Generation of pancreatic progenitors from human pluripotent stem cells by small molecules. 2021

Yuqian Jiang, and Chuanxin Chen, and Lauren N Randolph, and Songtao Ye, and Xin Zhang, and Xiaoping Bao, and Xiaojun Lance Lian
Department of Biomedical Engineering, Pennsylvania State University, University Park, PA 16802, USA; Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.

Human pluripotent stem cell (hPSC)-derived pancreatic progenitors (PPs) provide promising cell therapies for type 1 diabetes. Current PP differentiation requires a high amount of Activin A during the definitive endoderm (DE) stage, making it economically difficult for commercial ventures. Here we identify a dose-dependent role for Wnt signaling in controlling DE differentiation without Activin A. While high-level Wnt activation induces mesodermal formation, low-level Wnt activation by a small-molecule inhibitor of glycogen synthase kinase 3 is sufficient for DE differentiation, yielding SOX17+FOXA2+ DE cells. BMP inhibition further enhances this DE differentiation, generating over 87% DE cells. These DE cells could be further differentiated into PPs and functional β cells. RNA-sequencing analysis of PP differentiation from hPSCs revealed expected transcriptome dynamics and new gene regulators during our small-molecule PP differentiation protocol. Overall, we established a robust growth-factor-free protocol for generating DE and PP cells, facilitating scalable production of pancreatic cells for regenerative applications.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D010179 Pancreas A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005455 Fluorescent Antibody Technique Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy. Antinuclear Antibody Test, Fluorescent,Coon's Technique,Fluorescent Antinuclear Antibody Test,Fluorescent Protein Tracing,Immunofluorescence Technique,Coon's Technic,Fluorescent Antibody Technic,Immunofluorescence,Immunofluorescence Technic,Antibody Technic, Fluorescent,Antibody Technics, Fluorescent,Antibody Technique, Fluorescent,Antibody Techniques, Fluorescent,Coon Technic,Coon Technique,Coons Technic,Coons Technique,Fluorescent Antibody Technics,Fluorescent Antibody Techniques,Fluorescent Protein Tracings,Immunofluorescence Technics,Immunofluorescence Techniques,Protein Tracing, Fluorescent,Protein Tracings, Fluorescent,Technic, Coon's,Technic, Fluorescent Antibody,Technic, Immunofluorescence,Technics, Fluorescent Antibody,Technics, Immunofluorescence,Technique, Coon's,Technique, Fluorescent Antibody,Technique, Immunofluorescence,Techniques, Fluorescent Antibody,Techniques, Immunofluorescence,Tracing, Fluorescent Protein,Tracings, Fluorescent Protein
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015415 Biomarkers Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc. Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune
D016130 Immunophenotyping Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry. Lymphocyte Immunophenotyping,Lymphocyte Subtyping,Immunologic Subtyping,Immunologic Subtypings,Lymphocyte Phenotyping,Subtyping, Immunologic,Subtypings, Immunologic,Immunophenotyping, Lymphocyte,Immunophenotypings,Immunophenotypings, Lymphocyte,Lymphocyte Immunophenotypings,Lymphocyte Phenotypings,Lymphocyte Subtypings,Phenotyping, Lymphocyte,Phenotypings, Lymphocyte,Subtyping, Lymphocyte,Subtypings, Lymphocyte
D050417 Insulin-Secreting Cells A type of pancreatic cell representing about 50-80% of the islet cells. Beta cells secrete INSULIN. Pancreatic beta Cells,beta Cells, Pancreatic,Pancreatic B Cells,B Cell, Pancreatic,B Cells, Pancreatic,Cell, Insulin-Secreting,Cells, Insulin-Secreting,Insulin Secreting Cells,Insulin-Secreting Cell,Pancreatic B Cell,Pancreatic beta Cell,beta Cell, Pancreatic
D059014 High-Throughput Nucleotide Sequencing Techniques of nucleotide sequence analysis that increase the range, complexity, sensitivity, and accuracy of results by greatly increasing the scale of operations and thus the number of nucleotides, and the number of copies of each nucleotide sequenced. The sequencing may be done by analysis of the synthesis or ligation products, hybridization to preexisting sequences, etc. High-Throughput Sequencing,Illumina Sequencing,Ion Proton Sequencing,Ion Torrent Sequencing,Next-Generation Sequencing,Deep Sequencing,High-Throughput DNA Sequencing,High-Throughput RNA Sequencing,Massively-Parallel Sequencing,Pyrosequencing,DNA Sequencing, High-Throughput,High Throughput DNA Sequencing,High Throughput Nucleotide Sequencing,High Throughput RNA Sequencing,High Throughput Sequencing,Massively Parallel Sequencing,Next Generation Sequencing,Nucleotide Sequencing, High-Throughput,RNA Sequencing, High-Throughput,Sequencing, Deep,Sequencing, High-Throughput,Sequencing, High-Throughput DNA,Sequencing, High-Throughput Nucleotide,Sequencing, High-Throughput RNA,Sequencing, Illumina,Sequencing, Ion Proton,Sequencing, Ion Torrent,Sequencing, Massively-Parallel,Sequencing, Next-Generation

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