TY - JOUR
T1 - iPSC-Derived Glioblastoma Cells Have Enhanced Stemness Wnt/β-Catenin Activity Which Is Negatively Regulated by Wnt Antagonist sFRP4
AU - Yasmin, Ishmat Ara
AU - Dharmarajan, Arun
AU - Warrier, Sudha
N1 - Funding Information:
This work was supported partly by funding from the Department of Biotechnology, Ministry of Science and Technology, India [BT/PR41903/MED/97/527/2021] and Department of Health Research, Ministry of Health and Family Welfare, India [R.11013/27/2021-GIA/HR].
Funding Information:
I.A.Y. is thankful for fellowship from Council of Scientific and Industrial Research (CSIR), Government of India.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/7
Y1 - 2023/7
N2 - Growing evidence indicates that cancer stem cells (CSCs) endow the tumor with stem-like properties. Recently, induced pluripotent stem cells (iPSCs) have gained increased attention because of their easy derivation and availability and their potential to differentiate into any cell type. A CSC model derived from iPSCs of human origin would help understand the driving force of tumor initiation and early progression. We report the efficient generation of feeder-free SSEA4, TRA-1-60 and TRA-1-81 positive iPSCs from amniotic membrane-derived mesenchymal stem cells (AMMSCs), which successfully differentiated into three germ layers. We then developed human iPSC-derived glioblastoma multiforme (GBM) model using conditioned media (CM) from U87MG cell line and CSCs derived from U87MG, which confer iPSCs with GBM and GSC-like phenotypes within five days. Both cell types overexpress MGMT and GLI2, but only GSCs overexpress CD133, CD44, ABCG2 and ABCC2. We also observed overexpression of LEF1 and β-catenin in both cell types. Down-regulation of Wnt antagonist secreted frizzled-related protein 4 (sFRP4) in GBM and GSCs, indicating activation of the Wnt/β-catenin pathway, which could be involved in the conversion of iPSCs to CSCs. From future perspectives, our study will help in the creation of a rapid cell-based platform for understanding the complexity of GBM.
AB - Growing evidence indicates that cancer stem cells (CSCs) endow the tumor with stem-like properties. Recently, induced pluripotent stem cells (iPSCs) have gained increased attention because of their easy derivation and availability and their potential to differentiate into any cell type. A CSC model derived from iPSCs of human origin would help understand the driving force of tumor initiation and early progression. We report the efficient generation of feeder-free SSEA4, TRA-1-60 and TRA-1-81 positive iPSCs from amniotic membrane-derived mesenchymal stem cells (AMMSCs), which successfully differentiated into three germ layers. We then developed human iPSC-derived glioblastoma multiforme (GBM) model using conditioned media (CM) from U87MG cell line and CSCs derived from U87MG, which confer iPSCs with GBM and GSC-like phenotypes within five days. Both cell types overexpress MGMT and GLI2, but only GSCs overexpress CD133, CD44, ABCG2 and ABCC2. We also observed overexpression of LEF1 and β-catenin in both cell types. Down-regulation of Wnt antagonist secreted frizzled-related protein 4 (sFRP4) in GBM and GSCs, indicating activation of the Wnt/β-catenin pathway, which could be involved in the conversion of iPSCs to CSCs. From future perspectives, our study will help in the creation of a rapid cell-based platform for understanding the complexity of GBM.
UR - https://www.scopus.com/pages/publications/85167481100
UR - https://www.scopus.com/inward/citedby.url?scp=85167481100&partnerID=8YFLogxK
U2 - 10.3390/cancers15143622
DO - 10.3390/cancers15143622
M3 - Article
AN - SCOPUS:85167481100
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 14
M1 - 3622
ER -
