultured them with LIF. We observed the production of INs from oRG cells and an increase in IN abundance following LIF treatment. Our observations suggest that LIF signaling regulates the capacity of oRG cells to generate INs.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:30

Enthalten in:

Cell stem cell - 30(2023), 10 vom: 05. Okt., Seite 1382-1391.e5

Sprache:

Englisch

Beteiligte Personen:

Andrews, Madeline G [VerfasserIn]
Siebert, Clara [VerfasserIn]
Wang, Li [VerfasserIn]
White, Matthew L [VerfasserIn]
Ross, Jayden [VerfasserIn]
Morales, Raul [VerfasserIn]
Donnay, Megan [VerfasserIn]
Bamfonga, Gradi [VerfasserIn]
Mukhtar, Tanzila [VerfasserIn]
McKinney, Arpana Arjun [VerfasserIn]
Gemenes, Kaila [VerfasserIn]
Wang, Shaohui [VerfasserIn]
Bi, Qiuli [VerfasserIn]
Crouch, Elizabeth E [VerfasserIn]
Parikshak, Neelroop [VerfasserIn]
Panagiotakos, Georgia [VerfasserIn]
Huang, Eric [VerfasserIn]
Bhaduri, Aparna [VerfasserIn]
Kriegstein, Arnold R [VerfasserIn]

Links:

Volltext

Themen:

Cerebral cortex
Human development
Inhibitory interneurons
Journal Article
Mechanisms of differentiation
Neural progenitors
Neurodevelopment
Organoid models
Pluripotent stem cells
Radial glia
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Signaling mechanisms

Anmerkungen:

Date Completed 26.10.2023

Date Revised 22.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.stem.2023.08.009

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM361707207