Human cellular model systems of β-thalassemia enable in-depth analysis of disease phenotype
Abstract β-thalassemia is a prevalent genetic disorder causing severe anemia due to defective erythropoiesis, with few treatment options. Studying the underlying molecular defects is impeded by paucity of suitable patient material. In this study we create human disease cellular model systems for β-t...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41961-9 |
| _version_ | 1797558244706615296 |
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| author | Deborah E. Daniels Ivan Ferrer-Vicens Joseph Hawksworth Tatyana N. Andrienko Elizabeth M. Finnie Natalie S. Bretherton Daniel C. J. Ferguson A. Sofia. F. Oliveira Jenn-Yeu A. Szeto Marieangela C. Wilson John N. Brewin Jan Frayne |
| author_facet | Deborah E. Daniels Ivan Ferrer-Vicens Joseph Hawksworth Tatyana N. Andrienko Elizabeth M. Finnie Natalie S. Bretherton Daniel C. J. Ferguson A. Sofia. F. Oliveira Jenn-Yeu A. Szeto Marieangela C. Wilson John N. Brewin Jan Frayne |
| author_sort | Deborah E. Daniels |
| collection | DOAJ |
| description | Abstract β-thalassemia is a prevalent genetic disorder causing severe anemia due to defective erythropoiesis, with few treatment options. Studying the underlying molecular defects is impeded by paucity of suitable patient material. In this study we create human disease cellular model systems for β-thalassemia by gene editing the erythroid line BEL-A, which accurately recapitulate the phenotype of patient erythroid cells. We also develop a high throughput compatible fluorometric-based assay for evaluating severity of disease phenotype and utilize the assay to demonstrate that the lines respond appropriately to verified reagents. We next use the lines to perform extensive analysis of the altered molecular mechanisms in β-thalassemia erythroid cells, revealing upregulation of a wide range of biological pathways and processes along with potential novel targets for therapeutic investigation. Overall, the lines provide a sustainable supply of disease cells as research tools for identifying therapeutic targets and as screening platforms for new drugs and reagents. |
| first_indexed | 2024-03-10T17:27:36Z |
| format | Article |
| id | doaj.art-9939683767224f40b2a842f9297fb596 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:27:36Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-9939683767224f40b2a842f9297fb5962023-11-20T10:06:56ZengNature PortfolioNature Communications2041-17232023-10-0114111410.1038/s41467-023-41961-9Human cellular model systems of β-thalassemia enable in-depth analysis of disease phenotypeDeborah E. Daniels0Ivan Ferrer-Vicens1Joseph Hawksworth2Tatyana N. Andrienko3Elizabeth M. Finnie4Natalie S. Bretherton5Daniel C. J. Ferguson6A. Sofia. F. Oliveira7Jenn-Yeu A. Szeto8Marieangela C. Wilson9John N. Brewin10Jan Frayne11School of Biochemistry, University of BristolSchool of Biochemistry, University of BristolSchool of Biochemistry, University of BristolSchool of Biochemistry, University of BristolSchool of Biochemistry, University of BristolSchool of Biochemistry, University of BristolSchool of Biochemistry, University of BristolSchool of Biochemistry, University of BristolSchool of Biochemistry, University of BristolSchool of Biochemistry, University of BristolHaematology Department, King’s college Hospital NHS FoundationSchool of Biochemistry, University of BristolAbstract β-thalassemia is a prevalent genetic disorder causing severe anemia due to defective erythropoiesis, with few treatment options. Studying the underlying molecular defects is impeded by paucity of suitable patient material. In this study we create human disease cellular model systems for β-thalassemia by gene editing the erythroid line BEL-A, which accurately recapitulate the phenotype of patient erythroid cells. We also develop a high throughput compatible fluorometric-based assay for evaluating severity of disease phenotype and utilize the assay to demonstrate that the lines respond appropriately to verified reagents. We next use the lines to perform extensive analysis of the altered molecular mechanisms in β-thalassemia erythroid cells, revealing upregulation of a wide range of biological pathways and processes along with potential novel targets for therapeutic investigation. Overall, the lines provide a sustainable supply of disease cells as research tools for identifying therapeutic targets and as screening platforms for new drugs and reagents.https://doi.org/10.1038/s41467-023-41961-9 |
| spellingShingle | Deborah E. Daniels Ivan Ferrer-Vicens Joseph Hawksworth Tatyana N. Andrienko Elizabeth M. Finnie Natalie S. Bretherton Daniel C. J. Ferguson A. Sofia. F. Oliveira Jenn-Yeu A. Szeto Marieangela C. Wilson John N. Brewin Jan Frayne Human cellular model systems of β-thalassemia enable in-depth analysis of disease phenotype Nature Communications |
| title | Human cellular model systems of β-thalassemia enable in-depth analysis of disease phenotype |
| title_full | Human cellular model systems of β-thalassemia enable in-depth analysis of disease phenotype |
| title_fullStr | Human cellular model systems of β-thalassemia enable in-depth analysis of disease phenotype |
| title_full_unstemmed | Human cellular model systems of β-thalassemia enable in-depth analysis of disease phenotype |
| title_short | Human cellular model systems of β-thalassemia enable in-depth analysis of disease phenotype |
| title_sort | human cellular model systems of β thalassemia enable in depth analysis of disease phenotype |
| url | https://doi.org/10.1038/s41467-023-41961-9 |
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