Dorothy P Schafer, Beth Stevens, Mariko L Bennett, Frederick C Bennett
{"title":"Role of Microglia in Central Nervous System Development and Plasticity.","authors":"Dorothy P Schafer, Beth Stevens, Mariko L Bennett, Frederick C Bennett","doi":"10.1101/cshperspect.a041810","DOIUrl":"https://doi.org/10.1101/cshperspect.a041810","url":null,"abstract":"<p><p>The nervous system comprises a remarkably diverse and complex network of cell types, which must communicate with one another with speed, reliability, and precision. Thus, the developmental patterning and maintenance of these cell populations and their connections with one another pose a rather formidable task. Emerging data implicate microglia, the resident myeloid-derived cells of the central nervous system (CNS), in spatial patterning and synaptic wiring throughout the healthy, developing, and adult CNS. Importantly, new tools to specifically manipulate microglia function have revealed that these cellular functions translate, on a systems level, to effects on overall behavior. In this review, we give a historical perspective of work to identify microglia function in the healthy CNS, and highlight exciting new discoveries about their contributions to CNS development, maintenance, and plasticity.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gerard Crowley, David Attwell, Hemali Phatnani, Harald Sontheimer, Soyon Hong
{"title":"Glia in Neurodegenerative Disease","authors":"Gerard Crowley, David Attwell, Hemali Phatnani, Harald Sontheimer, Soyon Hong","doi":"10.1101/cshperspect.a041375","DOIUrl":"https://doi.org/10.1101/cshperspect.a041375","url":null,"abstract":"It is becoming increasingly clear that the dominant, century-old neurocentric view of neurodegeneration is insufficient to explain why certain neurons degenerate, in particular with aging. Genetic studies in patient populations as well as mechanistic and functional studies in animal models altogether implicate nonneuronal cells, especially glia, to play more than bystander roles in neurodegeneration. Throughout the life span, neuronal function and homeostasis are modulated by glia, the functions of which become even more critical with aging. This review highlights key emerging concepts of the role of glia in neurodegeneration.","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":"30 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142253966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Glial Malignancies","authors":"Suzanne J. Baker, Hui Zong, Michelle Monje","doi":"10.1101/cshperspect.a041373","DOIUrl":"https://doi.org/10.1101/cshperspect.a041373","url":null,"abstract":"Gliomas comprise a diverse spectrum of related tumor subtypes with varying biological and molecular features and clinical outcomes. Advances in detailed genetic and epigenetic characterizations along with an appreciation that subtypes associated with developmental origins, including brain location and patient age, have shifted glioma classification from the historical reliance on histopathological features to updated categories incorporating molecular signatures and spatiotemporal incidence. Within a subtype, individual gliomas show cellular heterogeneity, generally containing subpopulations resembling different types of normal glial and progenitor cells. In addition to tumor-autonomous mechanisms of aberrant growth regulation driven by genetic mutations and signaling between tumor cells, interactions with the tumor microenvironment, including neurons, astrocytes, oligodendrocyte precursor cells, and the immune microenvironment play important roles in driving glioma growth and influencing response to treatment. The emerging understanding of the complex contributions of normal brain to glioma growth represents new opportunities for therapeutic advances.","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":"10 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142253968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Biology of Glia","authors":"Beth Stevens, Kelly R. Monk, Marc R. Freeman","doi":"10.1101/cshperspect.a041809","DOIUrl":"https://doi.org/10.1101/cshperspect.a041809","url":null,"abstract":"Glial cells play critical roles in the nervous system. Rather than being passive support cells as long thought, they are highly active participants. Recent work has shed new light on their many functions, include regulation of synapse formation and function, control of neural circuits, and neuro-immune interactions. It is also shedding light on the part they play in neurodegenerative diseases and malignancies such as glioma, as well as the process of axonal regeneration and CNS