Fate mapping of neural stem cell niches reveals distinct origins of human cortical astrocytes DOI Open Access
Denise E. Allen, Kevin C. Donohue, Cathryn R. Cadwell

et al.

Science, Journal Year: 2022, Volume and Issue: 376(6600), P. 1441 - 1446

Published: May 19, 2022

Progenitors of the developing human neocortex reside in ventricular and outer subventricular zones (VZ OSVZ, respectively). However, whether cells derived from these niches have similar developmental fates is unknown. By performing fate mapping primary tissue, we demonstrate that astrocytes populate anatomically distinct layers. Cortical plate emerge VZ progenitors proliferate locally, while putative white matter are morphologically heterogeneous both OSVZ progenitors. Furthermore, via single-cell sequencing defined astrocyte subtypes using Patch-seq, identify molecular distinctions between VZ-derived cortical OSVZ-derived persist into adulthood. Together, our study highlights a complex role for cell lineage diversification neocortical astrocytes.

Language: Английский

Molecular basis of astrocyte diversity and morphology across the CNS in health and disease DOI
Fumito Endo, Atsushi Kasai, Joselyn S. Soto

et al.

Science, Journal Year: 2022, Volume and Issue: 378(6619)

Published: Nov. 3, 2022

Astrocytes, a type of glia, are abundant and morphologically complex cells. Here, we report astrocyte molecular profiles, diversity, morphology across the mouse central nervous system (CNS). We identified shared region-specific astrocytic genes functions explored cellular origins their regional diversity. gene networks correlated with morphology, several which unexpectedly contained Alzheimer’s disease (AD) risk genes. CRISPR/Cas9–mediated reduction candidate reduced morphological complexity resulted in cognitive deficits. The same were down-regulated human AD, an AD model that displayed other brain disorders. thus provide comprehensive data on diversity mechanisms CNS basis health disease.

Language: Английский

Citations

328

Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases DOI Creative Commons
Jian Sheng Loh, Wen Qi Mak, Li Tan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Language: Английский

Citations

283

Astrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders DOI
Ashley N. Brandebura, Adrien Paumier, Tarik Seref Onur

et al.

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 24(1), P. 23 - 39

Published: Oct. 31, 2022

Language: Английский

Citations

267

Multiple sclerosis: Neuroimmune crosstalk and therapeutic targeting DOI Creative Commons
Marc Charabati, Michael A. Wheeler, Howard L. Weiner

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(7), P. 1309 - 1327

Published: March 1, 2023

Language: Английский

Citations

126

Astrocytes in the initiation and progression of epilepsy DOI
Annamaria Vezzani, Teresa Ravizza, Peter Bedner

et al.

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(12), P. 707 - 722

Published: Oct. 24, 2022

Language: Английский

Citations

111

Neuroinflammation: An astrocyte perspective DOI Open Access
Hong‐Gyun Lee, Joon-Hyuk Lee, Lucas E. Flausino

et al.

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(721)

Published: Nov. 8, 2023

Astrocytes are abundant glial cells in the central nervous system (CNS) that play active roles health and disease. Recent technologies have uncovered functional heterogeneity of astrocytes their extensive interactions with other cell types CNS. In this Review, we highlight intricate between astrocytes, CNS-resident cells, CNS-infiltrating as well potential therapeutic value context inflammation neurodegeneration.

Language: Английский

Citations

92

Droplet-based forward genetic screening of astrocyte–microglia cross-talk DOI
Michael A. Wheeler, Iain C. Clark, Hong‐Gyun Lee

et al.

Science, Journal Year: 2023, Volume and Issue: 379(6636), P. 1023 - 1030

Published: March 10, 2023

Cell-cell interactions in the central nervous system play important roles neurologic diseases. However, little is known about specific molecular pathways involved, and methods for their systematic identification are limited. Here, we developed a forward genetic screening platform that combines CRISPR-Cas9 perturbations, cell coculture picoliter droplets, microfluidic-based fluorescence-activated droplet sorting to identify mechanisms of cell-cell communication. We used SPEAC-seq (systematic perturbation encapsulated associated cells followed by sequencing), combination with vivo microglia-produced amphiregulin as suppressor disease-promoting astrocyte responses multiple sclerosis preclinical models clinical samples. Thus, enables high-throughput communication mechanisms.

Language: Английский

Citations

74

Astrocyte–neuron subproteomes and obsessive–compulsive disorder mechanisms DOI Creative Commons
Joselyn S. Soto, Yasaman Jami‐Alahmadi,

Jakelyn Chacon

et al.

Nature, Journal Year: 2023, Volume and Issue: 616(7958), P. 764 - 773

Published: April 12, 2023

Astrocytes and neurons extensively interact in the brain. Identifying astrocyte neuron proteomes is essential for elucidating protein networks that dictate their respective contributions to physiology disease. Here we used cell-specific subcompartment-specific proximity-dependent biotinylation1 study of striatal astrocytes vivo. We evaluated cytosolic plasma membrane compartments discover how these cells differ at level signalling machinery. also assessed subcellular astrocytes, including end feet fine processes, reveal subproteomes molecular basis homeostatic functions. Notably, SAPAP3 (encoded by Dlgap3), which associated with obsessive-compulsive disorder (OCD) repetitive behaviours2-8, was detected high levels enriched within specific subcompartments where it regulated actin cytoskeleton organization. Furthermore, genetic rescue experiments combined behavioural analyses assessments a mouse model OCD4 lacking revealed distinct astrocytic neuronal anxiety-related OCD-like phenotypes. Our data define major pathways. Moreover, they vary between physiological both mechanisms contribute OCD phenotypes mice. indicate therapeutic strategies target may be useful explore potentially other brain disorders.

Language: Английский

Citations

58

Astrocyte morphology DOI Creative Commons
Katherine T. Baldwin, Keith K. Murai, Baljit S. Khakh

et al.

Trends in Cell Biology, Journal Year: 2023, Volume and Issue: 34(7), P. 547 - 565

Published: Oct. 26, 2023

Astrocytes are predominant glial cells that tile the central nervous system (CNS). A cardinal feature of astrocytes is their complex and visually enchanting morphology, referred to as bushy, spongy, star-like. precept this review such morphological shapes evolved allow contact signal with diverse at a range distances in order sample, regulate, contribute extracellular milieu, thus participate widely cell–cell signaling during physiology disease. The recent use improved imaging methods cell-specific molecular evaluations has revealed new information on structural organization underpinnings astrocyte mechanisms morphogenesis, contributions disease states reduced morphology. These insights have reignited interest complexity cornerstone fundamental biology critical substrate for multicellular spatial physiological interactions CNS.

Language: Английский

Citations

53

Identification of astrocyte regulators by nucleic acid cytometry DOI
Iain C. Clark, Michael A. Wheeler, Hong‐Gyun Lee

et al.

Nature, Journal Year: 2023, Volume and Issue: 614(7947), P. 326 - 333

Published: Jan. 4, 2023

Language: Английский

Citations

50