The single-cell transcriptional landscape of mammalian organogenesis
Junyue Cao,Malte Spielmann,Xiaojie Qiu,Xingfan Huang,Daniel M. Ibrahim,Daniel M. Ibrahim,Andrew J. Hill,Fan Zhang,Stefan Mundlos,Stefan Mundlos,Lena Christiansen,Frank J. Steemers,Cole Trapnell,Jay Shendure +13 more
TLDR
A cell atlas of mouse organogenesis provides a global view of developmental processes occurring during this critical period, including focused analyses of the apical ectodermal ridge, limb mesenchyme and skeletal muscle.Abstract:
Mammalian organogenesis is a remarkable process. Within a short timeframe, the cells of the three germ layers transform into an embryo that includes most of the major internal and external organs. Here we investigate the transcriptional dynamics of mouse organogenesis at single-cell resolution. Using single-cell combinatorial indexing, we profiled the transcriptomes of around 2 million cells derived from 61 embryos staged between 9.5 and 13.5 days of gestation, in a single experiment. The resulting ‘mouse organogenesis cell atlas’ (MOCA) provides a global view of developmental processes during this critical window. We use Monocle 3 to identify hundreds of cell types and 56 trajectories, many of which are detected only because of the depth of cellular coverage, and collectively define thousands of corresponding marker genes. We explore the dynamics of gene expression within cell types and trajectories over time, including focused analyses of the apical ectodermal ridge, limb mesenchyme and skeletal muscle. Data from single-cell combinatorial-indexing RNA-sequencing analysis of 2 million cells from mouse embryos between embryonic days 9.5 and 13.5 are compiled in a cell atlas of mouse organogenesis, which provides a global view of developmental processes occurring during this critical period.read more
Citations
More filters
Journal ArticleDOI
Integrated analysis of multimodal single-cell data
Yuhan Hao,Stephanie Hao,Erica Andersen-Nissen,William M. Mauck,Shiwei Zheng,Andrew Butler,Maddie Jane Lee,Aaron J. Wilk,Charlotte A. Darby,Michael Zager,Paul Hoffman,Marlon Stoeckius,Efthymia Papalexi,Eleni P. Mimitou,Jaison Jain,Avi Srivastava,Tim Stuart,Lamar M. Fleming,Bertrand Z. Yeung,Angela J. Rogers,Juliana M. McElrath,Catherine A. Blish,Raphael Gottardo,Peter Smibert,Rahul Satija +24 more
TL;DR: Weighted-nearest neighbor analysis as mentioned in this paper is an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities.
Journal ArticleDOI
COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis.
Robert Lorenz Chua,Soeren Lukassen,Saskia Trump,Bianca P Hennig,Daniel Wendisch,Fabian Pott,Olivia Debnath,Loreen Thürmann,Florian Kurth,Florian Kurth,Maria Theresa Völker,Julia Kazmierski,Bernd Timmermann,Sven Twardziok,Stefan Schneider,Felix Machleidt,Holger Müller-Redetzky,Melanie Maier,Alexander Krannich,Sein Schmidt,Felix Balzer,Johannes Liebig,Jennifer Loske,Norbert Suttorp,Jürgen Eils,Naveed Ishaque,Uwe G. Liebert,Christof von Kalle,Andreas C. Hocke,Martin Witzenrath,Christine Goffinet,Christian Drosten,Sven Laudi,Irina Lehmann,Christian Conrad,Leif E. Sander,Roland Eils,Roland Eils +37 more
TL;DR: The data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19, which likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure.
Journal ArticleDOI
SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells.
Soeren Lukassen,Robert Lorenz Chua,Timo Trefzer,Nicolas Kahn,Marc A. Schneider,Thomas Muley,Hauke Winter,Michael Meister,Carmen Veith,Agnes W. Boots,Bianca P Hennig,Michael Kreuter,Christian Conrad,Roland Eils,Roland Eils +14 more
TL;DR: This work investigates ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue and in cells derived from subsegmental bronchial branches by single nuclei and single cell RNA sequencing, suggesting increased vulnerability for SARS‐CoV‐2 infection.
Journal ArticleDOI
Eleven grand challenges in single-cell data science
David Lähnemann,David Lähnemann,Johannes Köster,Johannes Köster,Ewa Szczurek,Davis J. McCarthy,Davis J. McCarthy,Stephanie C. Hicks,Mark D. Robinson,Catalina A. Vallejos,Catalina A. Vallejos,Kieran R Campbell,Kieran R Campbell,Niko Beerenwinkel,Niko Beerenwinkel,Ahmed Mahfouz,Ahmed Mahfouz,Luca Pinello,Luca Pinello,Pavel Skums,Alexandros Stamatakis,Alexandros Stamatakis,Camille Stephan Otto Attolini,Samuel Aparicio,Samuel Aparicio,Jasmijn A. Baaijens,Marleen Balvert,Marleen Balvert,Buys de Barbanson,Antonio Cappuccio,Giacomo Corleone,Bas E. Dutilh,Bas E. Dutilh,Maria Florescu,Victor Guryev,Rens Holmer,Katharina Jahn,Katharina Jahn,Thamar Jessurun Lobo,Emma M. Keizer,Indu Khatri,Szymon M. Kielbasa,Jan O. Korbel,Alexey M. Kozlov,Tzu Hao Kuo,Boudewijn P. F. Lelieveldt,Boudewijn P. F. Lelieveldt,Ion I. Mandoiu,John C. Marioni,John C. Marioni,John C. Marioni,Tobias Marschall,Tobias Marschall,Felix Mölder,Amir Niknejad,Lukasz Raczkowski,Marcel J. T. Reinders,Marcel J. T. Reinders,Jeroen de Ridder,Antoine-Emmanuel Saliba,Antonios Somarakis,Oliver Stegle,Oliver Stegle,Fabian J. Theis,Huan Yang,Alexander Zelikovsky,Alexander Zelikovsky,Alice C. McHardy,Benjamin J. Raphael,Sohrab P. Shah,Alexander Schönhuth,Alexander Schönhuth +71 more
TL;DR: This compendium is for established researchers, newcomers, and students alike, highlighting interesting and rewarding problems for the coming years in single-cell data science.
