Molecularly cleavable bioinks facilitate high-performance digital light processing-based bioprinting of functional volumetric soft tissues DOI Creative Commons
Mian Wang, Wanlu Li, Jin Hao

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: June 9, 2022

Digital light processing bioprinting favors biofabrication of tissues with improved structural complexity. However, soft-tissue fabrication this method remains a challenge to balance the physical performances bioinks for high-fidelity and suitable microenvironments encapsulated cells thrive. Here, we propose molecular cleavage approach, where hyaluronic acid methacrylate (HAMA) is mixed gelatin methacryloyl achieve high-performance bioprinting, followed by selectively enzymatic digestion HAMA, resulting in tissue-matching mechanical properties without losing complexity fidelity. Our allows cellular morphological functional improvements across multiple bioprinted tissue types featuring wide range stiffness, from muscles brain, softest organ human body. This platform endows us biofabricate mechanically precisely tunable constructs meet biological function requirements target tissues, potentially paving way broad applications model engineering.

Language: Английский

Towards an Understanding of Synapse Formation DOI Creative Commons
Thomas C. Südhof

Neuron, Journal Year: 2018, Volume and Issue: 100(2), P. 276 - 293

Published: Oct. 1, 2018

Language: Английский

Citations

590
Synaptic proximity enables NMDAR signalling to promote brain metastasis DOI
Qiqun Zeng, Iacovos P. Michael, Peng Zhang

et al.

Nature, Journal Year: 2019, Volume and Issue: 573(7775), P. 526 - 531

Published: Sept. 18, 2019

Language: Английский

Citations

419
The Emerging Nature of Astrocyte Diversity DOI Open Access
Baljit S. Khakh, Benjamin Deneen

Annual Review of Neuroscience, Journal Year: 2019, Volume and Issue: 42(1), P. 187 - 207

Published: July 8, 2019

Astrocytes are morphologically complex, ubiquitous cells that viewed as a homogeneous population tiling the entire central nervous system (CNS). However, this view has been challenged in last few years with availability of RNA sequencing, immunohistochemistry, electron microscopy, morphological reconstruction, and imaging data. These studies suggest astrocytes represent diverse they display brain area– disease–specific properties functions. In review, we summarize these observations, emphasize areas where clear conclusions can be made, discuss potential unifying themes. We also identify knowledge gaps need to addressed order exploit astrocyte diversity biological phenomenon physiological relevance CNS. thus provide summary perspective on vertebrate

Language: Английский

Citations

403
Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease DOI Creative Commons
Shun‐Fat Lau, Han Cao, Amy K.Y. Fu

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(41), P. 25800 - 25809

Published: Sept. 28, 2020

Alzheimer's disease (AD) is the most common form of dementia but has no effective treatment. A comprehensive investigation cell type-specific responses and cellular heterogeneity in AD required to provide precise molecular targets for therapeutic development. Accordingly, we perform single-nucleus transcriptome analysis 169,496 nuclei from prefrontal cortical samples patients normal control (NC) subjects. Differential shows that transcriptomic changes are associated with disruption biological processes including angiogenesis, immune activation, synaptic signaling, myelination. Subcluster reveals compared NC brains, brains contain fewer neuroprotective astrocytes oligodendrocytes. Importantly, our findings show a subpopulation angiogenic endothelial cells induced brain AD. These exhibit increased expression growth factors their receptors (i.e.,

Language: Английский

Citations

361
Astrocytes, neurons, synapses: a tripartite view on cortical circuit development DOI Creative Commons
Isabella Farhy-Tselnicker, Nicola J. Allen

Neural Development, Journal Year: 2018, Volume and Issue: 13(1)

