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Potential for pancreatic maturation of differentiating human embryonic stem cells is sensitive to the specific pathway of definitive endoderm commitment

Jaramillo, M and Mathew, S and Task, K and Barner, S and Banerjee, I (2014) Potential for pancreatic maturation of differentiating human embryonic stem cells is sensitive to the specific pathway of definitive endoderm commitment. PLoS ONE, 9 (4).

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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. © 2014 Jaramillo et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Jaramillo, M
Mathew, Sshm82@pitt.eduSHM82
Task, K
Barner, Ssib16@pitt.eduSIB16
Banerjee, Iipb1@pitt.eduIPB1
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorLako, MajlindaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > McGowan Institute for Regenerative Medicine
Date: 17 April 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 4
DOI or Unique Handle: 10.1371/journal.pone.0094307
Schools and Programs: Swanson School of Engineering > Bioengineering
Swanson School of Engineering > Chemical and Petroleum Engineering
Refereed: Yes
Date Deposited: 23 Jun 2014 21:04
Last Modified: 04 Feb 2019 22:55
URI: http://d-scholarship.pitt.edu/id/eprint/21986

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