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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MDPI AG
2022-11-01
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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. |
first_indexed | 2024-03-09T17:51:12Z |
format | Article |
id | doaj.art-39c4c427f4f94eb58e7f671008663588 |
institution | Directory Open Access Journal |
issn | 2073-4409 |
language | English |
last_indexed | 2024-03-09T17:51:12Z |
publishDate | 2022-11-01 |
publisher | MDPI AG |
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series | Cells |
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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