Inhibition of JAK-STAT ERK/MAPK and Glycogen Synthase Kinase-3 Induces a Change in Gene Expression Profile of Bovine Induced Pluripotent Stem Cells

Pluripotent stem cells (PSCs) fall in two states, one highly undifferentiated, the naïve state, and the primed state, characterized by the inability to contribute to germinal lineage. Several reports have demonstrated that these states can be modified by changes to the cell culture conditions. With...

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Main Authors: Luis F. Malaver-Ortega, Huseyin Sumer, Jun Liu, Paul J. Verma
Format: Article
Language:English
Published: Hindawi Limited 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/5127984
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spelling doaj-f602ee5ad523433083789c77b765f99a2020-11-24T21:17:52ZengHindawi LimitedStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/51279845127984Inhibition of JAK-STAT ERK/MAPK and Glycogen Synthase Kinase-3 Induces a Change in Gene Expression Profile of Bovine Induced Pluripotent Stem CellsLuis F. Malaver-Ortega0Huseyin Sumer1Jun Liu2Paul J. Verma3CSIRO Health & Biosecurity, East Geelong, VIC 3219, AustraliaFaculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, VIC 3122, AustraliaDepartment of Materials Engineering, Monash Institute of Medical Engineering, Faculty of Engineering, Monash University, Clayton, VIC 3168, AustraliaDepartment of Materials Engineering, Monash Institute of Medical Engineering, Faculty of Engineering, Monash University, Clayton, VIC 3168, AustraliaPluripotent stem cells (PSCs) fall in two states, one highly undifferentiated, the naïve state, and the primed state, characterized by the inability to contribute to germinal lineage. Several reports have demonstrated that these states can be modified by changes to the cell culture conditions. With the advent of nuclear reprogramming, bovine induced pluripotent stem cells (biPSCs) have been generated. These cells represent examples of a transient-intermediate state of pluripotency with remarkable characteristics and biotechnological potential. Herein, we generated and characterized biPSC. Next, we evaluated different culture conditions for the ability to affect the expression of the set of core pluripotent transcription factors in biPSC. It was found that the use of 6-bromoindirubin-3-oxime and Sc1 inhibitors alone or in combination with 5-AzaC induced significantly higher levels of expression of endogenous REX1, OCT4, NANOG, and SOX2. Furthermore, LIF increased the levels of expression of OCT4 and REX1, compared with those cultured with LIF + bFGF. By contrast, bFGF decreased the levels of expression for both REX1 and OCT4. These results demonstrate that the biPSC gene expression profile is malleable by modification of the cell culture conditions well after nuclear reprogramming, and the culture conditions may determine their differentiation potential.http://dx.doi.org/10.1155/2016/5127984
collection DOAJ
language English
format Article
sources DOAJ
author Luis F. Malaver-Ortega
Huseyin Sumer
Jun Liu
Paul J. Verma
spellingShingle Luis F. Malaver-Ortega
Huseyin Sumer
Jun Liu
Paul J. Verma
Inhibition of JAK-STAT ERK/MAPK and Glycogen Synthase Kinase-3 Induces a Change in Gene Expression Profile of Bovine Induced Pluripotent Stem Cells
Stem Cells International
author_facet Luis F. Malaver-Ortega
Huseyin Sumer
Jun Liu
Paul J. Verma
author_sort Luis F. Malaver-Ortega
title Inhibition of JAK-STAT ERK/MAPK and Glycogen Synthase Kinase-3 Induces a Change in Gene Expression Profile of Bovine Induced Pluripotent Stem Cells
title_short Inhibition of JAK-STAT ERK/MAPK and Glycogen Synthase Kinase-3 Induces a Change in Gene Expression Profile of Bovine Induced Pluripotent Stem Cells
title_full Inhibition of JAK-STAT ERK/MAPK and Glycogen Synthase Kinase-3 Induces a Change in Gene Expression Profile of Bovine Induced Pluripotent Stem Cells
title_fullStr Inhibition of JAK-STAT ERK/MAPK and Glycogen Synthase Kinase-3 Induces a Change in Gene Expression Profile of Bovine Induced Pluripotent Stem Cells
title_full_unstemmed Inhibition of JAK-STAT ERK/MAPK and Glycogen Synthase Kinase-3 Induces a Change in Gene Expression Profile of Bovine Induced Pluripotent Stem Cells
title_sort inhibition of jak-stat erk/mapk and glycogen synthase kinase-3 induces a change in gene expression profile of bovine induced pluripotent stem cells
publisher Hindawi Limited
series Stem Cells International
issn 1687-966X
1687-9678
publishDate 2016-01-01
description Pluripotent stem cells (PSCs) fall in two states, one highly undifferentiated, the naïve state, and the primed state, characterized by the inability to contribute to germinal lineage. Several reports have demonstrated that these states can be modified by changes to the cell culture conditions. With the advent of nuclear reprogramming, bovine induced pluripotent stem cells (biPSCs) have been generated. These cells represent examples of a transient-intermediate state of pluripotency with remarkable characteristics and biotechnological potential. Herein, we generated and characterized biPSC. Next, we evaluated different culture conditions for the ability to affect the expression of the set of core pluripotent transcription factors in biPSC. It was found that the use of 6-bromoindirubin-3-oxime and Sc1 inhibitors alone or in combination with 5-AzaC induced significantly higher levels of expression of endogenous REX1, OCT4, NANOG, and SOX2. Furthermore, LIF increased the levels of expression of OCT4 and REX1, compared with those cultured with LIF + bFGF. By contrast, bFGF decreased the levels of expression for both REX1 and OCT4. These results demonstrate that the biPSC gene expression profile is malleable by modification of the cell culture conditions well after nuclear reprogramming, and the culture conditions may determine their differentiation potential.
url http://dx.doi.org/10.1155/2016/5127984
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