Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus

Rasetto NB, Giacomini D, Berardino AA, Waichman TV, Beckel MS, Di Bella DJ, Brown J, Davies-Sala MG, Gerhardinger C, Lie DC, Arlotta P, Chernomoretz A, Schinder AF (2024)

Publication Language: English

Publication Type: Journal article

Publication year: 2024

Journal

Science Advances American Association for the Advancement of Science

Book Volume: 10

Article Number: eadp6039

Journal Issue: 29

DOI: 10.1126/sciadv.adp6039

Abstract

The adult hippocampus generates new granule cells (aGCs) with functional capabilities that convey unique forms of plasticity to the preexisting circuits. While early differentiation of adult radial glia-like cells (RGLs) has been studied extensively, the molecular mechanisms guiding the maturation of postmitotic neurons remain unknown. Here, we used a precise birthdating strategy to study aGC differentiation using single-nuclei RNA sequencing. Transcriptional profiling revealed a continuous trajectory from RGLs to mature aGCs, with multiple immature stages bearing increasing levels of effector genes supporting growth, excitability, and synaptogenesis. Analysis of differential gene expression, pseudo-time trajectory, and transcription factors (TFs) revealed critical transitions defining four cellular states: quiescent RGLs, proliferative progenitors, immature aGCs, and mature aGCs. Becoming mature aGCs involved a transcriptional switch that shuts down pathways promoting cell growth, such SoxC TFs, to activate programs that likely control neuronal homeostasis. aGCs overexpressing Sox4 or Sox11 remained immature. Our results unveil precise molecular mechanisms driving adult RGLs through the pathway of neuronal differentiation.

Authors with CRIS profile

Dieter Chichung Lie Professur für Molekulare Medizin mit dem Schwerpunkt Molekulare Bildgebung

Involved external institutions

Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA)

Argentina (AR) Harvard University

United States (USA) (US)

How to cite

APA:

Rasetto, N.B., Giacomini, D., Berardino, A.A., Waichman, T.V., Beckel, M.S., Di Bella, D.J.,... Schinder, A.F. (2024). Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus. Science Advances, 10(29). https://doi.org/10.1126/sciadv.adp6039

MLA:

Rasetto, Natalí B., et al. "Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus." Science Advances 10.29 (2024).

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