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Series GSE79457 Query DataSets for GSE79457
Status Public on Feb 16, 2017
Title Converting adult pancreatic α-cells into β-cells by targeting Dnmt1 and Arx
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary After their destruction in adult mice, insulin-producing pancreatic beta-cells slowly regenerate from other islet cells, like glucagon-producing alpha-cells. However the molecular basis of this conversion is unknown. Moreover it remains unclear if this intra-islet cell conversion is relevant to human diseases with extensive beta-cell loss, like in type 1 diabetes (T1D). Here, we show that subsets of glucagon-expressing cells in subjects with T1D produce Insulin and other molecular features of beta-cells, accompanied by loss of the alpha-cell regulators DNA methyltransferase 1 (Dnmt1) and Aristaless-related homeobox (Arx). We generated mice permitting lineage tracing and inactivation of Dnmt1 and Arx in adult alpha-cells. Within 3 months of Dnmt1 and Arx loss, 50% of alpha-cells converted into cells producing insulin protein but not glucagon, changes not observed in alpha-cells after only Arx or Dnmt1 loss. Single cell isolation and high-throughput RNA sequencing revealed efficient and extensive alpha-cell conversion into progeny indistinguishable by global gene expression from native beta-cells. Our work reveals pathways regulated by Arx and Dnmt1 sufficient for achieving targeted generation of beta-cells from adult pancreatic alpha-cells.
Overall design Single-cell RNA-seq of in-vivo conversion of pancreatic α-cells into β-cells
Contributor(s) Enge M, Chakravarthy H
Citation(s) 28215845
Submission date Mar 21, 2016
Last update date Sep 05, 2019
Contact name Martin Enge
Organization name Stanford University
Department Bioengineering
Lab Stephen Quake
Street address James H. Clark Center, 318 Campus Drive,
City Stanford
State/province CA
ZIP/Postal code 94305
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (182)
GSM2096686 mouse_YFPpos_8w_cell1
GSM2096687 mouse_YFPpos_8w_cell2
GSM2096688 mouse_YFPpos_8w_cell3
BioProject PRJNA316075
SRA SRP072214

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Supplementary file Size Download File type/resource
GSE79457_RAW.tar 12.7 Mb (http)(custom) TAR (of CSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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