TY - JOUR
T1 - Adult human subventricular zone microglia promote a pro-neurogenic niche for neuronal progenitors in Parkinson's disease
AU - Pecoraro, Sara
AU - Verkerke, Marloes
AU - Sluijs, Jacqueline A
AU - van Het Hof, Bert
AU - van der Pol, Susanne M A
AU - van Strien, Miriam E
AU - van der Kant, Rik
AU - de Vries, Carlie
AU - de Vries, Helga E
AU - van de Berg, Wilma D J
AU - Hol, Elly M
AU - Donega, Vanessa
N1 - Copyright © 2025. Published by Elsevier Inc.
PY - 2025/6/12
Y1 - 2025/6/12
N2 - Neural stem cells (NSCs) in the subventricular zone (SVZ) of the mammalian brain become increasingly quiescent with aging, which correlates to increased inflammatory signals in the SVZ. Targeting cells that secrete inflammatory signals, such as microglia, could potentially re-activate NSCs. In this study, we characterized CD11b-positive microglia isolated from post-mortem SVZ from non-demented control (Aged), Alzheimer's disease (AD), and Parkinson's disease (PD) by single-cell and bulk RNA sequencing. Our transcriptome data revealed changes in gene signature in SVZ microglia from PD and AD, highlighting a disease-dependent response. Culture of iPSC-derived NSCs with supernatant from Aged, PD, and AD SVZ microglia showed an increase in proliferation and neuronal differentiation in the PD condition. Furthermore, we identified NR4A2, a transcription factor that promotes an anti-inflammatory microglia state, as a potential molecular mechanism that promotes a pro-neurogenic microglia phenotype. Altogether, our work identified a pro-neurogenic subpopulation of SVZ microglia that could be a novel target to promote repair in neurodegenerative diseases.
AB - Neural stem cells (NSCs) in the subventricular zone (SVZ) of the mammalian brain become increasingly quiescent with aging, which correlates to increased inflammatory signals in the SVZ. Targeting cells that secrete inflammatory signals, such as microglia, could potentially re-activate NSCs. In this study, we characterized CD11b-positive microglia isolated from post-mortem SVZ from non-demented control (Aged), Alzheimer's disease (AD), and Parkinson's disease (PD) by single-cell and bulk RNA sequencing. Our transcriptome data revealed changes in gene signature in SVZ microglia from PD and AD, highlighting a disease-dependent response. Culture of iPSC-derived NSCs with supernatant from Aged, PD, and AD SVZ microglia showed an increase in proliferation and neuronal differentiation in the PD condition. Furthermore, we identified NR4A2, a transcription factor that promotes an anti-inflammatory microglia state, as a potential molecular mechanism that promotes a pro-neurogenic microglia phenotype. Altogether, our work identified a pro-neurogenic subpopulation of SVZ microglia that could be a novel target to promote repair in neurodegenerative diseases.
KW - Microglia
KW - Neurogenesis
KW - Human subventricular zone
KW - Parkinson’s disease
KW - Alzheimer’s disease
KW - NR4A2
KW - (single-cell) RNA sequencing
U2 - 10.1016/j.bbi.2025.06.017
DO - 10.1016/j.bbi.2025.06.017
M3 - Article
C2 - 40516636
SN - 0889-1591
VL - 129
SP - 318
EP - 334
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -