Cargando…
Effect of Exogenous Transcription Factors Integration Sites on Safety and Pluripotency of Induced Pluripotent Stem Cells
Induced pluripotent stem cells (iPSCs), generated from somatic cells, not only possess similar characteristics with embryonic stem cells (ESCs), but also present more advantages than ESCs in medical applications. The classical induction method that utilizes the integration of exogenous genes into ch...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Sciendo
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474223/ https://www.ncbi.nlm.nih.gov/pubmed/32953404 http://dx.doi.org/10.2478/bjmg-2020-0003 |
_version_ | 1783579304301428736 |
---|---|
author | Yin, S Li, W Yang, G Cheng, Y Yi, Q Fan, S Ma, Q Zeng, F |
author_facet | Yin, S Li, W Yang, G Cheng, Y Yi, Q Fan, S Ma, Q Zeng, F |
author_sort | Yin, S |
collection | PubMed |
description | Induced pluripotent stem cells (iPSCs), generated from somatic cells, not only possess similar characteristics with embryonic stem cells (ESCs), but also present more advantages than ESCs in medical applications. The classical induction method that utilizes the integration of exogenous genes into chromosomes may raise the potential risk of the safety of iPSCs. To investigate the potential correlation between the integration sites of exogenous transcription factors (TFs) and iPSCs’ pluripotency and safety, the integration of exogenous genes in three iPSC lines, which met the golden standard of murine developmental assay (tetraploid complementation), were analyzed. Twenty-two integration sites of exogenous TFs were identified by nested inverse polymerase chain reaction (iPCR) and 39 flanking genes’ functions were analyzed by gene ontology (GO). In the 22 integrated sites, 17 (77.3%) were located in the intergenic regions and the remainder were located in introns far from the transcription start sites. Microarray analysis of the flanking genes in these cells showed that there was no distinct difference in expression levels between the iPSCs, ESCs and mouse embryonic fibroblast (MEF), suggesting that the integration of exogenous TFs has no significant influence on the expression of flanking genes. Gene ontology analysis showed that although most of the flanking genes were housekeeping genes, which were necessary for basic life activity, none of these 39 flanking genes have correlation with tumorigenesis or embryogenesis, suggesting that the integration sites hold low risk of tumorigenesis. |
format | Online Article Text |
id | pubmed-7474223 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Sciendo |
record_format | MEDLINE/PubMed |
spelling | pubmed-74742232020-09-17 Effect of Exogenous Transcription Factors Integration Sites on Safety and Pluripotency of Induced Pluripotent Stem Cells Yin, S Li, W Yang, G Cheng, Y Yi, Q Fan, S Ma, Q Zeng, F Balkan J Med Genet Original Article Induced pluripotent stem cells (iPSCs), generated from somatic cells, not only possess similar characteristics with embryonic stem cells (ESCs), but also present more advantages than ESCs in medical applications. The classical induction method that utilizes the integration of exogenous genes into chromosomes may raise the potential risk of the safety of iPSCs. To investigate the potential correlation between the integration sites of exogenous transcription factors (TFs) and iPSCs’ pluripotency and safety, the integration of exogenous genes in three iPSC lines, which met the golden standard of murine developmental assay (tetraploid complementation), were analyzed. Twenty-two integration sites of exogenous TFs were identified by nested inverse polymerase chain reaction (iPCR) and 39 flanking genes’ functions were analyzed by gene ontology (GO). In the 22 integrated sites, 17 (77.3%) were located in the intergenic regions and the remainder were located in introns far from the transcription start sites. Microarray analysis of the flanking genes in these cells showed that there was no distinct difference in expression levels between the iPSCs, ESCs and mouse embryonic fibroblast (MEF), suggesting that the integration of exogenous TFs has no significant influence on the expression of flanking genes. Gene ontology analysis showed that although most of the flanking genes were housekeeping genes, which were necessary for basic life activity, none of these 39 flanking genes have correlation with tumorigenesis or embryogenesis, suggesting that the integration sites hold low risk of tumorigenesis. Sciendo 2020-08-26 /pmc/articles/PMC7474223/ /pubmed/32953404 http://dx.doi.org/10.2478/bjmg-2020-0003 Text en © 2020 Yin S, Li W, Yang G, Cheng Y, Yi Q, Fan S, Ma Q, Zeng F, published by Sciendo http://creativecommons.org/licenses/by-nc-nd/3.0 This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. |
spellingShingle | Original Article Yin, S Li, W Yang, G Cheng, Y Yi, Q Fan, S Ma, Q Zeng, F Effect of Exogenous Transcription Factors Integration Sites on Safety and Pluripotency of Induced Pluripotent Stem Cells |
title | Effect of Exogenous Transcription Factors Integration Sites on Safety and Pluripotency of Induced Pluripotent Stem Cells |
title_full | Effect of Exogenous Transcription Factors Integration Sites on Safety and Pluripotency of Induced Pluripotent Stem Cells |
title_fullStr | Effect of Exogenous Transcription Factors Integration Sites on Safety and Pluripotency of Induced Pluripotent Stem Cells |
title_full_unstemmed | Effect of Exogenous Transcription Factors Integration Sites on Safety and Pluripotency of Induced Pluripotent Stem Cells |
title_short | Effect of Exogenous Transcription Factors Integration Sites on Safety and Pluripotency of Induced Pluripotent Stem Cells |
title_sort | effect of exogenous transcription factors integration sites on safety and pluripotency of induced pluripotent stem cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474223/ https://www.ncbi.nlm.nih.gov/pubmed/32953404 http://dx.doi.org/10.2478/bjmg-2020-0003 |
work_keys_str_mv | AT yins effectofexogenoustranscriptionfactorsintegrationsitesonsafetyandpluripotencyofinducedpluripotentstemcells AT liw effectofexogenoustranscriptionfactorsintegrationsitesonsafetyandpluripotencyofinducedpluripotentstemcells AT yangg effectofexogenoustranscriptionfactorsintegrationsitesonsafetyandpluripotencyofinducedpluripotentstemcells AT chengy effectofexogenoustranscriptionfactorsintegrationsitesonsafetyandpluripotencyofinducedpluripotentstemcells AT yiq effectofexogenoustranscriptionfactorsintegrationsitesonsafetyandpluripotencyofinducedpluripotentstemcells AT fans effectofexogenoustranscriptionfactorsintegrationsitesonsafetyandpluripotencyofinducedpluripotentstemcells AT maq effectofexogenoustranscriptionfactorsintegrationsitesonsafetyandpluripotencyofinducedpluripotentstemcells AT zengf effectofexogenoustranscriptionfactorsintegrationsitesonsafetyandpluripotencyofinducedpluripotentstemcells |