title: Potential for pancreatic maturation of differentiating human embryonic stem cells is sensitive to the specific pathway of definitive endoderm commitment.
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.
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Maria
authors.initials: M
authors.lastname: Jaramillo
authors.affiliation: Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Shibin
authors.initials: S
authors.lastname: Mathew
authors.affiliation: Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Keith
authors.initials: K
authors.lastname: Task
authors.affiliation: Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Sierra
authors.initials: S
authors.lastname: Barner
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Ipsita
authors.initials: I
authors.lastname: Banerjee
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D016000:Cluster Analysis; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D004707:Endoderm / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D038081:Organogenesis; D010179:Pancreas / Q000196:embryology*; D025341:Principal Component Analysis; D060509:Wnt3A Protein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D060509:Wnt3A Protein
references.citation: Nat Biotechnol. 2006 Nov;24(11):1392-401
references.pmid: 17053790
references.citation: Genes Dev. 2008 Aug 1;22(15):1998-2021
references.pmid: 18676806
references.citation: Development. 2004 Jul;131(13):3069-80
references.pmid: 15163629
references.citation: J Biol Chem. 2007 Oct 26;282(43):31703-12
references.pmid: 17711862
references.citation: Cell Stem Cell. 2009 Apr 3;4(4):348-58
references.pmid: 19341624
references.citation: Diabetes Obes Metab. 2011 Oct;13 Suppl 1:13-20
references.pmid: 21824252
references.citation: Development. 2004 Apr;131(7):1651-62
references.pmid: 14998924
references.citation: Integr Biol (Camb). 2009 Sep;1(8-9):540-51
references.pmid: 20023769
references.citation: Nat Biotechnol. 2008 Apr;26(4):443-52
references.pmid: 18288110
references.citation: Development. 2000 Dec;127(24):5533-40
references.pmid: 11076772
references.citation: Stem Cell Res. 2012 Mar;8(2):274-84
references.pmid: 22056147
references.citation: Curr Opin Genet Dev. 2002 Oct;12(5):540-7
references.pmid: 12200159
references.citation: Expert Opin Biol Ther. 2011 Jan;11(1):41-53
references.pmid: 21110785
references.citation: Endocrinology. 2012 Sep;153(9):4204-15
references.pmid: 22778220
references.citation: J Tissue Eng Regen Med. 2015 Jan;9(1):1-12
references.pmid: 23008262
references.citation: Nature. 1997 Mar 27;386(6623):399-402
references.pmid: 9121556
references.citation: Genes Dev. 2001 Feb 1;15(3):304-15
references.pmid: 11159911
references.citation: Mol Cells. 2004 Dec 31;18(3):289-94
references.pmid: 15650323
references.citation: Dev Cell. 2007 Mar;12(3):457-65
references.pmid: 17336910
references.citation: Sci China C Life Sci. 2009 Jul;52(7):615-21
references.pmid: 19641866
references.citation: BMC Syst Biol. 2012 Dec 15;6:154
references.pmid: 23241383
references.citation: Stem Cells Dev. 2007 Aug;16(4):561-78
references.pmid: 17784830
references.citation: J Endocrinol. 2010 Jul;206(1):13-26
references.pmid: 20385725
references.citation: Diabetes Care. 2010 Mar;33(3):562-8
references.pmid: 20067953
references.citation: J Cell Physiol. 2010 Jan;222(1):103-10
references.pmid: 19774559
references.citation: Pancreas. 2012 Jan;41(1):65-73
references.pmid: 21792086
references.citation: Stem Cells. 2012 Apr;30(4):631-42
references.pmid: 22893457
references.citation: Development. 2011 Mar;138(5):861-71
references.pmid: 21270052
references.citation: Stem Cells. 2010 Jan;28(1):45-56
references.pmid: 19890880
references.citation: Mech Dev. 2011 Sep-Dec;128(7-10):412-27
references.pmid: 21855631
references.citation: PLoS One. 2009 Jun 30;4(6):e6082
references.pmid: 19564924
references.citation: Stem Cell Rev. 2005;1(2):131-8
references.pmid: 17142847
references.citation: Stem Cells. 2007 Jan;25(1):29-38
references.pmid: 17204604
references.citation: J Biol Eng. 2013 Apr 09;7(1):9
references.pmid: 23570553
references.citation: J Cell Sci. 2011 Jun 15;124(Pt 12):1992-2000
references.pmid: 21610099
references.citation: Nat Genet. 1999 Aug;22(4):361-5
references.pmid: 10431240
references.citation: PLoS One. 2012;7(3):e32975
references.pmid: 22427920
references.citation: J Cell Biol. 1997 Jun 2;137(5):1127-36
references.pmid: 9166412
references.citation: Cell Stem Cell. 2012 Mar 2;10(3):312-26
references.pmid: 22385658
references.citation: Gastroenterology. 2010 Jun;138(7):2233-45, 2245.e1-14
references.pmid: 20206178
references.citation: Stem Cell Res. 2009 Sep-Nov;3(2-3):73-87
references.pmid: 19766074
references.citation: Cell Stem Cell. 2011 Mar 4;8(3):326-34
references.pmid: 21362572
references.citation: Diabetologia. 2004 Apr;47(4):597-613
references.pmid: 15298336
references.citation: Diabetes Technol Ther. 2011 Mar;13(3):395-418
references.pmid: 21299398
references.citation: PLoS Biol. 2010 May 25;8(5):e1000379
references.pmid: 20520791
references.citation: Annu Rev Cell Dev Biol. 2009;25:221-51
references.pmid: 19575677
references.citation: Science. 2008 Dec 5;322(5907):1490-4
references.pmid: 19056973