A human cell atlas of fetal gene expression

The gene expression program underlying the specification of human cell types is of fundamental interest. We generated human cell atlases of gene expression and chromatin accessibility in fetal tissues. For gene expression, we applied three-level combinatorial indexing to >110 samples representing...

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Bibliographic Details
Published in:	Science (American Association for the Advancement of Science) Vol. 370; no. 6518
Main Authors:	Cao, Junyue, O'Day, Diana R, Pliner, Hannah A, Kingsley, Paul D, Deng, Mei, Daza, Riza M, Zager, Michael A, Aldinger, Kimberly A, Blecher-Gonen, Ronnie, Zhang, Fan, Spielmann, Malte, Palis, James, Doherty, Dan, Steemers, Frank J, Glass, Ian A, Trapnell, Cole, Shendure, Jay
Format:	Journal Article
Language:	English
Published:	United States The American Association for the Advancement of Science 13-11-2020
Subjects:	Accessibility Adrenal glands Atlases as Topic Blood cells Cell differentiation Cell lines Chromatin Chromatin - metabolism Combinatorial analysis Data integration Developmental stages Embryogenesis Epigenetics Epithelial cells Erythropoiesis Fetus - cytology Fetus - metabolism Fetuses Gene expression Gene Expression Profiling Gene Expression Regulation, Developmental Genetics Hematopoietic stem cells Heterogeneity Human tissues Humans In vivo methods and tests Indexing Integration Neurons - metabolism Organs Proteomics Regulatory sequences Ribonucleic acid RNA Single-Cell Analysis Specifications Stem cell transplantation Stem cells Tissue analysis Tissues Transcription Factors - metabolism Websites
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Summary:	The gene expression program underlying the specification of human cell types is of fundamental interest. We generated human cell atlases of gene expression and chromatin accessibility in fetal tissues. For gene expression, we applied three-level combinatorial indexing to >110 samples representing 15 organs, ultimately profiling ~4 million single cells. We leveraged the literature and other atlases to identify and annotate hundreds of cell types and subtypes, both within and across tissues. Our analyses focused on organ-specific specializations of broadly distributed cell types (such as blood, endothelial, and epithelial), sites of fetal erythropoiesis (which notably included the adrenal gland), and integration with mouse developmental atlases (such as conserved specification of blood cells). These data represent a rich resource for the exploration of in vivo human gene expression in diverse tissues and cell types.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: J.C. developed techniques and performed sci-RNA-seq3 experiments with assistance from R.M.D., R.B., F.Z. and F.J.S.; D.R.O. and M.D. performed tissue collection, nuclei extraction and immunohistochemistry staining under supervision of D.D. and I.A.G.; K.A.A. performed genotyping; P.K. and J.P. performed erythropoiesis validation in mice; J.C. performed computational analyses with assistance from H.A.P. and M.S.; M.A.Z. developed website with assistance from J.C.; J.C. and J.S. wrote the manuscript with input from all co-authors; J.S. and C.T. supervised the project. Present address: Laboratory of Single-Cell Genomics and Population Dynamics, The Rockefeller University, New York, NY, USA.
ISSN:	0036-8075 1095-9203
DOI:	10.1126/science.aba7721