{"database":"ENA","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Fastqsanger.gz":["ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR223/079/SRR22302379/SRR22302379_2.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR223/081/SRR22302381/SRR22302381_2.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR223/080/SRR22302380/SRR22302380_1.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR223/083/SRR22302383/SRR22302383_2.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR223/082/SRR22302382/SRR22302382_1.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR223/085/SRR22302385/SRR22302385_1.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR223/079/SRR22302379/SRR22302379_1.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR223/080/SRR22302380/SRR22302380_2.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR223/082/SRR22302382/SRR22302382_2.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR223/084/SRR22302384/SRR22302384_2.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR223/083/SRR22302383/SRR22302383_1.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR223/081/SRR22302381/SRR22302381_1.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR223/085/SRR22302385/SRR22302385_2.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR223/084/SRR22302384/SRR22302384_1.fastq.gz"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Genomics"],"center_name":["Columbia University"],"full_dataset_link":["https://www.ebi.ac.uk/ena/browser/view/PRJNA901979"],"scientific_name":["Mus musculus"],"tag":["xref:PubMed:36732513"],"long_description":["Type 2 diabetes (T2D) is associated with defective insulin secretion, reduced β-cell mass, and β-cell dedifferentiation. Aldehyde dehydrogenase 1 isoform A3 (ALHD1A3) serves as a marker of β-cell dedifferentiation and correlates with T2D progression. ALDH1A3-positive β-cells (A+) demonstrate impaired insulin secretion, and their numbers decrease when diabetic mice are rendered euglycemic by pair-feeding. It is unknown whether ALDH1A3 activity contributes to β-cell failure, and whether the decrease of A+ cells under pair-feeding is due to β-cell restoration. To tackle these questions, we (i) investigated the fate of A+ cells during pair-feeding by lineage-tracing, (ii) somatically ablated ALDH1A3 in diabetic β-cells, and (iii) used a novel selective ALDH1A3 inhibitor to treat diabetes. Lineage tracing and functional characterization show that A+ cells can be reconverted to functional, mature β-cells. Genetic or pharmacological inhibition of ALDH1A3 in diabetic mice lowers glycemia and increases insulin secretion. Molecular interrogation of β-cells following ALDH1A3 inhibition show a reactivation of differentiation as well as regeneration pathways through the REG gene family. We conclude that ALDH1A3 inhibition offers a therapeutic strategy for β-cell dysfunction in diabetes. Overall design: Sorted beta cells from db/db, db/+ or Aldh1a3 KO_db/db mice"],"repository":["ENA"],"additional_accession":[]},"is_claimable":false,"name":"Genetic and pharmacologic inhibition of ALDH1A3 as a treatment of β-cell failure","description":"Genetic and pharmacologic inhibition of ALDH1A3 as a treatment of β-cell failure","dates":{"last_updated":"2025-09-24","first_public":"2023-01-20"},"accession":"PRJNA901979","cross_references":{"GEO":["GSE218047"],"taxon":["10090"],"PubMed":["36732513"]}}