CRISPR/Cas9-mediated editing of ACTB in induced pluripotent stem cells: A model for investigating human ACTB loss-of-function and genetic adaptive responses
Heterozygous beta-actin (ACTB) indel and nonsense mutations are linked to developmental disorders. We generated two CRISPR/Cas9 human induced pluripotent stem cell (iPSC) lines, WTSIi018-B-19 and WTSIi018-B-20, carrying heterozygous and homozygous indel mutations in ACTB exon 4. Both iPSCs exhibited...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-06-01
|
| Series: | Stem Cell Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S187350612400093X |
| _version_ | 1797248345309184000 |
|---|---|
| author | Stephanie Binder Haribaskar Ramachandran Denise Haslinger Barbara Hildebrandt Jochen Dobner Thomas Haarmann-Stemmann Andreas Chiocchetti Andrea Rossi |
| author_facet | Stephanie Binder Haribaskar Ramachandran Denise Haslinger Barbara Hildebrandt Jochen Dobner Thomas Haarmann-Stemmann Andreas Chiocchetti Andrea Rossi |
| author_sort | Stephanie Binder |
| collection | DOAJ |
| description | Heterozygous beta-actin (ACTB) indel and nonsense mutations are linked to developmental disorders. We generated two CRISPR/Cas9 human induced pluripotent stem cell (iPSC) lines, WTSIi018-B-19 and WTSIi018-B-20, carrying heterozygous and homozygous indel mutations in ACTB exon 4. Both iPSCs exhibited normal cell morphology, expression of pluripotency markers, and the ability to differentiate into the three primary germ layers. While iPSCs with a heterozygous ACTB mutation maintain genome integrity, homozygous mutants showed a loss of heterozygosity in chromosome three. These mutants provide a powerful model to study the onset, progression, and complex interplay of genetic compensation and phenotypic variation of ACTB-related diseases. |
| first_indexed | 2024-04-24T20:13:07Z |
| format | Article |
| id | doaj.art-641301e5755e44058761de3d25563abf |
| institution | Directory Open Access Journal |
| issn | 1873-5061 |
| language | English |
| last_indexed | 2024-04-24T20:13:07Z |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj.art-641301e5755e44058761de3d25563abf2024-03-23T06:23:32ZengElsevierStem Cell Research1873-50612024-06-0177103395CRISPR/Cas9-mediated editing of ACTB in induced pluripotent stem cells: A model for investigating human ACTB loss-of-function and genetic adaptive responsesStephanie Binder0Haribaskar Ramachandran1Denise Haslinger2Barbara Hildebrandt3Jochen Dobner4Thomas Haarmann-Stemmann5Andreas Chiocchetti6Andrea Rossi7IUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, GermanyIUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, GermanyDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Molecular Genetics Laboratory, Goethe University Frankfurt, GermanyInstitute of Human Genetics, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, GermanyIUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, GermanyIUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, GermanyDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Molecular Genetics Laboratory, Goethe University Frankfurt, GermanyIUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany; Corresponding author.Heterozygous beta-actin (ACTB) indel and nonsense mutations are linked to developmental disorders. We generated two CRISPR/Cas9 human induced pluripotent stem cell (iPSC) lines, WTSIi018-B-19 and WTSIi018-B-20, carrying heterozygous and homozygous indel mutations in ACTB exon 4. Both iPSCs exhibited normal cell morphology, expression of pluripotency markers, and the ability to differentiate into the three primary germ layers. While iPSCs with a heterozygous ACTB mutation maintain genome integrity, homozygous mutants showed a loss of heterozygosity in chromosome three. These mutants provide a powerful model to study the onset, progression, and complex interplay of genetic compensation and phenotypic variation of ACTB-related diseases.http://www.sciencedirect.com/science/article/pii/S187350612400093X |
| spellingShingle | Stephanie Binder Haribaskar Ramachandran Denise Haslinger Barbara Hildebrandt Jochen Dobner Thomas Haarmann-Stemmann Andreas Chiocchetti Andrea Rossi CRISPR/Cas9-mediated editing of ACTB in induced pluripotent stem cells: A model for investigating human ACTB loss-of-function and genetic adaptive responses Stem Cell Research |
| title | CRISPR/Cas9-mediated editing of ACTB in induced pluripotent stem cells: A model for investigating human ACTB loss-of-function and genetic adaptive responses |
| title_full | CRISPR/Cas9-mediated editing of ACTB in induced pluripotent stem cells: A model for investigating human ACTB loss-of-function and genetic adaptive responses |
| title_fullStr | CRISPR/Cas9-mediated editing of ACTB in induced pluripotent stem cells: A model for investigating human ACTB loss-of-function and genetic adaptive responses |
| title_full_unstemmed | CRISPR/Cas9-mediated editing of ACTB in induced pluripotent stem cells: A model for investigating human ACTB loss-of-function and genetic adaptive responses |
| title_short | CRISPR/Cas9-mediated editing of ACTB in induced pluripotent stem cells: A model for investigating human ACTB loss-of-function and genetic adaptive responses |
| title_sort | crispr cas9 mediated editing of actb in induced pluripotent stem cells a model for investigating human actb loss of function and genetic adaptive responses |
| url | http://www.sciencedirect.com/science/article/pii/S187350612400093X |
| work_keys_str_mv | AT stephaniebinder crisprcas9mediatededitingofactbininducedpluripotentstemcellsamodelforinvestigatinghumanactblossoffunctionandgeneticadaptiveresponses AT haribaskarramachandran crisprcas9mediatededitingofactbininducedpluripotentstemcellsamodelforinvestigatinghumanactblossoffunctionandgeneticadaptiveresponses AT denisehaslinger crisprcas9mediatededitingofactbininducedpluripotentstemcellsamodelforinvestigatinghumanactblossoffunctionandgeneticadaptiveresponses AT barbarahildebrandt crisprcas9mediatededitingofactbininducedpluripotentstemcellsamodelforinvestigatinghumanactblossoffunctionandgeneticadaptiveresponses AT jochendobner crisprcas9mediatededitingofactbininducedpluripotentstemcellsamodelforinvestigatinghumanactblossoffunctionandgeneticadaptiveresponses AT thomashaarmannstemmann crisprcas9mediatededitingofactbininducedpluripotentstemcellsamodelforinvestigatinghumanactblossoffunctionandgeneticadaptiveresponses AT andreaschiocchetti crisprcas9mediatededitingofactbininducedpluripotentstemcellsamodelforinvestigatinghumanactblossoffunctionandgeneticadaptiveresponses AT andrearossi crisprcas9mediatededitingofactbininducedpluripotentstemcellsamodelforinvestigatinghumanactblossoffunctionandgeneticadaptiveresponses |