A survey of human brain transcriptome diversity at the single cell level
Spyros Darmanis,Steven A. Sloan,Ye Zhang,Martin Enge,Christine Caneda,Lawrence M. Shuer,Melanie Hayden Gephart,Ben A. Barres,Stephen R. Quake +8 more
TLDR
The first, to the authors' knowledge, single cell whole transcriptome analysis of human adult cortical samples is described, establishing an experimental and analytical framework with which the complexity of the human brain can be dissected on the single cell level.Abstract:
The human brain is a tissue of vast complexity in terms of the cell types it comprises. Conventional approaches to classifying cell types in the human brain at single cell resolution have been limited to exploring relatively few markers and therefore have provided a limited molecular characterization of any given cell type. We used single cell RNA sequencing on 466 cells to capture the cellular complexity of the adult and fetal human brain at a whole transcriptome level. Healthy adult temporal lobe tissue was obtained during surgical procedures where otherwise normal tissue was removed to gain access to deeper hippocampal pathology in patients with medical refractory seizures. We were able to classify individual cells into all of the major neuronal, glial, and vascular cell types in the brain. We were able to divide neurons into individual communities and show that these communities preserve the categorization of interneuron subtypes that is typically observed with the use of classic interneuron markers. We then used single cell RNA sequencing on fetal human cortical neurons to identify genes that are differentially expressed between fetal and adult neurons and those genes that display an expression gradient that reflects the transition between replicating and quiescent fetal neuronal populations. Finally, we observed the expression of major histocompatibility complex type I genes in a subset of adult neurons, but not fetal neurons. The work presented here demonstrates the applicability of single cell RNA sequencing on the study of the adult human brain and constitutes a first step toward a comprehensive cellular atlas of the human brain.read more
Citations
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SCENIC: single-cell regulatory network inference and clustering.
Sara Aibar,Carmen Bravo González-Blas,Thomas Moerman,Vân Anh Huynh-Thu,Hana Imrichova,Gert Hulselmans,Florian Rambow,Jean-Christophe Marine,Pierre Geurts,Jan Aerts,Joost van den Oord,Zeynep Kalender Atak,Jasper Wouters,Stein Aerts +13 more
TL;DR: On a compendium of single-cell data from tumors and brain, it is demonstrated that cis-regulatory analysis can be exploited to guide the identification of transcription factors and cell states.
Journal ArticleDOI
Single-cell transcriptomics of 20 mouse organs creates a "Tabula Muris"
Overall coordination,Logistical coordination,Library preparation,Cell type annotation,Principal investigators +4 more
TL;DR: A compendium of single-cell transcriptomic data from the model organism Mus musculus that comprises more than 100,000 cells from 20 organs and tissues is presented, representing a new resource for cell biology and enabling the direct and controlled comparison of gene expression in cell types that are shared between tissues.
Journal ArticleDOI
The Human Cell Atlas
Aviv Regev,Aviv Regev,Aviv Regev,Sarah A. Teichmann,Sarah A. Teichmann,Sarah A. Teichmann,Eric S. Lander,Eric S. Lander,Eric S. Lander,Ido Amit,Christophe Benoist,Ewan Birney,Bernd Bodenmiller,Bernd Bodenmiller,Peter J. Campbell,Peter J. Campbell,Piero Carninci,Menna R. Clatworthy,Hans Clevers,Bart Deplancke,Ian Dunham,James Eberwine,Roland Eils,Roland Eils,Wolfgang Enard,Andrew Farmer,Lars Fugger,Berthold Göttgens,Nir Hacohen,Nir Hacohen,Muzlifah Haniffa,Martin Hemberg,Seung K. Kim,Paul Klenerman,Paul Klenerman,Arnold R. Kriegstein,Ed S. Lein,Sten Linnarsson,Emma Lundberg,Emma Lundberg,Joakim Lundeberg,Partha P. Majumder,John C. Marioni,John C. Marioni,John C. Marioni,Miriam Merad,Musa M. Mhlanga,Martijn C. Nawijn,Mihai G. Netea,Garry P. Nolan,Dana Pe'er,Anthony Phillipakis,Chris P. Ponting,Stephen R. Quake,Wolf Reik,Wolf Reik,Wolf Reik,Orit Rozenblatt-Rosen,Joshua R. Sanes,Rahul Satija,Ton N. Schumacher,Alex K. Shalek,Alex K. Shalek,Alex K. Shalek,Ehud Shapiro,Padmanee Sharma,Jay W. Shin,Oliver Stegle,Michael R. Stratton,Michael J. T. Stubbington,Fabian J. Theis,Matthias Uhlen,Matthias Uhlen,Alexander van Oudenaarden,Allon Wagner,Fiona M. Watt,Jonathan S. Weissman,Barbara J. Wold,Ramnik J. Xavier,Nir Yosef,Nir Yosef,Human Cell Atlas Meeting Participants +81 more
TL;DR: An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease.
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The Cellular Phase of Alzheimer’s Disease
TL;DR: Evidence supporting a long, complex cellular phase consisting of feedback and feedforward responses of astrocytes, microglia, and vasculature is reviewed.
Journal ArticleDOI
An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma
Cyril Neftel,Julie Laffy,Mariella G. Filbin,Toshiro Hara,Marni E. Shore,Marni E. Shore,Gilbert J. Rahme,Gilbert J. Rahme,Alyssa R. Richman,Alyssa R. Richman,Dana Silverbush,Dana Silverbush,McKenzie Shaw,Christine M. Hebert,Christine M. Hebert,John M. DeWitt,John M. DeWitt,Simon Gritsch,Simon Gritsch,Elizabeth M. Perez,Elizabeth M. Perez,L. Nicolas Gonzalez Castro,Xiaoyang Lan,Xiaoyang Lan,Nicholas Druck,Christopher Rodman,Danielle Dionne,Alexander Kaplan,Mia Bertalan,Julia L. Small,Kristine Pelton,Sarah Becker,Dennis M. Bonal,Quang-Dé Nguyen,Rachel L. Servis,Jeremy M. Fung,Ravindra Mylvaganam,Lisa Mayr,Johannes Gojo,Christine Haberler,René Geyeregger,Thomas Czech,Irene Slavc,Brian V. Nahed,William T. Curry,Bob S. Carter,Hiroaki Wakimoto,Priscilla K. Brastianos,Tracy T. Batchelor,Anat Stemmer-Rachamimov,Maria Martinez-Lage,Matthew P. Frosch,Ivan Stamenkovic,Nicolo Riggi,Esther Rheinbay,Esther Rheinbay,Michelle Monje,Orit Rozenblatt-Rosen,Daniel P. Cahill,Anoop P. Patel,Tony Hunter,Inder M. Verma,Keith L. Ligon,Keith L. Ligon,David N. Louis,Aviv Regev,Aviv Regev,Bradley E. Bernstein,Bradley E. Bernstein,Itay Tirosh,Mario L. Suvà,Mario L. Suvà +71 more
TL;DR: It is found that malignant cells in glioblastoma exist in four main cellular states that recapitulate distinct neural cell types, are influenced by the tumor microenvironment, and exhibit plasticity.
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Three groups of interneurons account for nearly 100% of neocortical GABAergic neurons
TL;DR: The universal modulation of these neurons by serotonin and acetylcholine via ionotropic receptors suggests that they might be involved in shaping cortical circuits during specific brain states andbehavioral contexts.
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