The role of FOSL1 in stem-like cell reprogramming processes
Abstract Cancer stem-like cells (CSCs) have self-renewal abilities responsible for cancer progression, therapy resistance, and metastatic growth. The glioblastoma stem-like cells are the most studied among CSC populations. A recent study identified four transcription factors (SOX2, SALL2, OLIG2, and...
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Nature Portfolio
2021-07-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-021-94072-0 |
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author | Valeria Pecce Antonella Verrienti Giulia Fiscon Marialuisa Sponziello Federica Conte Luana Abballe Cosimo Durante Lorenzo Farina Sebastiano Filetti Paola Paci |
author_facet | Valeria Pecce Antonella Verrienti Giulia Fiscon Marialuisa Sponziello Federica Conte Luana Abballe Cosimo Durante Lorenzo Farina Sebastiano Filetti Paola Paci |
author_sort | Valeria Pecce |
collection | DOAJ |
description | Abstract Cancer stem-like cells (CSCs) have self-renewal abilities responsible for cancer progression, therapy resistance, and metastatic growth. The glioblastoma stem-like cells are the most studied among CSC populations. A recent study identified four transcription factors (SOX2, SALL2, OLIG2, and POU3F2) as the minimal core sufficient to reprogram differentiated glioblastoma (GBM) cells into stem-like cells. Transcriptomic data of GBM tissues and cell lines from two different datasets were then analyzed by the SWItch Miner (SWIM), a network-based software, and FOSL1 was identified as a putative regulator of the previously identified minimal core. Herein, we selected NTERA-2 and HEK293T cells to perform an in vitro study to investigate the role of FOSL1 in the reprogramming mechanisms. We transfected the two cell lines with a constitutive FOSL1 cDNA plasmid. We demonstrated that FOSL1 directly regulates the four transcription factors binding their promoter regions, is involved in the deregulation of several stemness markers, and reduces the cells’ ability to generate aggregates increasing the extracellular matrix component FN1. Although further experiments are necessary, our data suggest that FOSL1 reprograms the stemness by regulating the core of the four transcription factors. |
first_indexed | 2024-12-20T21:41:46Z |
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id | doaj.art-cd1c4f27242a4ec8a9ec2d8affe631c5 |
institution | Directory Open Access Journal |
issn | 2045-2322 |
language | English |
last_indexed | 2024-12-20T21:41:46Z |
publishDate | 2021-07-01 |
publisher | Nature Portfolio |
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series | Scientific Reports |
spelling | doaj.art-cd1c4f27242a4ec8a9ec2d8affe631c52022-12-21T19:25:48ZengNature PortfolioScientific Reports2045-23222021-07-0111111110.1038/s41598-021-94072-0The role of FOSL1 in stem-like cell reprogramming processesValeria Pecce0Antonella Verrienti1Giulia Fiscon2Marialuisa Sponziello3Federica Conte4Luana Abballe5Cosimo Durante6Lorenzo Farina7Sebastiano Filetti8Paola Paci9Department of Translational and Precision Medicine, Sapienza University of RomeDepartment of Translational and Precision Medicine, Sapienza University of RomeFondazione Per La Medicina PersonalizzataDepartment of Translational and Precision Medicine, Sapienza University of RomeInstitute for Systems Analysis and Computer Science “Antonio Ruberti”, National Research CouncilDepartment of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS, Ospedale Pediatrico Bambino GesùDepartment of Translational and Precision Medicine, Sapienza University of RomeDepartment of Computer, Control, and Management Engineering, Sapienza University of RomeSchool of Health, Unitelma Sapienza University of RomeInstitute for Systems Analysis and Computer Science “Antonio Ruberti”, National Research CouncilAbstract Cancer stem-like cells (CSCs) have self-renewal abilities responsible for cancer progression, therapy resistance, and metastatic growth. The glioblastoma stem-like cells are the most studied among CSC populations. A recent study identified four transcription factors (SOX2, SALL2, OLIG2, and POU3F2) as the minimal core sufficient to reprogram differentiated glioblastoma (GBM) cells into stem-like cells. Transcriptomic data of GBM tissues and cell lines from two different datasets were then analyzed by the SWItch Miner (SWIM), a network-based software, and FOSL1 was identified as a putative regulator of the previously identified minimal core. Herein, we selected NTERA-2 and HEK293T cells to perform an in vitro study to investigate the role of FOSL1 in the reprogramming mechanisms. We transfected the two cell lines with a constitutive FOSL1 cDNA plasmid. We demonstrated that FOSL1 directly regulates the four transcription factors binding their promoter regions, is involved in the deregulation of several stemness markers, and reduces the cells’ ability to generate aggregates increasing the extracellular matrix component FN1. Although further experiments are necessary, our data suggest that FOSL1 reprograms the stemness by regulating the core of the four transcription factors.https://doi.org/10.1038/s41598-021-94072-0 |
spellingShingle | Valeria Pecce Antonella Verrienti Giulia Fiscon Marialuisa Sponziello Federica Conte Luana Abballe Cosimo Durante Lorenzo Farina Sebastiano Filetti Paola Paci The role of FOSL1 in stem-like cell reprogramming processes Scientific Reports |
title | The role of FOSL1 in stem-like cell reprogramming processes |
title_full | The role of FOSL1 in stem-like cell reprogramming processes |
title_fullStr | The role of FOSL1 in stem-like cell reprogramming processes |
title_full_unstemmed | The role of FOSL1 in stem-like cell reprogramming processes |
title_short | The role of FOSL1 in stem-like cell reprogramming processes |
title_sort | role of fosl1 in stem like cell reprogramming processes |
url | https://doi.org/10.1038/s41598-021-94072-0 |
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