Spatial Transcriptomics: Molecular Maps of the Mammalian Brain

2021 ◽  
Vol 44 (1) ◽  
Author(s):  
Cantin Ortiz ◽  
Marie Carlén ◽  
Konstantinos Meletis
Keyword(s):  
Nervous System ◽  
Molecular Classification ◽  
Cell Types ◽  
Brain Regions ◽  
Mammalian Brain ◽  
Annual Review ◽  
Publication Date ◽  
Common Reference ◽  
Tissue Organization ◽  
Definition Of

Maps of the nervous system inspire experiments and theories in neuroscience. Advances in molecular biology over the past decades have revolutionized the definition of cell and tissue identity. Spatial transcriptomics has opened up a new era in neuroanatomy, where the unsupervised and unbiased exploration of the molecular signatures of tissue organization will give rise to a new generation of brain maps. We propose that the molecular classification of brain regions on the basis of their gene expression profile can circumvent subjective neuroanatomical definitions and produce common reference frameworks that can incorporate cell types, connectivity, activity, and other modalities. Here we review the technological and conceptual advances made possible by spatial transcriptomics in the context of advancing neuroanatomy and discuss how molecular neuroanatomy can redefine mapping of the nervous system. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Integrated Patterning Programs During Drosophila Development Generate the Diversity of Neurons and Control Their Mature Properties

2021 ◽  
Vol 44 (1) ◽  
Author(s):  
Anthony M. Rossi ◽  
Shadi Jafari ◽  
Claude Desplan
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Neural Stem Cells ◽  
Cell Types ◽  
Annual Review ◽  
Publication Date ◽  
Temporal Patterning ◽  
Long Time ◽  
Neuronal Types ◽  
And Control

During the approximately 5 days of Drosophila neurogenesis (late embryogenesis to the beginning of pupation), a limited number of neural stem cells produce approximately 200,000 neurons comprising hundreds of cell types. To build a functional nervous system, neuronal types need to be produced in the proper places, appropriate numbers, and correct times. We discuss how neural stem cells (neuroblasts) obtain so-called area codes for their positions in the nervous system (spatial patterning) and how they keep time to sequentially produce neurons with unique fates (temporal patterning). We focus on specific examples that demonstrate how a relatively simple patterning system (Notch) can be used reiteratively to generate different neuronal types. We also speculate on how different modes of temporal patterning that operate over short versus long time periods might be linked. We end by discussing how specification programs are integrated and lead to the terminal features of different neuronal types. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Seq Your Destiny: Neural Crest Fate Determination in the Genomic Era

2021 ◽  
Vol 55 (1) ◽  
Author(s):  
Shashank Gandhi ◽  
Marianne E. Bronner
Keyword(s):  
Nervous System ◽  
Neural Crest ◽  
Cell Lineage ◽  
Cell Types ◽  
The Body ◽  
Annual Review ◽  
Publication Date ◽  
Developmental Potential ◽  
Migratory Patterns ◽  
Modern Genomic

Neural crest stem/progenitor cells arise early during vertebrate embryogenesis at the border of the forming central nervous system. They subsequently migrate throughout the body, eventually differentiating into diverse cell types ranging from neurons and glia of the peripheral nervous system to bones of the face, portions of the heart, and pigmentation of the skin. Along the body axis, the neural crest is heterogeneous, with different subpopulations arising in the head, neck, trunk, and tail regions, each characterized by distinct migratory patterns and developmental potential. Modern genomic approaches like single-cell RNA- and ATAC-sequencing (seq) have greatly enhanced our understanding of cell lineage trajectories and gene regulatory circuitry underlying the developmental progression of neural crest cells. Here, we discuss how genomic approaches have provided new insights into old questions in neural crest biology by elucidating transcriptional and posttranscriptional mechanisms that govern neural crest formation and the establishment of axial level identity. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Challenges of Organoid Research

2022 ◽  
Vol 45 (1) ◽  
Author(s):  
Madeline G. Andrews ◽  
Arnold R. Kriegstein
Keyword(s):  
Human Brain ◽  
Neurological Diseases ◽  
3D Cell Culture ◽  
Cell Types ◽  
Annual Review ◽  
Publication Date ◽  
Human Brain Tissue ◽  
Scientific Advance ◽  
Tissue Organization ◽  
Genetic Features

