Microglia Biology: One Century of Evolving Concepts

Cell, Journal Year: 2019, Volume and Issue: 179(2), P. 292 - 311

Published: Oct. 1, 2019

Language: Английский

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A human cell atlas of fetal gene expression

Science, Journal Year: 2020, Volume and Issue: 370(6518)

Published: Nov. 12, 2020

The genomics of human development Understanding the trajectory a developing requires an understanding how genes are regulated and expressed. Two papers now present pooled approach using three levels combinatorial indexing to examine single-cell gene expression chromatin landscapes from 15 organs in fetal samples. Cao et al. focus on measurements RNA broadly distributed cell types provide insights into organ specificity. Domcke examined accessibility cells these identify regulatory elements that regulate expression. Together, analyses generate comprehensive atlases early development. Science , this issue p. eaba7721 eaba7612

Language: Английский

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Modeling Alzheimer’s disease with iPSC-derived brain cells

Molecular Psychiatry, Journal Year: 2019, Volume and Issue: 25(1), P. 148 - 167

Published: Aug. 7, 2019

Alzheimer’s disease is a devastating neurodegenerative disorder with no cure. Countless promising therapeutics have shown efficacy in rodent models yet failed to benefit human patients. While hope remains that earlier intervention existing will improve outcomes, it becoming increasingly clear new approaches understand and combat the pathophysiology of are needed. Human induced pluripotent stem cell (iPSC) technologies changed face preclinical research iPSC-derived types being utilized study an array conditions, including disease. All major brain can now be differentiated from iPSCs, while complex co-culture systems developed facilitate neuroscience research. Many cellular functions perturbed recapitulated using cells vitro, platforms beginning yield insights into interactions occur between during neurodegeneration. Further, iPSC-based genome editing tools critical understanding roles numerous genes mutations found modify risk past decade. still their relative infancy, these developing hold considerable promise push forward efforts other disorders.

Language: Английский

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Microglia and Central Nervous System–Associated Macrophages—From Origin to Disease Modulation

Annual Review of Immunology, Journal Year: 2021, Volume and Issue: 39(1), P. 251 - 277

Published: Feb. 9, 2021

The immune system of the central nervous (CNS) consists primarily innate cells. These are highly specialized macrophages found either in parenchyma, called microglia, or at CNS interfaces, such as leptomeningeal, perivascular, and choroid plexus macrophages. While they were thought phagocytes, their function extends well beyond simple removal cell debris during development diseases. Brain-resident cells to be plastic, long-lived, host an outstanding number risk genes for multiple pathologies. As a result, now considered most suitable targets modulating Additionally, recent single-cell technologies enhanced our molecular understanding origins, fates, interactomes, functional statesduring health perturbation. Here, we review current state challenges myeloid biology treatment options related

Language: Английский

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Organoids by design

Science, Journal Year: 2019, Volume and Issue: 364(6444), P. 956 - 959

Published: June 6, 2019

Organoids are multicellular structures that can be derived from adult organs or pluripotent stem cells. Early versions of organoids range simple epithelial to complex, disorganized tissues with large cellular diversity. The current challenge is engineer complexity into in a controlled manner results organized assembly and acquisition tissue function. These efforts have relied on studies organ during embryonic development resulted the multilayer higher-order functions. We discuss how next generation designed by means an engineering-based narrative design control patterning, assembly, morphogenesis, growth,

Language: Английский

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Immune cell regulation of glia during CNS injury and disease

Nature reviews. Neuroscience, Journal Year: 2020, Volume and Issue: 21(3), P. 139 - 152

Published: Feb. 10, 2020

Language: Английский

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The pro-remyelination properties of microglia in the central nervous system

Nature Reviews Neurology, Journal Year: 2019, Volume and Issue: 15(8), P. 447 - 458

Published: June 29, 2019

Language: Английский

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APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer’s disease patient iPSC-derived cerebral organoids

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Nov. 2, 2020

Abstract APOE4 is the strongest genetic risk factor associated with late-onset Alzheimer’s disease (AD). To address underlying mechanism, we develop cerebral organoid models using induced pluripotent stem cells (iPSCs) APOE ε3/ε3 or ε4/ε4 genotype from individuals either normal cognition AD dementia. Cerebral organoids patients carrying show greater apoptosis and decreased synaptic integrity. While patient-derived have increased levels of Aβ phosphorylated tau compared to healthy subject-derived organoids, exacerbates pathology in both organoids. Transcriptomics analysis by RNA-sequencing reveals that are an enhancement stress granules disrupted RNA metabolism. Importantly, isogenic conversion APOE3 attenuates -related phenotypes patients. Together, our study human iPSC-organoids recapitulates suggests degenerative pathways contributing pathogenesis.

Language: Английский

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Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo

Nature Neuroscience, Journal Year: 2020, Volume and Issue: 23(12), P. 1496 - 1508

Published: Nov. 2, 2020

Language: Английский

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Generation of vascularized brain organoids to study neurovascular interactions

eLife, Journal Year: 2022, Volume and Issue: 11

Published: May 4, 2022

Brain organoids have been used to recapitulate the processes of brain development and related diseases. However, lack vasculatures, which regulate neurogenesis disorders, limits utility organoids. In this study, we induced vessel organoids, respectively, then fused two types together obtain vascularized The were engrafted with robust vascular network-like structures exhibited increased number neural progenitors, in line possibility that vessels development. Fusion also contained functional blood–brain barrier-like structures, as well microglial cells, a specific population immune cells brain. incorporated microglia responded actively stimuli showed ability engulfing synapses. Thus, fusion established study allow modeling interactions between neuronal non-neuronal components vitro, particularly vasculature niche.

Language: Английский

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