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

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  • Maria Jaramillo
  • Shibin Mathew
  • Keith Task
  • Sierra Barner
  • Ipsita Banerjee

Abstract

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.

Suggested Citation

  • Maria Jaramillo & Shibin Mathew & Keith Task & Sierra Barner & Ipsita Banerjee, 2014. "Potential for Pancreatic Maturation of Differentiating Human Embryonic Stem Cells Is Sensitive to the Specific Pathway of Definitive Endoderm Commitment," PLOS ONE, Public Library of Science, vol. 9(4), pages 1-14, April.
    • Handle: RePEc:plo:pone00:0094307
    DOI: 10.1371/journal.pone.0094307
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    1. Beatriz Sosa-Pineda & Kamal Chowdhury & Miguel Torres & Guillermo Oliver & Peter Gruss, 1997. "The Pax4 gene is essential for differentiation of insulin-producing β cells in the mammalian pancreas," Nature, Nature, vol. 386(6623), pages 399-402, March.
    2. Keith Task & Maria Jaramillo & Ipsita Banerjee, 2012. "Population Based Model of Human Embryonic Stem Cell (hESC) Differentiation during Endoderm Induction," PLOS ONE, Public Library of Science, vol. 7(3), pages 1-10, March.
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