Combined Noncoding RNA-mRNA Regulomics Signature in Reprogramming and Pluripotency in iPSCs

Somatic cells are reprogrammed with reprogramming factors to generate induced pluripotent stem cells (iPSCs), offering a promising future for disease modeling and treatment by overcoming the limitations of embryonic stem cells. However, this process remains inefficient since only a small percentage...

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Main Authors: Salam Salloum-Asfar, Sara A. Abdulla, Rowaida Z. Taha, I. Richard Thompson, Mohamed M. Emara
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/11/23/3833
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author Salam Salloum-Asfar
Sara A. Abdulla
Rowaida Z. Taha
I. Richard Thompson
Mohamed M. Emara
author_facet Salam Salloum-Asfar
Sara A. Abdulla
Rowaida Z. Taha
I. Richard Thompson
Mohamed M. Emara
author_sort Salam Salloum-Asfar
collection DOAJ
description Somatic cells are reprogrammed with reprogramming factors to generate induced pluripotent stem cells (iPSCs), offering a promising future for disease modeling and treatment by overcoming the limitations of embryonic stem cells. However, this process remains inefficient since only a small percentage of transfected cells can undergo full reprogramming. Introducing miRNAs, such as miR-294 and miR302/3667, with reprogramming factors, has shown to increase iPSC colony formation. Previously, we identified five transcription factors, GBX2, NANOGP8, SP8, PEG3, and ZIC1, which may boost iPSC generation. In this study, we performed quantitative miRNAome and small RNA-seq sequencing and applied our previously identified transcriptome to identify the potential miRNA–mRNA regulomics and regulatory network of other ncRNAs. From each fibroblast (N = 4), three iPSC clones were examined (N = 12). iPSCs and original fibroblasts expressed miRNA clusters differently and miRNA clusters were compared to mRNA hits. Moreover, miRNA, piRNA, and snoRNAs expression profiles in iPSCs and original fibroblasts were assessed to identify the potential role of ncRNAs in enhancing iPSC generation, pluripotency, and differentiation. Decreased levels of let-7a-5p showed an increase of SP8 as described previously. Remarkably, the targets of identifier miRNAs were grouped into pluripotency canonical pathways, on stemness, cellular development, growth and proliferation, cellular assembly, and organization of iPSCs.
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spelling doaj.art-39c4c427f4f94eb58e7f6710086635882023-11-24T10:44:32ZengMDPI AGCells2073-44092022-11-011123383310.3390/cells11233833Combined Noncoding RNA-mRNA Regulomics Signature in Reprogramming and Pluripotency in iPSCsSalam Salloum-Asfar0Sara A. Abdulla1Rowaida Z. Taha2I. Richard Thompson3Mohamed M. Emara4Neurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, QatarNeurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, QatarNeurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, QatarQatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, QatarBasic Medical Sciences Department, College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, QatarSomatic cells are reprogrammed with reprogramming factors to generate induced pluripotent stem cells (iPSCs), offering a promising future for disease modeling and treatment by overcoming the limitations of embryonic stem cells. However, this process remains inefficient since only a small percentage of transfected cells can undergo full reprogramming. Introducing miRNAs, such as miR-294 and miR302/3667, with reprogramming factors, has shown to increase iPSC colony formation. Previously, we identified five transcription factors, GBX2, NANOGP8, SP8, PEG3, and ZIC1, which may boost iPSC generation. In this study, we performed quantitative miRNAome and small RNA-seq sequencing and applied our previously identified transcriptome to identify the potential miRNA–mRNA regulomics and regulatory network of other ncRNAs. From each fibroblast (N = 4), three iPSC clones were examined (N = 12). iPSCs and original fibroblasts expressed miRNA clusters differently and miRNA clusters were compared to mRNA hits. Moreover, miRNA, piRNA, and snoRNAs expression profiles in iPSCs and original fibroblasts were assessed to identify the potential role of ncRNAs in enhancing iPSC generation, pluripotency, and differentiation. Decreased levels of let-7a-5p showed an increase of SP8 as described previously. Remarkably, the targets of identifier miRNAs were grouped into pluripotency canonical pathways, on stemness, cellular development, growth and proliferation, cellular assembly, and organization of iPSCs.https://www.mdpi.com/2073-4409/11/23/3833noncoding RNAsmiRNAspiRNAssnoRNAsiPSCsreprogramming
spellingShingle Salam Salloum-Asfar
Sara A. Abdulla
Rowaida Z. Taha
I. Richard Thompson
Mohamed M. Emara
Combined Noncoding RNA-mRNA Regulomics Signature in Reprogramming and Pluripotency in iPSCs
Cells
noncoding RNAs
miRNAs
piRNAs
snoRNAs
iPSCs
reprogramming
title Combined Noncoding RNA-mRNA Regulomics Signature in Reprogramming and Pluripotency in iPSCs
title_full Combined Noncoding RNA-mRNA Regulomics Signature in Reprogramming and Pluripotency in iPSCs
title_fullStr Combined Noncoding RNA-mRNA Regulomics Signature in Reprogramming and Pluripotency in iPSCs
title_full_unstemmed Combined Noncoding RNA-mRNA Regulomics Signature in Reprogramming and Pluripotency in iPSCs
title_short Combined Noncoding RNA-mRNA Regulomics Signature in Reprogramming and Pluripotency in iPSCs
title_sort combined noncoding rna mrna regulomics signature in reprogramming and pluripotency in ipscs
topic noncoding RNAs
miRNAs
piRNAs
snoRNAs
iPSCs
reprogramming
url https://www.mdpi.com/2073-4409/11/23/3833
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