Journal ArticleDOI
Construction of a human cell landscape at single-cell level.
Xiaoping Han,Ziming Zhou,Lijiang Fei,Huiyu Sun,Renying Wang,Yao Chen,Haide Chen,Jingjing Wang,Huanna Tang,Wenhao Ge,Yincong Zhou,Fang Ye,Mengmeng Jiang,Junqing Wu,Yanyu Xiao,Xiaoning Jia,Tingyue Zhang,Xiaojie Ma,Qi Zhang,Xueli Bai,Shujing Lai,Chengxuan Yu,Lijun Zhu,Rui Lin,Yuchi Gao,Min Wang,Yiqing Wu,Jianming Zhang,Renya Zhan,Saiyong Zhu,Hailan Hu,Changchun Wang,Ming Chen,He Huang,Tingbo Liang,Jianghua Chen,Weilin Wang,Dan Zhang,Guoji Guo +38 more
TL;DR: The results provide a useful resource for the study of human biology and find that stem and progenitor cells exhibit strong transcriptomic stochasticity, whereas differentiated cells are more distinct.
References
More filters
Journal ArticleDOI
STAR: ultrafast universal RNA-seq aligner
Alexander Dobin,Carrie A. Davis,Felix Schlesinger,Jorg Drenkow,Chris Zaleski,Sonali Jha,Philippe Batut,Mark Chaisson,Thomas R. Gingeras +8 more
TL;DR: The Spliced Transcripts Alignment to a Reference (STAR) software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure outperforms other aligners by a factor of >50 in mapping speed.
Journal ArticleDOI
HTSeq—a Python framework to work with high-throughput sequencing data
TL;DR: This work presents HTSeq, a Python library to facilitate the rapid development of custom scripts for high-throughput sequencing data analysis, and presents htseq-count, a tool developed with HTSequ that preprocesses RNA-Seq data for differential expression analysis by counting the overlap of reads with genes.
Journal ArticleDOI
Enrichr: a comprehensive gene set enrichment analysis web server 2016 update
Maxim V. Kuleshov,Matthew R. Jones,Andrew D. Rouillard,Nicolas F. Fernandez,Qiaonan Duan,Zichen Wang,Simon Koplev,Sherry L. Jenkins,Kathleen M. Jagodnik,Alexander Lachmann,Michael G. McDermott,Caroline D. Monteiro,Gregory W. Gundersen,Avi Ma'ayan +13 more
TL;DR: A significant update to one of the tools in this domain called Enrichr, a comprehensive resource for curated gene sets and a search engine that accumulates biological knowledge for further biological discoveries is presented.
Journal ArticleDOI
Notes on continuous stochastic phenomena.
TL;DR: Two problems arising in the two and three-dimensional cases of stochastic phenomena which are distributed in space of two or more dimensions are considered.
Posted Content
UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction
Leland McInnes,John Healy +1 more
TL;DR: The UMAP algorithm is competitive with t-SNE for visualization quality, and arguably preserves more of the global structure with superior run time performance.
Related Papers (5)
Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets
Evan Z. Macosko,Evan Z. Macosko,Anindita Basu,Anindita Basu,Rahul Satija,Rahul Satija,James Nemesh,James Nemesh,Karthik Shekhar,Melissa Goldman,Melissa Goldman,Itay Tirosh,Allison R. Bialas,Nolan Kamitaki,Nolan Kamitaki,Emily M. Martersteck,John J. Trombetta,David A. Weitz,Joshua R. Sanes,Alex K. Shalek,Alex K. Shalek,Alex K. Shalek,Aviv Regev,Aviv Regev,Aviv Regev,Steven A. McCarroll,Steven A. McCarroll +26 more
Massively parallel digital transcriptional profiling of single cells
Grace X.Y. Zheng,Jessica M. Terry,Phillip Belgrader,Paul Ryvkin,Zachary Bent,Ryan Wilson,Solongo B. Ziraldo,Tobias Daniel Wheeler,Geoffrey P. McDermott,Junjie Zhu,Mark T. Gregory,Joe Shuga,Luz Montesclaros,Jason G. Underwood,Donald A. Masquelier,Stefanie Y. Nishimura,Michael Schnall-Levin,Paul Wyatt,Christopher Hindson,Rajiv Bharadwaj,Alexander Wong,Kevin D. Ness,Lan Beppu,H. Joachim Deeg,Christopher McFarland,Keith R. Loeb,Keith R. Loeb,William J. Valente,William J. Valente,Nolan G. Ericson,Emily A. Stevens,Jerald P. Radich,Tarjei S. Mikkelsen,Benjamin J. Hindson,Jason H. Bielas +34 more