Published: April 30, 2018

In the mammalian cerebral cortex neurons are arranged in specific layers and form connections both within with other brain regions, thus forming a complex mesh of specialized synaptic comprising distinct circuits. The correct establishment these during development is crucial for proper function brain. Astrocytes, major type glial cell, important regulators synapse formation development. While neurogenesis precedes astrogenesis cortex, neuronal synapses only begin to after astrocytes have been generated, concurrent branching process elaboration. Here we provide combined overview developmental processes circuit rodent emphasizing timeline astrocytic maturation. We further discuss role at synapse, focusing on astrocyte-synapse contact synapse-related proteins promoting cortical

Language: Английский

Citations

340
Crosstalk Between Astrocytes and Microglia: An Overview DOI Creative Commons
Agata Matejuk, Richard M. Ransohoff

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: July 16, 2020

Based on discoveries enabled by new technologies and analyzed using novel computational tools, neuroscience can be re-conceived in terms of information exchange dense networks intercellular connections rather than the context individual populations, such as glia or neurons.. Cross-talk between neurons microglia astrocytes are has been addressed, however, manner which non-neuronal cells communicate interact remains less well understood. We review this intriguing crosstalk among CNS cells, focusing how it contributes to brain development two neurodegenerative diseases: Alzheimer disease GRN-FTLD most prevalent tumor, astrocytoma. The goal studying these communications is promote our ability combat incurable neurological disorders.

Language: Английский

Citations

330
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

315
Astrocyte morphology: Diversity, plasticity, and role in neurological diseases DOI Creative Commons
Bin Zhou, Yunxia Zuo, Ruotian Jiang

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2019, Volume and Issue: 25(6), P. 665 - 673

Published: March 30, 2019

Summary Astrocytes are the most abundant glial cells in central nervous system (CNS) and participate synaptic, circuit, behavioral functions. The well‐developed protoplasmic astrocytes contain numerous processes forming well‐delineated bushy territories that overlap by as little 5% at their boundaries. This highly complex morphology, with up to approximately 80% of cell's membrane constituted fine dimensions on tens nanometer scale high surface area volume ratios, comes contact synapses, blood vessels, other cells. Recent progress is challenging conventional view morphologically homogeneous throughout brain; instead, they display circuit‐ region‐specific morphological diversity may contribute heterogeneous astrocyte‐neuron spatiotemporal interplay different brain areas. Further, structure found be plastic activity‐dependent. We beginning understand how astrocyte structural plasticity contributes change/loss traditionally known a hallmark for reactive astrogliosis, common pathological feature many neurological disorders. However, recent data suggest deficits preceding astrogliosis drive disease progression. review summarizes advances diversity, plasticity, disease‐related deficits.

Language: Английский

Citations

312
Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS DOI Creative Commons

Yuqin Men,

Julia Yelick, Shijie Jin

et al.

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Sept. 12, 2019

Abstract Astroglia play active and diverse roles in modulating neuronal/synaptic functions the CNS. How these astroglial are regulated, especially by neuronal signals, remains largely unknown. Exosomes, a major type of extracellular vesicles (EVs) that originate from endosomal intraluminal (ILVs), have emerged as new intercellular communication process. By generating cell-type-specific ILVs/exosome reporter (CD63-GFP f/f ) mice immuno-EM/confocal image analysis, we found CD63-GFP + ILVs primarily localized soma dendrites, but not axonal terminals vitro vivo. Secreted exosomes contain subset microRNAs (miRs) is distinct miR profile neurons. These miRs, neuron-specific miR-124-3p, potentially internalized into astrocytes. MiR-124-3p further up-regulates predominant glutamate transporter GLT1 suppressing GLT1-inhibiting miRs. Our findings suggest previously undescribed exosomal miR-mediated genetic regulation astrocyte functions, opening frontier understanding CNS communication.

Language: Английский

Citations

284
Astrocytes and oligodendrocytes undergo subtype-specific transcriptional changes in Alzheimer’s disease DOI Creative Commons
Jessica S. Sadick, Michael R. O’Dea, Philip Hasel

et al.

Neuron, Journal Year: 2022, Volume and Issue: 110(11), P. 1788 - 1805.e10

Published: April 4, 2022

Language: Английский

Citations

258