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Series GSE240993 Query DataSets for GSE240993
Status Public on Aug 22, 2023
Title Dynamic regulation of pancreatic β cell function and gene expression by the SND1 coregulator in vitro
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The pancreatic β cell synthesizes, packages, and secretes insulin in response to glucose-stimulation to maintain blood glucose homeostasis. Under diabetic conditions, a subset of β cells fail and lose expression of key transcription factors (TFs) required for insulin secretion. Among these TFs is Pancreatic and duodenal homeobox 1 (Pdx1), which recruits a unique subset of transcriptional coregulators to modulate its activity. Here we describe a novel interacting partner of Pdx1, the Staphylococcal Nuclease and Tudor domain-containing protein (Snd1), which has been shown to facilitate protein-protein interactions and transcriptional control through diverse mechanisms in a variety of tissues. Pdx1:Snd1 interactions were confirmed in rodent β cell lines, mouse islets and human islets. Utilizing CRISPR-Cas9 gene editing technology, we deleted Snd1 from the mouse β cell lines, which revealed numerous differentially expressed genes linked to insulin secretion and cell proliferation, including limited expression of Glp1r. We observed Snd1 deficient β cell lines had reduced cell expansion rates, Glp1r protein levels and limited cAMP accumulation under stimulatory conditions, and further show that acute ablation of Snd1 impaired insulin secretion in rodent and human β cell lines. Lastly, we discovered that PDX1:SND1 interactions were profoundly reduced in human β cells from donors with type 2 diabetes (T2D). These observations suggest the Pdx1:Snd1 complex formation is critical for controlling a subset of genes important for β cell function and is targeted in diabetes pathogenesis
 
Overall design CRISPR/Cas9 was utilized to knockout Snd1 from mouse insulinoma MIN6 cell lines (Snd1 KO). RNA purified from 3 Control and 3 Snd1 KO cell lines was sequenced
 
Contributor(s) Spaeth J
Citation(s) 37838950
Submission date Aug 16, 2023
Last update date Oct 31, 2023
Contact name Jason Spaeth
E-mail(s) jspaeth@iu.edu
Phone 3172748986
Organization name Indiana University
Department Pediatrics
Lab MS2021
Street address 635 Barnhill Dr.
City Indianapolis
State/province IN
ZIP/Postal code 46202
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (6)
GSM7713454 Min6 cells, CN1
GSM7713455 Min6 cells, CN2
GSM7713456 Min6 cells, CN3
Relations
BioProject PRJNA1006013

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Supplementary file Size Download File type/resource
GSE240993_Processed_Snd1KO_DEG_and_GO.xlsx 27.5 Kb (ftp)(http) XLSX
GSE240993_RAW.tar 2.2 Mb (http)(custom) TAR (of TAB)
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Raw data are available in SRA

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