A Single-Cell Transcriptomic Map of the Human and Mouse Pancreas Reveals Inter- and Intra-cell Population Structure
Although the function of the mammalian pancreas hinges on complex interactions of distinct cell types, gene expression profiles have primarily been described with bulk mixtures. Here we implemented a droplet-based, single-cell RNA-seq method to determine the transcriptomes of over 12,000 individual...
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| Published in | Cell systems Vol. 3; no. 4; pp. 346 - 360.e4 |
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| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
26.10.2016
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Although the function of the mammalian pancreas hinges on complex interactions of distinct cell types, gene expression profiles have primarily been described with bulk mixtures. Here we implemented a droplet-based, single-cell RNA-seq method to determine the transcriptomes of over 12,000 individual pancreatic cells from four human donors and two mouse strains. Cells could be divided into 15 clusters that matched previously characterized cell types: all endocrine cell types, including rare epsilon-cells; exocrine cell types; vascular cells; Schwann cells; quiescent and activated stellate cells; and four types of immune cells. We detected subpopulations of ductal cells with distinct expression profiles and validated their existence with immuno-histochemistry stains. Moreover, among human beta- cells, we detected heterogeneity in the regulation of genes relating to functional maturation and levels of ER stress. Finally, we deconvolved bulk gene expression samples using the single-cell data to detect disease-associated differential expression. Our dataset provides a resource for the discovery of novel cell type-specific transcription factors, signaling receptors, and medically relevant genes.
[Display omitted]
•We report over 12,000 individual pancreatic cell transcriptomes in human and mouse•We detect novel expression of TFs, signaling receptors, and medically relevant genes•We identify subpopulations and heterogeneity within pancreatic cell types•We deconvolve bulk gene expression samples using the single-cell data
Single-cell transcriptomics of over 12,000 cells from four human donors and two mouse strains was determined using inDrop. Cells were divided into 15 clusters that matched previously characterized cell types. Detailed analysis of each population separately revealed subpopulations within the ductal population, modes of activation of stellate cells, and heterogeneity in the stress among beta cells. |
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| AbstractList | Although the function of the mammalian pancreas hinges on complex interactions of distinct cell types, gene expression profiles have primarily been described with bulk mixtures. Here we implemented a droplet-based, single-cell RNA-seq method to determine the transcriptomes of over 12,000 individual pancreatic cells from four human donors and two mouse strains. Cells could be divided into 15 clusters that matched previously characterized cell types: all endocrine cell types, including rare epsilon-cells; exocrine cell types; vascular cells; Schwann cells; quiescent and activated stellate cells; and four types of immune cells. We detected subpopulations of ductal cells with distinct expression profiles and validated their existence with immuno-histochemistry stains. Moreover, among human beta- cells, we detected heterogeneity in the regulation of genes relating to functional maturation and levels of ER stress. Finally, we deconvolved bulk gene expression samples using the single-cell data to detect disease-associated differential expression. Our dataset provides a resource for the discovery of novel cell type-specific transcription factors, signaling receptors, and medically relevant genes.
Single-cell transcriptomics of over 12,000 cells from four human donors and two mouse strains was determined using inDrop. Cells were divided into 15 clusters that matched previously characterized cell types. Detailed analysis of each population separately revealed subpopulations within the ductal population, modes of activation of stellate cells, and heterogeneity in the stress among beta cells. Although the function of the mammalian pancreas hinges on complex interactions of distinct cell types, gene expression profiles have primarily been described with bulk mixtures. Here we implemented a droplet-based, single-cell RNA-seq method to determine the transcriptomes of over 12,000 individual pancreatic cells from four human donors and two mouse strains. Cells could be divided into 15 clusters that matched previously characterized cell types: all endocrine cell types, including rare epsilon-cells; exocrine cell types; vascular cells; Schwann cells; quiescent and activated stellate cells; and four types of immune cells. We detected subpopulations of ductal cells with distinct expression profiles and validated their existence with immuno-histochemistry stains. Moreover, among human beta- cells, we detected heterogeneity in the regulation of genes relating to functional maturation and levels of ER stress. Finally, we deconvolved bulk gene expression samples using the single-cell data to detect disease-associated differential expression. Our dataset provides a resource for the discovery of novel cell type-specific transcription factors, signaling receptors, and medically relevant genes. Although the function of the mammalian pancreas hinges on complex interactions of distinct cell types, gene expression profiles have primarily been described with bulk mixtures. Here we implemented a droplet-based, single-cell RNA-seq method to determine the transcriptomes of over 12,000 individual pancreatic cells from four human donors and two mouse strains. Cells could be divided into 15 clusters that matched previously characterized cell types: all endocrine cell types, including rare epsilon-cells; exocrine cell types; vascular cells; Schwann cells; quiescent and activated stellate cells; and four types of immune cells. We detected subpopulations of ductal cells with distinct expression profiles and validated their existence with immuno-histochemistry stains. Moreover, among human beta- cells, we detected heterogeneity in the regulation of genes relating to functional maturation and levels of ER stress. Finally, we deconvolved bulk gene expression samples using the single-cell data to detect disease-associated differential expression. Our dataset provides a resource for the discovery of novel cell type-specific transcription factors, signaling receptors, and medically relevant genes. Although the function of the mammalian pancreas hinges on complex interactions of distinct cell types, gene expression profiles have primarily been described with bulk mixtures. Here we implemented a droplet-based, single-cell RNA-seq method to determine the transcriptomes of over 12,000 individual pancreatic cells from four human donors and two mouse strains. Cells could be divided into 15 clusters that matched previously characterized cell types: all endocrine cell types, including rare epsilon-cells; exocrine cell types; vascular cells; Schwann cells; quiescent and activated stellate cells; and four types of immune cells. We detected subpopulations of ductal cells with distinct expression profiles and validated their existence with immuno-histochemistry stains. Moreover, among human beta- cells, we detected heterogeneity in the regulation of genes relating to functional maturation and levels of ER stress. Finally, we deconvolved bulk gene expression samples using the single-cell data to detect disease-associated differential expression. Our dataset provides a resource for the discovery of novel cell type-specific transcription factors, signaling receptors, and medically relevant genes. [Display omitted] •We report over 12,000 individual pancreatic cell transcriptomes in human and mouse•We detect novel expression of TFs, signaling receptors, and medically relevant genes•We identify subpopulations and heterogeneity within pancreatic cell types•We deconvolve bulk gene expression samples using the single-cell data Single-cell transcriptomics of over 12,000 cells from four human donors and two mouse strains was determined using inDrop. Cells were divided into 15 clusters that matched previously characterized cell types. Detailed analysis of each population separately revealed subpopulations within the ductal population, modes of activation of stellate cells, and heterogeneity in the stress among beta cells. |
| Author | Gaujoux, Renaud Faust, Aubrey L. Wagner, Bridget K. Ryu, Jennifer Hyoje Veres, Adrian Vetere, Amedeo Baron, Maayan Melton, Douglas A. Yanai, Itai Shen-Orr, Shai S. Klein, Allon M. Wolock, Samuel L. |
| AuthorAffiliation | 3 Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA 1 Faculty of Biology, Technion – Israel Institute of Technology, Haifa 3200003, Israel 2 Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA 5 Center for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142, USA 4 Department of Immunology, Faculty of Medicine, Technion – Israel Institute of Technology, Haifa 3200003, Israel |
| AuthorAffiliation_xml | – name: 1 Faculty of Biology, Technion – Israel Institute of Technology, Haifa 3200003, Israel – name: 2 Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA – name: 4 Department of Immunology, Faculty of Medicine, Technion – Israel Institute of Technology, Haifa 3200003, Israel – name: 5 Center for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142, USA – name: 3 Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA |
| Author_xml | – sequence: 1 givenname: Maayan surname: Baron fullname: Baron, Maayan organization: Faculty of Biology, Technion – Israel Institute of Technology, Haifa 3200003, Israel – sequence: 2 givenname: Adrian surname: Veres fullname: Veres, Adrian organization: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA – sequence: 3 givenname: Samuel L. surname: Wolock fullname: Wolock, Samuel L. organization: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA – sequence: 4 givenname: Aubrey L. surname: Faust fullname: Faust, Aubrey L. organization: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA – sequence: 5 givenname: Renaud surname: Gaujoux fullname: Gaujoux, Renaud organization: Department of Immunology, Faculty of Medicine, Technion – Israel Institute of Technology, Haifa 3200003, Israel – sequence: 6 givenname: Amedeo surname: Vetere fullname: Vetere, Amedeo organization: Center for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142, USA – sequence: 7 givenname: Jennifer Hyoje surname: Ryu fullname: Ryu, Jennifer Hyoje organization: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA – sequence: 8 givenname: Bridget K. surname: Wagner fullname: Wagner, Bridget K. organization: Center for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142, USA – sequence: 9 givenname: Shai S. surname: Shen-Orr fullname: Shen-Orr, Shai S. organization: Department of Immunology, Faculty of Medicine, Technion – Israel Institute of Technology, Haifa 3200003, Israel – sequence: 10 givenname: Allon M. surname: Klein fullname: Klein, Allon M. email: allon_klein@hms.harvard.edu organization: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA – sequence: 11 givenname: Douglas A. surname: Melton fullname: Melton, Douglas A. email: dmelton@harvard.edu organization: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA – sequence: 12 givenname: Itai surname: Yanai fullname: Yanai, Itai email: itai.yanai@nyumc.org organization: Faculty of Biology, Technion – Israel Institute of Technology, Haifa 3200003, Israel |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27667365$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | Animals Cell Differentiation Gene Expression Profiling Gene Expression Regulation, Developmental Humans Islets of Langerhans Mice Pancreas Pancreas, Exocrine Single-Cell Analysis Transcription Factors Transcriptome |
| Title | A Single-Cell Transcriptomic Map of the Human and Mouse Pancreas Reveals Inter- and Intra-cell Population Structure |
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