Organoids are 3D cell culture systems derived from human pluripotent stem cells that contain tissue resident cell types and reflect features of early tissue organization. Neural organoids are a particularly innovative scientific advance given the lack of accessibility of developing human brain tissue and intractability of neurological diseases. Neural organoids have become an invaluable approach to model features of human brain development that are not well reflected in animal models. Organoids also hold promise for the study of atypical cellular, molecular, and genetic features that underscore neurological diseases. Additionally, organoids may provide a platform for testing therapeutics in human cells and are a potential source for cell replacement approaches to brain injury or disease. Despite the promising features of organoids, their broad utility is hampered by a variety of limitations, including lack of high-fidelity cell types, limited maturation, atypical physiology, and lack of arealization, features that may limit their reliability for certain applications. Expected final online publication date for the Annual Review of Neuroscience, Volume 45 is July 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Pathogenic Mechanisms Underlying Idiopathic Pulmonary Fibrosis

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Benjamin J. Moss ◽  
Stefan W. Ryter ◽  
Ivan O. Rosas
Keyword(s):  
Epithelial Cell ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Activation ◽  
Alveolar Epithelial Cell ◽  
Cell Types ◽  
Annual Review ◽  
Publication Date ◽  
Metabolic Dysfunction ◽  
Epithelial Repair

The pathogenesis of idiopathic pulmonary fibrosis (IPF) involves a complex interplay of cell types and signaling pathways. Recurrent alveolar epithelial cell (AEC) injury may occur in the context of predisposing factors (e.g., genetic, environmental, epigenetic, immunologic, and gerontologic), leading to metabolic dysfunction, senescence, aberrant epithelial cell activation, and dysregulated epithelial repair. The dysregulated epithelial cell interacts with mesenchymal, immune, and endothelial cells via multiple signaling mechanisms to trigger fibroblast and myofibroblast activation. Recent single-cell RNA sequencing studies of IPF lungs support the epithelial injury model. These studies have uncovered a novel type of AEC with characteristics of an aberrant basal cell, which may disrupt normal epithelial repair and propagate a profibrotic phenotype. Here, we review the pathogenesis of IPF in the context of novel bioinformatics tools as strategies to discover pathways of disease, cell-specific mechanisms, and cell-cell interactions that propagate the profibrotic niche. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Recent Research on the Archaeology of War and Violence

2021 ◽  
Vol 50 (1) ◽  
Author(s):  
Andrew K. Scherer
Keyword(s):  
State Formation ◽  
Online Publication ◽  
General Trend ◽  
Annual Review ◽  
Publication Date ◽  
Modern Times ◽  
The Past ◽  
Definition Of ◽  
Consequences Of Violence

The mid-1990s through the first decade of the new millennium marked an increase in publications pertaining to war and violence in the ancient past. This review considers how scholars of the past decade have responded to that work. The emerging consensus is that war and violence were endemic to all societies studied by archaeologists, and yet the frequency, intensity, causes, and consequences of violence were highly variable for reasons that defy simplistic explanation. The general trend has been toward archaeologies of war and violence that focus on understanding the nuances of particular places and historical moments. Nevertheless, archaeologists continue to grapple with grand narratives of war, such as the proposition that violence has decreased from ancient to modern times and the role of war and violence in state formation and collapse. Recent research also draws attention to a more expansive definition of violence. Expected final online publication date for the Annual Review of Anthropology, Volume 50 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Aging of the Retina: Molecular and Metabolic Turbulences and Potential Interventions

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Laura Campello ◽  
Nivedita Singh ◽  
Jayshree Advani ◽  
Anupam K. Mondal ◽  
Ximena Corso-Diaz ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Cell Types ◽  
Lifestyle Changes ◽  
Annual Review ◽  
Past Century ◽  
Publication Date ◽  
Vision Science ◽  
Human Lifespan ◽  
Cellular Events ◽  
Age Related

Multifaceted and divergent manifestations across tissues and cell types have curtailed advances in deciphering the cellular events that accompany advanced age and contribute to morbidities and mortalities. Increase in human lifespan during the past century has heightened awareness of the need to prevent age-associated frailty of neuronal and sensory systems to allow a healthy and productive life. In this review, we discuss molecular and physiological attributes of aging of the retina, with a goal of understanding age-related impairment of visual function. We highlight the epigenome–metabolism nexus and proteostasis as key contributors to retinal aging and discuss lifestyle changes as potential modulators of retinal function. Finally, we deliberate promising intervention strategies for promoting healthy aging of the retina for improved vision. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

β-Arrestins as Important Regulators of Glucose and Energy Homeostasis

2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Sai P. Pydi ◽  
Luiz F. Barella ◽  
Lu Zhu ◽  
Jaroslawna Meister ◽  
Mario Rossi ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Cell Types ◽  
Mutant Mice ◽  
Whole Body ◽  
Annual Review ◽  
Publication Date ◽  
Cytoplasmic Proteins ◽  
New Findings ◽  
Novel Drugs ◽  
G Protein Coupled

