Insertion/deletion and microsatellite alteration profiles in induced pluripotent stem cells
| Autor: | Kaori Imadome, Yuko Hoki, Satoshi Kamimura, Mayumi Fujita, Ryoko Araki, Misato Sunayama, Miki Nakamura, Masumi Abe, Tomo Suga |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
genome reprogramming
Somatic cell Cell Induced Pluripotent Stem Cells cord blood erythroblasts Biology Biochemistry Genome Article Mice microsatellite alterations sister clones set INDEL Mutation Genetics medicine Insertion deletion Animals Humans Cellular Reprogramming Techniques Indel Induced pluripotent stem cell Cells Cultured Whole genome sequencing InDels mouse iPSCs Whole Genome Sequencing Cell Biology Genetic Profile mouse ntESCs Cellular Reprogramming Cell biology Mice Inbred C57BL hotspots of microsatellite alteration medicine.anatomical_structure whole-genome sequencing Microsatellite human iPSCs Developmental Biology Microsatellite Repeats |
| Zdroj: | Stem Cell Reports |
| ISSN: | 2213-6711 |
| Popis: | Summary We here demonstrate that microsatellite (MS) alterations are elevated in both mouse and human induced pluripotent stem cells (iPSCs), but importantly we have now identified a type of human iPSC in which these alterations are considerably reduced. We aimed in our present analyses to profile the InDels in iPSC/ntESC genomes, especially in MS regions. To detect somatic de novo mutations in particular, we generated 13 independent reprogramed stem cell lines (11 iPSC and 2 ntESC lines) from an identical parent somatic cell fraction of a C57BL/6 mouse. By using this cell set with an identical genetic background, we could comprehensively detect clone-specific alterations and, importantly, experimentally validate them. The effectiveness of employing sister clones for detecting somatic de novo mutations was thereby demonstrated. We then successfully applied this approach to human iPSCs. Our results require further careful genomic analysis but make an important inroad into solving the issue of genome abnormalities in iPSCs. Graphical abstract Highlights • InDels and microsatellite alterations are elevated in iPSCs • These alterations are reduced in human iPSCs derived from cord blood erythroblasts • Employing sister clones is an effective way to detect somatic de novo mutations In this article, Abe and colleagues conclusively demonstrate that InDels and microsatellite alterations are elevated in reprogrammed pluripotent stem cells, both mouse and human, by employing sister clones and conducting large-scale validation experiments. Furthermore, they show that these alterations are considerably reduced in human iPSCs derived from cord blood erythroblasts. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|