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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
E-mail(s) martin.enge@gmail.com
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
Relations
BioProject PRJNA316075
SRA SRP072214

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

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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