Adult microglial TGFβ1 is required for microglia homeostasis via an autocrine mechanism to maintain cognitive function in mice DOI Creative Commons
Alicia Bedolla,

Elliot Wegman,

Max Weed

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 21, 2024

Abstract While TGF-β signaling is essential for microglial function, the cellular source of TGF-β1 ligand and its spatial regulation remains unclear in adult CNS. Our data supports that microglia but not astrocytes or neurons are primary producers ligands needed homeostasis. Microglia- Tgfb1 KO leads to activation featuring a dyshomeostatic transcriptome resembles disease-associated, injury-associated, aged microglia, suggesting self-produced important Astrocytes MG-Tgfb1 inducible (i)KO mice show profile closely aligned with an LPS-associated astrocyte profile. Additionally, using sparse mosaic single-cell we established autocrine mechanism signaling. Here MG- iKO present cognitive deficits, supporting precise derived from required maintenance brain homeostasis normal function brain.

Language: Английский

Microglia states and nomenclature: A field at its crossroads DOI Creative Commons
Rosa Chiara Paolicelli, Amanda Sierra, Beth Stevens

et al.

Neuron, Journal Year: 2022, Volume and Issue: 110(21), P. 3458 - 3483

Published: Nov. 1, 2022

Language: Английский

Citations

1043
Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation DOI Creative Commons
Anthony Fernández-Castañeda, Peiwen Lu, Anna C. Geraghty

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(14), P. 2452 - 2468.e16

Published: June 13, 2022

COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection found white-matter-selective in mice humans. Following mild mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused neurogenesis. Concordantly, humans lasting post-COVID exhibit levels. Compared SARS-CoV-2, influenza similar patterns reactivity, oligodendrocyte loss, at early time points, but after influenza, only pathology persisted. These findings illustrate neuropathophysiology cancer therapy may contribute to impairment following even COVID.

Language: Английский

Citations

385
TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways DOI Creative Commons
Shoutang Wang, Raki Sudan, Vincent Peng

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(22), P. 4153 - 4169.e19

Published: Oct. 1, 2022

Language: Английский

Citations

214
Microglia ferroptosis is regulated by SEC24B and contributes to neurodegeneration DOI Creative Commons
Sean K. Ryan,

Matija Zelic,

Yingnan Han

et al.

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 26(1), P. 12 - 26

Published: Dec. 19, 2022

Iron dysregulation has been implicated in multiple neurodegenerative diseases, including Parkinson's disease (PD). Iron-loaded microglia are frequently found affected brain regions, but how iron accumulation influences physiology and contributes to neurodegeneration is poorly understood. Here we show that human induced pluripotent stem cell-derived grown a tri-culture system highly responsive susceptible ferroptosis, an iron-dependent form of cell death. Furthermore, overload causes marked shift the microglial transcriptional state overlaps with transcriptomic signature PD postmortem microglia. Our data also this response neurodegeneration, as removal from substantially delayed iron-induced neurotoxicity. To elucidate mechanisms regulating microglia, performed genome-wide CRISPR screen identified novel regulators vesicle trafficking gene SEC24B. These suggest critical role for ferroptosis neurodegeneration.

Language: Английский

Citations

205
Dissecting the treatment-naive ecosystem of human melanoma brain metastasis DOI Creative Commons
Jana Biermann, Johannes C. Melms, Amit Dipak Amin

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(14), P. 2591 - 2608.e30

Published: July 1, 2022

Language: Английский

Citations

124
Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer’s disease DOI
Hu Zeng, Jiahao Huang, Haowen Zhou

et al.

Nature Neuroscience, Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 2, 2023

Language: Английский

Citations

114
Directed evolution of adeno-associated virus for efficient gene delivery to microglia DOI
Rui Lin,

Youtong Zhou,

Ting Yan

et al.

Nature Methods, Journal Year: 2022, Volume and Issue: 19(8), P. 976 - 985

Published: July 25, 2022

Language: Английский

Citations

110
Early Alzheimer’s disease pathology in human cortex involves transient cell states DOI Creative Commons
Vahid Gazestani, Tushar Kamath, Naeem Nadaf

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(20), P. 4438 - 4453.e23

Published: Sept. 1, 2023

Language: Английский

Citations

101
Insights into Alzheimer’s disease from single-cell genomic approaches DOI
Mitchell H. Murdock, Li‐Huei Tsai

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(2), P. 181 - 195

Published: Jan. 2, 2023

Language: Английский

Citations

98
The molecular cytoarchitecture of the adult mouse brain DOI Creative Commons
Jonah Langlieb, Nina Sachdev, Karol S. Balderrama

et al.

Nature, Journal Year: 2023, Volume and Issue: 624(7991), P. 333 - 342

Published: Dec. 13, 2023

Abstract The function of the mammalian brain relies upon specification and spatial positioning diversely specialized cell types. Yet, molecular identities types their positions within individual anatomical structures remain incompletely known. To construct a comprehensive atlas in each structure, we paired high-throughput single-nucleus RNA sequencing with Slide-seq 1,2 —a recently developed transcriptomics method near-cellular resolution—across entire mouse brain. Integration these datasets revealed type composition neuroanatomical structure. Cell diversity was found to be remarkably high midbrain, hindbrain hypothalamus, most clusters requiring combination at least three discrete gene expression markers uniquely define them. Using data, framework for genetically accessing type, comprehensively characterized neuropeptide neurotransmitter signalling, elucidated region-specific specializations activity-regulated ascertained heritability enrichment neurological psychiatric phenotypes. These available as an online resource ( www.BrainCellData.org ), should find diverse applications across neuroscience, including construction new genetic tools prioritization specific circuits study diseases.

Language: Английский

Citations

97