β-Arrestin-1 and -2 (also known as arrestin-2 and -3, respectively) are ubiquitously expressed cytoplasmic proteins that dampen signaling through G protein–coupled receptors. However, β-arrestins can also act as signaling molecules in their own right. To investigate the potential metabolic roles of the two β-arrestins in modulating glucose and energy homeostasis, recent studies analyzed mutant mice that lacked or overexpressed β-arrestin-1 and/or -2 in distinct, metabolically important cell types. Metabolic analysis of these mutant mice clearly demonstrated that both β-arrestins play key roles in regulating the function of most of these cell types, resulting in striking changes in whole-body glucose and/or energy homeostasis. These studies also revealed that β-arrestin-1 and -2, though structurally closely related, clearly differ in their metabolic roles under physiological and pathophysiological conditions. These new findings should guide the development of novel drugs for the treatment of various metabolic disorders, including type 2 diabetes and obesity. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Astrocytes and Behavior

2021 ◽  
Vol 44 (1) ◽  
Author(s):  
Paulo Kofuji ◽  
Alfonso Araque
Keyword(s):  
Glial Cells ◽  
Neuronal Activity ◽  
Animal Behavior ◽  
Paradigm Shift ◽  
Mammalian Brain ◽  
Annual Review ◽  
Publication Date ◽  
Brain Circuits ◽  
Intracellular Ca ◽  
And Behavior

Animal behavior was classically considered to be determined exclusively by neuronal activity, whereas surrounding glial cells such as astrocytes played only supportive roles. However, astrocytes are as numerous as neurons in the mammalian brain, and current findings indicate a chemically based dialog between astrocytes and neurons. Activation of astrocytes by synaptically released neurotransmitters converges on regulating intracellular Ca2+ in astrocytes, which then can regulate the efficacy of near and distant tripartite synapses at diverse timescales through gliotransmitter release. Here, we discuss recent evidence on how diverse behaviors are impacted by this dialog. These recent findings support a paradigm shift in neuroscience, in which animal behavior does not result exclusively from neuronal activity but from the coordinated activity of both astrocytes and neurons. Decoding how astrocytes and neurons interact with each other in various brain circuits will be fundamental to fully understanding how behaviors originate and become dysregulated in disease. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Generating and Using Transcriptomically Based Retinal Cell Atlases

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Karthik Shekhar ◽  
Joshua R. Sanes
Keyword(s):  
Expression Patterns ◽  
Retinal Disease ◽  
Cell Types ◽  
Retinal Cell ◽  
Annual Review ◽  
Publication Date ◽  
Vertebrate Species ◽  
Retinal Cells ◽  
Vision Science ◽  
The Brain

It has been known for over a century that the basic organization of the retina is conserved across vertebrates. It has been equally clear that retinal cells can be classified into numerous types, but only recently have methods been devised to explore this diversity in unbiased, scalable, and comprehensive ways. Advances in high-throughput single-cell RNA-sequencing (scRNA-seq) have played a pivotal role in this effort. In this article, we outline the experimental and computational components of scRNA-seq and review studies that have used them to generate retinal atlases of cell types in several vertebrate species. These atlases have enabled studies of retinal development, responses of retinal cells to injury, expression patterns of genes implicated in retinal disease, and the evolution of cell types. Recently, the inquiry has expanded to include the entire eye and visual centers in the brain. These studies have enhanced our understanding of retinal function and dysfunction and provided tools and insights for exploring neural diversity throughout the brain. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Metabolic Gatekeepers of Pathological B Cell Activation

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Teresa Sadras ◽  
Lai N. Chan ◽  
Gang Xiao ◽  
Markus Müschen
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Cell Types ◽  
Cell Receptor ◽  
Annual Review ◽  
Publication Date ◽  
B Cell Activation ◽  
Dna Double Strand Breaks ◽  
Increased Risk

Unlike other cell types, B cells undergo multiple rounds of V(D)J recombination and hypermutation to evolve high-affinity antibodies. Reflecting high frequencies of DNA double-strand breaks, adaptive immune protection by B cells comes with an increased risk of malignant transformation. In addition, the vast majority of newly generated B cells express an autoreactive B cell receptor (BCR). Thus, B cells are under intense selective pressure to remove autoreactive and premalignant clones. Despite stringent negative selection, B cells frequently give rise to autoimmune disease and B cell malignancies. In this review, we discuss mechanisms that we term metabolic gatekeepers to eliminate pathogenic B cell clones on the basis of energy depletion. Chronic activation signals from autoreactive BCRs or transforming oncogenes increase energy demands in autoreactive and premalignant B cells. Thus, metabolic gatekeepers limit energy supply to levels that are insufficient to fuel either a transforming oncogene or hyperactive signaling from an autoreactive BCR. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 16 is February 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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