Yang, Diane; Patel, Sanjeet; Szlachcic, Wojciech J.; Chmielowiec, Jolanta; Scaduto, Diane; Putluri, Nagireddy; Sreekumar, Arun; Suliburk, James; Metzker, Michael; Balasubramanyam, Ashok; Borowiak, Malgorzata published the artcile< Pancreatic differentiation of stem cells reveals pathogenesis of a syndrome of ketosis-prone diabetes>, Synthetic Route of 1223001-51-1, the main research area is human ketosis prone diabetes stem cell pancreatic differentiation PDX1.
Genetic anal. of an adult patient with an unusual course of ketosis-prone diabetes (KPD) and lacking islet autoantibodies demonstrated a nucleotide variant in the 5′-untranslated region (UTR) of PDX1, a β-cell development gene. When differentiated to the pancreatic lineage, his induced pluripotent stem cells stalled at the definitive endoderm (DE) stage. Metabolomics anal. of the cells revealed that this was associated with leucine hypersensitivity during transition fromthe DE to the pancreatic progenitor (PP) stage, and RNA sequencing showed that defects in leucine- sensitive mTOR pathways contribute to the differentiation deficiency. CRISPR/Cas9 manipulation of the PDX1 variant demonstrated that it is necessary and sufficient to confer leucine sensitivity and the differentiation block, likely due to disruption of binding of the transcriptional regulator NFY to the PDX1 5′-UTR, leading to decreased PDX1 expression at the early PP stage. Thus, the combination of an underlying defect in leucine catabolism characteristic of KPD with a functionally relevant heterozygous variant in a critical β-cell gene that confers increased leucine sensitivity and inhibits endocrine cell differentiation resulted in the phenotype of late-onset β-cell failure in this patient. We define themol. pathogenesis of a diabetes syndrome and demonstrate the power of multiomics anal. of patient-specific stemcells for clin. discovery.
Diabetespublished new progress about 5′-Untranslated region Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Synthetic Route of 1223001-51-1.
Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem