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BRIEF RESEARCH REPORT article

Front. Neurosci.
Sec. Neurogenesis
Volume 18 - 2024 | doi: 10.3389/fnins.2024.1400963

Single cell RNA sequencing of aging neural progenitors reveals loss of excitatory neuron potential and a population with transcriptional immune response

Provisionally accepted
Jonas Fritze Jonas Fritze 1,2*Stefan Lang Stefan Lang 1,3Mikael Sommarin Mikael Sommarin 1,4Shamit Soneji Shamit Soneji 1,3Henrik Ahlenius Henrik Ahlenius 1,2
  • 1 Lund Stem Cell Center, Faculty of Medicine, Lund University, Lund, Skane County, Sweden
  • 2 Department of Experimental Medical Science, Stem Cells, Aging and Neurodegeneration group, Lund University, Faculty of Medicine, Lund, Sweden
  • 3 Division of Molecular Hematology, Computational Genomics group, Lund University, Faculty of Medicine, Lund, Sweden
  • 4 Division of Molecular Hematology, Lund Stem Cell Center, Faculty of Medicine, Lund University, Lund, Sweden

The final, formatted version of the article will be published soon.

    In the adult murine brain, neural stem cells (NSCs) reside in two main niches, the dentate gyrus (DG), and the subventricular zone (SVZ). In the DG, NSCs give rise to intermediate progenitors (IPs) that differentiate into excitatory neurons, while progenitors in the SVZ migrate to the olfactory bulb (OB) where they mainly differentiate into inhibitory interneurons.Neurogenesis, the production of new neurons, persists throughout life but decrease dramatically during aging, concomitantly with increased inflammation. Many cell types, including microglia, undergo dramatic transcriptional changes but few such changes have been detected in neural progenitors. Furthermore, transcriptional profiles in progenitors from different neurogenic regions have not been compared at single cell level, and little is known about how they are affected by agerelated inflammation.We have generated a single cell RNA sequencing dataset enriched for IPs, which revealed that most aged neural progenitors only acquire minor transcriptional changes. However, progenitors set to become excitatory neurons decrease faster than others. In addition, a population in the aged SVZ, not detected in the OB, acquired major transcriptional activation related to immune responses. This suggests that differences in age related neurogenic decline between regions is not due to tissue differences but rather cell type specific intrinsic transcriptional programs, and that subset of neuroblasts in the SVZ react strongly to age related inflammatory cues.

    Keywords: Neurogenesis, Aging, Intermediate progenitors, neuroblasts, immune response, Dentate Gyrus, Subventricular zone, excitatory

    Received: 14 Mar 2024; Accepted: 08 Jul 2024.

    Copyright: © 2024 Fritze, Lang, Sommarin, Soneji and Ahlenius. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jonas Fritze, Lund Stem Cell Center, Faculty of Medicine, Lund University, Lund, 221 84, Skane County, Sweden

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.