Cellular Heterogeneity and Cooperativity in Glioma Persister Cells Under Temozolomide Treatment
We have observed a drug-tolerant/persister state in a human glioblastoma (GBM) cell line after exposure to temozolomide, the standard-of-care chemotherapeutic agent for GBM. We used a multicolor lentiviral genetic barcode labeling to follow cell population evolution during temozolomide treatment. We...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.835273/full |
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| author | Marion Rabé Lucie Fonteneau Lisa Oliver Lisa Oliver Alvaro Morales-Molina Camille Jubelin Camille Jubelin Javier Garcia-Castro Dominique Heymann Dominique Heymann Catherine Gratas Catherine Gratas François M. Vallette François M. Vallette |
| author_facet | Marion Rabé Lucie Fonteneau Lisa Oliver Lisa Oliver Alvaro Morales-Molina Camille Jubelin Camille Jubelin Javier Garcia-Castro Dominique Heymann Dominique Heymann Catherine Gratas Catherine Gratas François M. Vallette François M. Vallette |
| author_sort | Marion Rabé |
| collection | DOAJ |
| description | We have observed a drug-tolerant/persister state in a human glioblastoma (GBM) cell line after exposure to temozolomide, the standard-of-care chemotherapeutic agent for GBM. We used a multicolor lentiviral genetic barcode labeling to follow cell population evolution during temozolomide treatment. We observed no change in the distribution of the different colored populations of cells in persister or resistant cells suggesting that pre-existing minor subpopulations, which would be expected to be restricted to a single color, were not amplified/selected during the response to the drug. We have previously identified four genes (CHI3L1, FAT2, KLK5, and HB-EGF) that were over-expressed during the persister stage. Single-cell analysis of these four genes indicated that they were expressed in different individual cells ruling out the existence of a single persister-specific clone but suggesting rather a global answer. Even so, the transitory silencing of CHI3L1, FAT2, or KLK5 influenced the expression of the other three genes and the survival of U251 cells in absence of temozolomide. Since proteins encoded by the four genes are all localized in the extracellular matrix or interact within the extracellular compartment, we propose that cellular interactions and communications are important during the persister stage before the acquisition of chemo-resistance. Thus, persisters might be a new therapeutically relevant target in GBM. |
| first_indexed | 2024-12-12T09:00:18Z |
| format | Article |
| id | doaj.art-af10a72ecb07478da8fef7c1d545335e |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-12T09:00:18Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-af10a72ecb07478da8fef7c1d545335e2022-12-22T00:29:51ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-05-011010.3389/fcell.2022.835273835273Cellular Heterogeneity and Cooperativity in Glioma Persister Cells Under Temozolomide TreatmentMarion Rabé0Lucie Fonteneau1Lisa Oliver2Lisa Oliver3Alvaro Morales-Molina4Camille Jubelin5Camille Jubelin6Javier Garcia-Castro7Dominique Heymann8Dominique Heymann9Catherine Gratas10Catherine Gratas11François M. Vallette12François M. Vallette13Université de Nantes, INSERM U1232, CRCINA, Nantes, FranceUniversité de Nantes, INSERM U1232, CRCINA, Nantes, FranceUniversité de Nantes, INSERM U1232, CRCINA, Nantes, FranceCHU Nantes, Nantes, FranceCellular Biotechnology Unit, Instituto de Salud Carlos III, Madrid, SpainUniversité de Nantes, INSERM U1232, CRCINA, Nantes, FranceInstitut de Cancérologie de l'Ouest-St Herblain, Saint-Herblain, FranceCellular Biotechnology Unit, Instituto de Salud Carlos III, Madrid, SpainUniversité de Nantes, INSERM U1232, CRCINA, Nantes, FranceInstitut de Cancérologie de l'Ouest-St Herblain, Saint-Herblain, FranceUniversité de Nantes, INSERM U1232, CRCINA, Nantes, FranceCHU Nantes, Nantes, FranceUniversité de Nantes, INSERM U1232, CRCINA, Nantes, FranceInstitut de Cancérologie de l'Ouest-St Herblain, Saint-Herblain, FranceWe have observed a drug-tolerant/persister state in a human glioblastoma (GBM) cell line after exposure to temozolomide, the standard-of-care chemotherapeutic agent for GBM. We used a multicolor lentiviral genetic barcode labeling to follow cell population evolution during temozolomide treatment. We observed no change in the distribution of the different colored populations of cells in persister or resistant cells suggesting that pre-existing minor subpopulations, which would be expected to be restricted to a single color, were not amplified/selected during the response to the drug. We have previously identified four genes (CHI3L1, FAT2, KLK5, and HB-EGF) that were over-expressed during the persister stage. Single-cell analysis of these four genes indicated that they were expressed in different individual cells ruling out the existence of a single persister-specific clone but suggesting rather a global answer. Even so, the transitory silencing of CHI3L1, FAT2, or KLK5 influenced the expression of the other three genes and the survival of U251 cells in absence of temozolomide. Since proteins encoded by the four genes are all localized in the extracellular matrix or interact within the extracellular compartment, we propose that cellular interactions and communications are important during the persister stage before the acquisition of chemo-resistance. Thus, persisters might be a new therapeutically relevant target in GBM.https://www.frontiersin.org/articles/10.3389/fcell.2022.835273/fullgliomapersistersclonesresistancebarcoding |
| spellingShingle | Marion Rabé Lucie Fonteneau Lisa Oliver Lisa Oliver Alvaro Morales-Molina Camille Jubelin Camille Jubelin Javier Garcia-Castro Dominique Heymann Dominique Heymann Catherine Gratas Catherine Gratas François M. Vallette François M. Vallette Cellular Heterogeneity and Cooperativity in Glioma Persister Cells Under Temozolomide Treatment Frontiers in Cell and Developmental Biology glioma persisters clones resistance barcoding |
| title | Cellular Heterogeneity and Cooperativity in Glioma Persister Cells Under Temozolomide Treatment |
| title_full | Cellular Heterogeneity and Cooperativity in Glioma Persister Cells Under Temozolomide Treatment |
| title_fullStr | Cellular Heterogeneity and Cooperativity in Glioma Persister Cells Under Temozolomide Treatment |
| title_full_unstemmed | Cellular Heterogeneity and Cooperativity in Glioma Persister Cells Under Temozolomide Treatment |
| title_short | Cellular Heterogeneity and Cooperativity in Glioma Persister Cells Under Temozolomide Treatment |
| title_sort | cellular heterogeneity and cooperativity in glioma persister cells under temozolomide treatment |
| topic | glioma persisters clones resistance barcoding |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.835273/full |
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