Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA89803 | ENA |
REPOSITORIES: ENA
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Project description:The generation of pancreatic organoids from human pluripotent stem cells represents a major breakthrough for regenerative medicine and the modeling of diseases such as diabetes. However, current approaches remain inefficient due to lengthy multi-step differentiation protocols and limited functional maturity in the organoids. In this study, we overcome these challenges using multi-phase optimization screens to achieve rapid generation of functionally mature pancreatic organoids from a stable endocrine progenitor culture. We conducted stepwise culture condition screens that enabled the stable culture of multiple pancreatic progenitor cell states, including the unprecedented stable propagation of NEUROD1-expressing endocrine progenitor-like cells (EpSCs). Further transcriptomic profiling of EpSC confirmed similarity of that to previously reported endocrine progenitor populations. Using EpSCs, we significantly reduced the number of steps and timing required to generate pancreatic organoids, enabling rapid testing of conditions for organoid maturation. Utilizing this optimized protocol, we further tested conditions to promote pancreatic organoid maturation. We identified that exosome-delivered WNT5B, in combination with RSPO1 (exoW/R), could strongly induce non-canonical WNT/JNK signaling, promoting pancreatic organoid maturation. This combinatorial exosome treatment enhances epithelial organization, reduces immature cell states, and significantly improves glucose responsiveness and insulin secretion. Collectively, our work establishes a robust pancreatic differentiation platform that integrates long-term progenitor expansion with optimized organoid maturation. This system provides a reproducible experimental framework for studying pancreatic development, investigating disease mechanisms, and facilitating future translational applications involving pancreatic organoids.
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Project description:Both in situ synthesized long oligo arrays from Agilent Technologies and short oligo arrays from Affymetrix were used to meausre differential gene expression in RNA samples generated from (1) human neural stem cells treated with vehicle (EtOH, 0.01%) and tert-butylhydroquinone (tBHQ, 20µM) for 24h, and (2) neuroblastoma cells treated with vehicle (EtOH, 0.01%) and tert-butylhydroquinone (tBHQ, 10µM) for 24h. This SuperSeries is composed of the following subset Series:; GSE759: Long oligonucleotide arrays verse short oligonucleotide arrays-CTX066; GSE761: Long oligonucleotide arrays verse short oligonucleotide arrays -IMR32 cells Experiment Overall Design: Refer to individual Series
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Project description:Single-nucleus RNA sequencing (snRNA-seq) was used to profile the transcriptome of 16,015 nuclei in human adult testis. This dataset includes five samples from two different individuals. This dataset is part of a larger evolutionary study of adult testis at the single-nucleus level (97,521 single-nuclei in total) across mammals including 10 representatives of the three main mammalian lineages: human, chimpanzee, bonobo, gorilla, gibbon, rhesus macaque, marmoset, mouse (placental mammals); grey short-tailed opossum (marsupials); and platypus (egg-laying monotremes). Corresponding data were generated for a bird (red junglefowl, the progenitor of domestic chicken), to be used as an evolutionary outgroup.
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