Abstract
This study provides an assessment of the Fluidigm C1 platform for RNA sequencing of single mouse pancreatic islet cells. The system combines microfluidic technology and nanoliter-scale reactions. We sequenced 622 cells, allowing identification of 341 islet cells with high-quality gene expression profiles. The cells clustered into populations of α-cells (5%), β-cells (92%), δ-cells (1%), and pancreatic polypeptide cells (2%). We identified cell-type-specific transcription factors and pathways primarily involved in nutrient sensing and oxidation and cell signaling. Unexpectedly, 281 cells had to be removed from the analysis due to low viability, low sequencing quality, or contamination resulting in the detection of more than one islet hormone. Collectively, we provide a resource for identification of high-quality gene expression datasets to help expand insights into genes and pathways characterizing islet cell types. We reveal limitations in the C1 Fluidigm cell capture process resulting in contaminated cells with altered gene expression patterns. This calls for caution when interpreting single-cell transcriptomics data using the C1 Fluidigm system.
Keywords
Fluidigm C1
glucagon
insulin
pancreatic islet cells
single-cell RNA sequencing
MeSH Terms
Animals
Islets of Langerhans/cytology,metabolism
Mice
Mice, Inbred C57BL
Sequence Analysis, RNA/methods
Transcription Factors/metabolism
Chemicals
Transcription Factors
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Xin Yurong
Regeneron Pharmaceuticals, Tarrytown, NY 10591.
Kim Jinrang
Regeneron Pharmaceuticals, Tarrytown, NY 10591.
Ni Min
Regeneron Pharmaceuticals, Tarrytown, NY 10591.
Wei Yi
Regeneron Pharmaceuticals, Tarrytown, NY 10591.
Okamoto Haruka
Regeneron Pharmaceuticals, Tarrytown, NY 10591.
Lee Joseph
Regeneron Pharmaceuticals, Tarrytown, NY 10591.
Adler Christina
Regeneron Pharmaceuticals, Tarrytown, NY 10591.
Cavino Katie
Regeneron Pharmaceuticals, Tarrytown, NY 10591.
Murphy Andrew J
Regeneron Pharmaceuticals, Tarrytown, NY 10591.
Yancopoulos George D
Regeneron Pharmaceuticals, Tarrytown, NY 10591 george@regeneron.com Jesper.Gromada@regeneron.com.
Lin Hsin Chieh
Regeneron Pharmaceuticals, Tarrytown, NY 10591.
Gromada Jesper
Regeneron Pharmaceuticals, Tarrytown, NY 10591 george@regeneron.com Jesper.Gromada@regeneron.com.
References (22)
22 references, click to expand
-
Single-cell transcript analysis of pancreas development.
Dev Cell. 2003 Mar;4(3):383-93
PMID: 12636919
-
Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing.
Nature. 2013 Aug 29;500(7464):593-7
PMID: 23892778
-
A census of human transcription factors: function, expression and evolution.
Nat Rev Genet. 2009 Apr;10(4):252-63
PMID: 19274049
-
Cell-type, allelic, and genetic signatures in the human pancreatic beta cell transcriptome.
Genome Res. 2013 Sep;23(9):1554-62
PMID: 23716500
-
Quantitative assessment of single-cell RNA-sequencing methods.
Nat Methods. 2014 Jan;11(1):41-6
PMID: 24141493
-
In vivo reprogramming of pancreatic acinar cells to three islet endocrine subtypes.
Elife. 2014;3:e01846
PMID: 24714494
-
Single-cell RNA-seq reveals dynamic paracrine control of cellular variation.
Nature. 2014 Jun 19;510(7505):363-9
PMID: 24919153
-
Low-coverage single-cell mRNA sequencing reveals cellular heterogeneity and activated signaling pathways in developing cerebral cortex.
Nat Biotechnol. 2014 Oct;32(10):1053-8
PMID: 25086649
-
Diabetes recovery by age-dependent conversion of pancreatic δ-cells into insulin producers.
Nature. 2014 Oct 23;514(7523):503-7
PMID: 25141178
-
Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq.
Science. 2015 Mar 6;347(6226):1138-42
PMID: 25700174
-
Single-cell messenger RNA sequencing reveals rare intestinal cell types.
Nature. 2015 Sep 10;525(7568):251-5
PMID: 26287467
-
Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss.
Elife. 2015;4. doi: 10.7554/eLife.09800
PMID: 26329458
-
In vivo reprogramming of adult pancreatic exocrine cells to beta-cells.
Nature. 2008 Oct 2;455(7213):627-32
PMID: 18754011
-
Single pancreatic beta cells co-express multiple islet hormone genes in mice.
Diabetologia. 2010 Jan;53(1):128-38
PMID: 19851748
-
Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss.
Nature. 2010 Apr 22;464(7292):1149-54
PMID: 20364121
-
Transcriptomes of the major human pancreatic cell types.
Diabetologia. 2011 Nov;54(11):2832-44
PMID: 21882062
-
RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues.
J Mol Diagn. 2012 Jan;14(1):22-9
PMID: 22166544
-
Pancreatic organogenesis--developmental mechanisms and implications for therapy.
Nat Rev Genet. 2002 Jul;3(7):524-32
PMID: 12094230
-
Diabetes mellitus and the β cell: the last ten years.
Cell. 2012 Mar 16;148(6):1160-71
PMID: 22424227
-
Epigenomic plasticity enables human pancreatic α to β cell reprogramming.
J Clin Invest. 2013 Mar;123(3):1275-84
PMID: 23434589
-
Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells.
Nature. 2013 Jun 13;498(7453):236-40
PMID: 23685454
-
Single-cell transcriptomes reveal characteristic features of human pancreatic islet cell types.
EMBO Rep. 2016 Feb;17(2):178-87
PMID: 26691212