Chromosomal aberration arises during somatic reprogramming to pluripotent stem cells
Abstract Background Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) has opened new therapeutic possibilities. However, karyotypic abnormalities detected in iPSCs compromised their utility, especially chromosomal aberrations found at early passages raised serious safety concerns...
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BMC
2020-11-01
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| Series: | Cell Division |
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| Online Access: | http://link.springer.com/article/10.1186/s13008-020-00068-z |
| _version_ | 1811295691772788736 |
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| author | Xinyu Liu Conghui Li Kang Zheng Xiaofeng Zhao Xiaofeng Xu Aifen Yang Min Yi Huaping Tao Binghua Xie Mengsheng Qiu Junlin Yang |
| author_facet | Xinyu Liu Conghui Li Kang Zheng Xiaofeng Zhao Xiaofeng Xu Aifen Yang Min Yi Huaping Tao Binghua Xie Mengsheng Qiu Junlin Yang |
| author_sort | Xinyu Liu |
| collection | DOAJ |
| description | Abstract Background Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) has opened new therapeutic possibilities. However, karyotypic abnormalities detected in iPSCs compromised their utility, especially chromosomal aberrations found at early passages raised serious safety concerns. The mechanism underlying the chromosomal abnormality in early-passage iPSCs is not known. Methods Human dermal fibroblasts (HDFs) were stimulated with KMOS (KLF4, cMYC, OCT4 and SOX2) proteins to enhance their proliferative capacity and many vigorous clones were obtained. Clonal reprogramming was carried out by KMOS mRNAs transfection to confirm the ‘chromosomal mutagenicity’ of reprogramming process. Subculturing was performed to examine karyotypic stability of iPSCs after the re-establishment of stemness. And antioxidant N-acetyl-cysteine (NAC) was added to the culture medium for further confirmming the mutagenicity in the first few days of reprogramming. Results Chromosomal aberrations were found in a small percentage of newly induced iPS clones by reprogramming transcription factors. Clonal reprogramming ruled out the aberrant chromosomes inherited from rare karyotypically abnormal parental cell subpopulation. More importantly, the antioxidant NAC effectively reduced the occurrence of chromosomal aberrations at the early stage of reprogramming. Once iPS cell lines were established, they restored karyotypic stability in subsequent subculturing. Conclusions Our results provided the first line of evidence for the ‘chromosomal mutagenicity’ of reprogramming process. |
| first_indexed | 2024-04-13T05:36:22Z |
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| institution | Directory Open Access Journal |
| issn | 1747-1028 |
| language | English |
| last_indexed | 2024-04-13T05:36:22Z |
| publishDate | 2020-11-01 |
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| series | Cell Division |
| spelling | doaj.art-12188d0d7acd4bc98e0437d92ff512b22022-12-22T03:00:15ZengBMCCell Division1747-10282020-11-0115111310.1186/s13008-020-00068-zChromosomal aberration arises during somatic reprogramming to pluripotent stem cellsXinyu Liu0Conghui Li1Kang Zheng2Xiaofeng Zhao3Xiaofeng Xu4Aifen Yang5Min Yi6Huaping Tao7Binghua Xie8Mengsheng Qiu9Junlin Yang10Key Laboratory of Organ Development and Regeneration of Zhejiang Province, College of Life and Environmental Sciences, Hangzhou Normal UniversityKey Laboratory of Organ Development and Regeneration of Zhejiang Province, College of Life and Environmental Sciences, Hangzhou Normal UniversityKey Laboratory of Organ Development and Regeneration of Zhejiang Province, College of Life and Environmental Sciences, Hangzhou Normal UniversityKey Laboratory of Organ Development and Regeneration of Zhejiang Province, College of Life and Environmental Sciences, Hangzhou Normal UniversityKey Laboratory of Organ Development and Regeneration of Zhejiang Province, College of Life and Environmental Sciences, Hangzhou Normal UniversityKey Laboratory of Organ Development and Regeneration of Zhejiang Province, College of Life and Environmental Sciences, Hangzhou Normal UniversityKey Laboratory of Organ Development and Regeneration of Zhejiang Province, College of Life and Environmental Sciences, Hangzhou Normal UniversityKey Laboratory of Organ Development and Regeneration of Zhejiang Province, College of Life and Environmental Sciences, Hangzhou Normal UniversityKey Laboratory of Organ Development and Regeneration of Zhejiang Province, College of Life and Environmental Sciences, Hangzhou Normal UniversityKey Laboratory of Organ Development and Regeneration of Zhejiang Province, College of Life and Environmental Sciences, Hangzhou Normal UniversityKey Laboratory of Organ Development and Regeneration of Zhejiang Province, College of Life and Environmental Sciences, Hangzhou Normal UniversityAbstract Background Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) has opened new therapeutic possibilities. However, karyotypic abnormalities detected in iPSCs compromised their utility, especially chromosomal aberrations found at early passages raised serious safety concerns. The mechanism underlying the chromosomal abnormality in early-passage iPSCs is not known. Methods Human dermal fibroblasts (HDFs) were stimulated with KMOS (KLF4, cMYC, OCT4 and SOX2) proteins to enhance their proliferative capacity and many vigorous clones were obtained. Clonal reprogramming was carried out by KMOS mRNAs transfection to confirm the ‘chromosomal mutagenicity’ of reprogramming process. Subculturing was performed to examine karyotypic stability of iPSCs after the re-establishment of stemness. And antioxidant N-acetyl-cysteine (NAC) was added to the culture medium for further confirmming the mutagenicity in the first few days of reprogramming. Results Chromosomal aberrations were found in a small percentage of newly induced iPS clones by reprogramming transcription factors. Clonal reprogramming ruled out the aberrant chromosomes inherited from rare karyotypically abnormal parental cell subpopulation. More importantly, the antioxidant NAC effectively reduced the occurrence of chromosomal aberrations at the early stage of reprogramming. Once iPS cell lines were established, they restored karyotypic stability in subsequent subculturing. Conclusions Our results provided the first line of evidence for the ‘chromosomal mutagenicity’ of reprogramming process.http://link.springer.com/article/10.1186/s13008-020-00068-zInduced pluripotent stem cellReprogrammeKaryotypeChromosomal aberrationGenetic stability |
| spellingShingle | Xinyu Liu Conghui Li Kang Zheng Xiaofeng Zhao Xiaofeng Xu Aifen Yang Min Yi Huaping Tao Binghua Xie Mengsheng Qiu Junlin Yang Chromosomal aberration arises during somatic reprogramming to pluripotent stem cells Cell Division Induced pluripotent stem cell Reprogramme Karyotype Chromosomal aberration Genetic stability |
| title | Chromosomal aberration arises during somatic reprogramming to pluripotent stem cells |
| title_full | Chromosomal aberration arises during somatic reprogramming to pluripotent stem cells |
| title_fullStr | Chromosomal aberration arises during somatic reprogramming to pluripotent stem cells |
| title_full_unstemmed | Chromosomal aberration arises during somatic reprogramming to pluripotent stem cells |
| title_short | Chromosomal aberration arises during somatic reprogramming to pluripotent stem cells |
| title_sort | chromosomal aberration arises during somatic reprogramming to pluripotent stem cells |
| topic | Induced pluripotent stem cell Reprogramme Karyotype Chromosomal aberration Genetic stability |
| url | http://link.springer.com/article/10.1186/s13008-020-00068-z |
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