Differential gene expression analysis identified determinants of cell fate plasticity during radiation-induced regeneration in Drosophila.
Ionizing radiation (IR) is used to treat half of all cancer patients because of its ability to kill cells. IR, however, can induce stem cell-like properties in non-stem cancer cells, potentiating tumor regrowth and reduced therapeutic success. We identified previously a subpopulation of cells in Dro...
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009989&type=printable |
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| author | Michelle Ledru Caitlin A Clark Jeremy Brown Shilpi Verghese Sarah Ferrara Andrew Goodspeed Tin Tin Su |
| author_facet | Michelle Ledru Caitlin A Clark Jeremy Brown Shilpi Verghese Sarah Ferrara Andrew Goodspeed Tin Tin Su |
| author_sort | Michelle Ledru |
| collection | DOAJ |
| description | Ionizing radiation (IR) is used to treat half of all cancer patients because of its ability to kill cells. IR, however, can induce stem cell-like properties in non-stem cancer cells, potentiating tumor regrowth and reduced therapeutic success. We identified previously a subpopulation of cells in Drosophila larval wing discs that exhibit IR-induced stem cell-like properties. These cells reside in the future wing hinge, are resistant to IR-induced apoptosis, and are capable of translocating, changing fate, and participating in regenerating the pouch that suffers more IR-induced apoptosis. We used here a combination of lineage tracing, FACS-sorting of cells that change fate, genome-wide RNAseq, and functional testing of 42 genes, to identify two key changes that are required cell-autonomously for IR-induced hinge-to-pouch fate change: (1) repression of hinge determinants Wg (Drosophila Wnt1) and conserved zinc-finger transcription factor Zfh2 and (2) upregulation of three ribosome biogenesis factors. Additional data indicate a role for Myc, a transcriptional activator of ribosome biogenesis genes, in the process. These results provide a molecular understanding of IR-induced cell fate plasticity that may be leveraged to improve radiation therapy. |
| format | Article |
| id | doaj-art-2a4c36b97a074b89955ab982f506cbee |
| institution | DOAJ |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-2a4c36b97a074b89955ab982f506cbee2025-08-20T03:15:43ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042022-01-01181e100998910.1371/journal.pgen.1009989Differential gene expression analysis identified determinants of cell fate plasticity during radiation-induced regeneration in Drosophila.Michelle LedruCaitlin A ClarkJeremy BrownShilpi VergheseSarah FerraraAndrew GoodspeedTin Tin SuIonizing radiation (IR) is used to treat half of all cancer patients because of its ability to kill cells. IR, however, can induce stem cell-like properties in non-stem cancer cells, potentiating tumor regrowth and reduced therapeutic success. We identified previously a subpopulation of cells in Drosophila larval wing discs that exhibit IR-induced stem cell-like properties. These cells reside in the future wing hinge, are resistant to IR-induced apoptosis, and are capable of translocating, changing fate, and participating in regenerating the pouch that suffers more IR-induced apoptosis. We used here a combination of lineage tracing, FACS-sorting of cells that change fate, genome-wide RNAseq, and functional testing of 42 genes, to identify two key changes that are required cell-autonomously for IR-induced hinge-to-pouch fate change: (1) repression of hinge determinants Wg (Drosophila Wnt1) and conserved zinc-finger transcription factor Zfh2 and (2) upregulation of three ribosome biogenesis factors. Additional data indicate a role for Myc, a transcriptional activator of ribosome biogenesis genes, in the process. These results provide a molecular understanding of IR-induced cell fate plasticity that may be leveraged to improve radiation therapy.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009989&type=printable |
| spellingShingle | Michelle Ledru Caitlin A Clark Jeremy Brown Shilpi Verghese Sarah Ferrara Andrew Goodspeed Tin Tin Su Differential gene expression analysis identified determinants of cell fate plasticity during radiation-induced regeneration in Drosophila. PLoS Genetics |
| title | Differential gene expression analysis identified determinants of cell fate plasticity during radiation-induced regeneration in Drosophila. |
| title_full | Differential gene expression analysis identified determinants of cell fate plasticity during radiation-induced regeneration in Drosophila. |
| title_fullStr | Differential gene expression analysis identified determinants of cell fate plasticity during radiation-induced regeneration in Drosophila. |
| title_full_unstemmed | Differential gene expression analysis identified determinants of cell fate plasticity during radiation-induced regeneration in Drosophila. |
| title_short | Differential gene expression analysis identified determinants of cell fate plasticity during radiation-induced regeneration in Drosophila. |
| title_sort | differential gene expression analysis identified determinants of cell fate plasticity during radiation induced regeneration in drosophila |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009989&type=printable |
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