Potential for Pancreatic Maturation of Differentiating Human Embryonic Stem Cells Is Sensitive to the Specific Pathway of Definitive Endoderm Commitment

Details

• Alternative Title:
  PLoS One
• Personal Author:
  Jaramillo, Maria ; Mathew, Shibin ; Task, Keith ; Barner, Sierra ; Banerjee, Ipsita
• Description:
  This study provides a detailed experimental and mathematical analysis of the impact of the initial pathway of definitive endoderm (DE) induction on later stages of pancreatic maturation. Human embryonic stem cells (hESCs) were induced to insulin-producing cells following a directed-differentiation approach. DE was induced following four alternative pathway modulations. DE derivatives obtained from these alternate pathways were subjected to pancreatic progenitor (PP) induction and maturation and analyzed at each stage. Results indicate that late stage maturation is influenced by the initial pathway of DE commitment. Detailed quantitative analysis revealed WNT3A and FGF2 induced DE cells showed highest expression of insulin, are closely aligned in gene expression patterning and have a closer resemblance to pancreatic organogenesis. Conversely, BMP4 at DE induction gave most divergent differentiation dynamics with lowest insulin upregulation, but highest glucagon upregulation. Additionally, we have concluded that early analysis of PP markers is indicative of its potential for pancreatic maturation.
• Subjects:
  Biological Markers Cell Differentiation Cluster Analysis Embryonic Stem Cells Endoderm Humans Models, Biological Organogenesis Pancreas Principal Component Analysis Wnt3A Protein

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• Source:
  PLoS One. 2014; 9(4).
• Pubmed ID:
  24743345
• Pubmed Central ID:
  PMC3990550
• Document Type:
  Journal Article
• Funding:
  DP2 116520/DP/NCCDPHP CDC HHS/United States ; UL1 RR024153/RR/NCRR NIH HHS/United States ; UL1 TR000005/TR/NCATS NIH HHS/United States ; UL1TR000005/TR/NCATS NIH HHS/United States
• Volume:
  9
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:68f34e55bb3993a56f77a8064179ccce1e8dfad1c92d8d433c80b517fea44169
• Download URL:
  https://stacks.cdc.gov/view/cdc/32174/cdc_32174_DS1.pdf
• File Type:
  [PDF - 1.64 MB ]