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Single-Cell Transcriptome Profiling Reveals ? Cell Maturation in Stem Cell-Derived Islets after Transplantation.

ABSTRACT: Human pluripotent stem cells differentiated to insulin-secreting ? cells (SC-? cells) in islet organoids could provide an unlimited cell source for diabetes cell replacement therapy. However, current SC-? cells generated in vitro are transcriptionally and functionally immature compared to native adult ? cells. Here, we use single-cell transcriptomic profiling to catalog changes that occur in transplanted SC-? cells. We find that transplanted SC-? cells exhibit drastic transcriptional changes and mature to more closely resemble adult ? cells. Insulin and IAPP protein secretions increase upon transplantation, along with expression of maturation genes lacking with differentiation in vitro, including INS, MAFA, CHGB, and G6PC2. Other differentiated cell types, such as SC-? and SC-enterochromaffin (SC-EC) cells, also exhibit large transcriptional changes. This study provides a comprehensive resource for understanding human islet cell maturation and provides important insights into maturation of SC-? cells and other SC-islet cell types to enable future differentiation strategy improvements.

SUBMITTER: Augsornworawat P

PROVIDER: S-EPMC7491368 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Single-Cell Transcriptome Profiling Reveals β Cell Maturation in Stem Cell-Derived Islets after Transplantation.

Augsornworawat Punn P Maxwell Kristina G KG Velazco-Cruz Leonardo L Millman Jeffrey R JR

Cell reports 20200801 8

Human pluripotent stem cells differentiated to insulin-secreting β cells (SC-β cells) in islet organoids could provide an unlimited cell source for diabetes cell replacement therapy. However, current SC-β cells generated in vitro are transcriptionally and functionally immature compared to native adult β cells. Here, we use single-cell transcriptomic profiling to catalog changes that occur in transplanted SC-β cells. We find that transplanted SC-β cells exhibit drastic transcriptional changes and ...[more]

PMID: 32846125

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Project description:BackgroundMammalian follicle development is characterized by extensive changes in morphology, endocrine responsiveness, and function, providing the optimum environment for oocyte growth, development, and resumption of meiosis. In cattle, the first signs of transcription activation in the oocyte are observed in the secondary follicle, later than during mouse and human oogenesis. While many studies have generated extensive datasets characterizing gene expression in bovine oocytes, they are mostly limited to the analysis of fully grown and matured oocytes. The aim of the present study was to apply single-cell RNA sequencing to interrogate the transcriptome of the growing bovine oocyte from the secondary follicle stage through to the mid-antral follicle stage.ResultsSingle-cell RNA-seq libraries were generated from oocytes of known diameters (< 60 to > 120 μm), and datasets were binned into non-overlapping size groups for downstream analysis. Combining the results of weighted gene co-expression network and Trendy analyses, and differently expressed genes (DEGs) between size groups, we identified a decrease in oxidative phosphorylation and an increase in maternal -genes and transcription regulators across the bovine oocyte growth phase. In addition, around 5,000 genes did not change in expression, revealing a cohort of stable genes. An interesting switch in gene expression profile was noted in oocytes greater than 100 μm in diameter, when the expression of genes related to cytoplasmic activities was replaced by genes related to nuclear activities (e.g., chromosome segregation). The highest number of DEGs were detected in the comparison of oocytes 100-109 versus 110-119 μm in diameter, revealing a profound change in the molecular profile of oocytes at the end of their growth phase.ConclusionsThe current study provides a unique dataset of the key genes and pathways characteristic of each stage of oocyte development, contributing an important resource for a greater understanding of bovine oogenesis.

Dataset Information

Single-Cell Transcriptome Profiling Reveals ? Cell Maturation in Stem Cell-Derived Islets after Transplantation.

Publications

Single-Cell Transcriptome Profiling Reveals β Cell Maturation in Stem Cell-Derived Islets after Transplantation.

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