repair.","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":"117 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142253967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Artificial Intelligence Learns Protein Prediction.","authors":"Michael Heinzinger, Burkhard Rost","doi":"10.1101/cshperspect.a041458","DOIUrl":"10.1101/cshperspect.a041458","url":null,"abstract":"<p><p>From <i>AlphaGO</i> over <i>StableDiffusion</i> to <i>ChatGPT</i>, the recent decade of exponential advances in artificial intelligence (AI) has been altering life. In parallel, advances in computational biology are beginning to decode the language of life: <i>AlphaFold2</i> leaped forward in protein structure prediction, and protein language models (pLMs) replaced expertise and evolutionary information from multiple sequence alignments with information learned from reoccurring patterns in databases of billions of proteins without experimental annotations other than the amino acid sequences. None of those tools could have been developed 10 years ago; all will increase the wealth of experimental data and speed up the cycle from idea to proof. AI is affecting molecular and medical biology at giant steps, and the most important might be the leap toward more powerful protein design.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ken A Thompson, Yaniv Brandvain, Jenn M Coughlan, Kira E Delmore, Hannah Justen, Catherine R Linnen, Daniel Ortiz-Barrientos, Catherine A Rushworth, Hilde Schneemann, Molly Schumer, Rike Stelkens
{"title":"The Ecology of Hybrid Incompatibilities.","authors":"Ken A Thompson, Yaniv Brandvain, Jenn M Coughlan, Kira E Delmore, Hannah Justen, Catherine R Linnen, Daniel Ortiz-Barrientos, Catherine A Rushworth, Hilde Schneemann, Molly Schumer, Rike Stelkens","doi":"10.1101/cshperspect.a041440","DOIUrl":"10.1101/cshperspect.a041440","url":null,"abstract":"<p><p>Ecologically mediated selection against hybrids, caused by hybrid phenotypes fitting poorly into available niches, is typically viewed as distinct from selection caused by epistatic Dobzhansky-Muller hybrid incompatibilities. Here, we show how selection against transgressive phenotypes in hybrids manifests as incompatibility. After outlining our logic, we summarize current approaches for studying ecology-based selection on hybrids. We then quantitatively review QTL-mapping studies and find traits differing between parent taxa are typically polygenic. Next, we describe how verbal models of selection on hybrids translate to phenotypic and genetic fitness landscapes, highlighting emerging approaches for detecting polygenic incompatibilities. Finally, in a synthesis of published data, we report that trait transgression-and thus possibly extrinsic hybrid incompatibility in hybrids-escalates with the phenotypic divergence between parents. We discuss conceptual implications and conclude that studying the ecological basis of hybrid incompatibility will facilitate new discoveries about mechanisms of speciation.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leon C.D. Smyth, Natalie Beschorner, Maiken Nedergaard, Jonathan Kipnis
{"title":"Cellular Contributions to Glymphatic and Lymphatic Waste Clearance in the Brain","authors":"Leon C.D. Smyth, Natalie Beschorner, Maiken Nedergaard, Jonathan Kipnis","doi":"10.1101/cshperspect.a041370","DOIUrl":"https://doi.org/10.1101/cshperspect.a041370","url":null,"abstract":"Cerebrospinal fluid (CSF) bathes and cushions the brain; however, it also serves a major role in the clearance of metabolic wastes and in the distribution of glucose, lipids, and amino acids. Unlike every other organ in the body, the brain parenchyma lacks a traditional lymphatic system to drain fluids and central nervous system (CNS) antigens. It was historically assumed that all brain wastes were removed by endogenous processing, such as phagocytosis and autophagy, while excess fluids drained directly into the blood. However, the twin discoveries of the glial-lymphatic (glymphatic) system and meningeal lymphatics have transformed our understanding of brain waste clearance. The glymphatic system describes the movement of fluids through the subarachnoid space (SAS), the influx along periarterial spaces into the brain parenchyma, and the ultimate efflux back into the SAS along perivenous spaces where it comes into direct contact with the meningeal lymphatics. The dura mater of the meninges contains a bona fide lymphatic network that can drain CSF that has entered the dura. Together, these pathways provide insights into the clearance of molecules and fluids from the brain, and show that the CNS is physically connected to the adaptive immune system. Here, we outline the glymphatic and lymphatic systems, and describe the cellular components that are important to their function.","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":"32 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stefano Schiaffino, Francesco Chemello, Carlo Reggiani
{"title":"The Diversity of Skeletal Muscle Fiber Types","authors":"Stefano Schiaffino, Francesco Chemello, Carlo Reggiani","doi":"10.1101/cshperspect.a041477","DOIUrl":"https://doi.org/10.1101/cshperspect.a041477","url":null,"abstract":"The widespread presence of slow-red and fast-white muscles in all vertebrates supports the evolutionary advantage of having two types of motors available for animal movement—a slow economical motor used for most activities, and a fast energetically costly motor used for rapid movements and emergency actions, and actions that require a lot of force. Skeletal muscles are composed of multiple fiber types whose structural and functional properties have only in part been characterized. Further progress in this field is mainly occurring along two directions: Multiomics approaches are providing a global picture of the molecular composition of muscle fibers up to the single fiber and single nucleus level. Signaling studies are identifying many transcription factors and pathways controlling fiber-type specification. These new data should now be integrated into a wider whole-body context by defining the matching between muscle fiber and motor neuron heterogeneity in the neuromuscular system, as well as the relevance of muscle fiber types in systemic homeostatic functions, including metabolism and thermogenesis.","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":"74 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anjana Sevagamoorthy, Adeline Vanderver, Jamie L. Fraser, Jennifer Orthmann-Murphy
{"title":"Glial Origins of Inherited White Matter Disorders","authors":"Anjana Sevagamoorthy, Adeline Vanderver, Jamie L. Fraser, Jennifer Orthmann-Murphy","doi":"10.1101/cshperspect.a041457","DOIUrl":"https://doi.org/10.1101/cshperspect.a041457","url":null,"abstract":"Inherited white matter disorders (IWMDs) are a phenotypically and genotypically heterogeneous group of disorders affecting the central nervous system (CNS) with or without peripheral neuropathy. They are classified either as leukodystrophies (LDs), with primary glial abnormalities, or genetic leukoencephalopathies (gLEs), where other CNS cells are involved. As a group, these disorders are common, with an incidence of 1 in 7500 births. However, IWMDs often go undiagnosed or suffer delayed or misdiagnosis due to their heterogeneous presentation. Many of these disorders present with lethal secondary manifestations that can be prevented through early disease recognition, periodic surveillance, and preventative management. Emerging therapeutics, including gene therapy trials for metachromatic leukodystrophy (MLD) and adrenoleukodystrophy (ALD), suggest disease progression may be slowed or even prevented if treated early. Therapies for IWMDs that target glial cells or the peripheral immune system may provide novel insights for treating acquired disorders of white matter.","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":"40 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anais Franco-Romero, Marco Sandri, Stefano Schiaffino
{"title":"Autophagy in Skeletal Muscle","authors":"Anais Franco-Romero, Marco Sandri, Stefano Schiaffino","doi":"10.1101/cshperspect.a041565","DOIUrl":"https://doi.org/10.1101/cshperspect.a041565","url":null,"abstract":"Skeletal muscle fibers possess, like all cells of our body, an evolutionary conserved autophagy machinery, which allows them to segregate unfolded proteins and damaged organelles within autophagosomes, and to induce fusion of autophagosomes with lysosomes, leading to degradation of those altered cell constituents. This process may be selective for specific cell components, as in the case of glycogen (glycophagy) or organelles, as with mitochondria (mitophagy). The autophagic flux is activated by fasting, and contributes with the proteasome to provide the organism with amino acids required for survival. Autophagy is also essential for the normal turnover of muscle proteins and organelles, as shown by the degenerative changes induced by genetic block of the autophagic mechanism, and in several myopathies. Autophagy is enhanced in muscle by exercise and impaired during aging, suggesting that aging-dependent muscle dysfunction could be delayed by boosting autophagy.","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":"1 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}