Modeling Blast Crisis Using Mutagenized Chronic Myeloid Leukemia-Derived Induced Pluripotent Stem Cells (iPSCs)
Purpose: To model CML progression in vitro and generate a blast crisis (BC-CML) model in vitro in order to identify new targets. Methods: Three different CML-derived iPSC lines were mutagenized with the alkylating agent ENU on a daily basis for 60 days. Cells were analyzed at D12 of hematopoietic di...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/4/598 |
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| author | Jusuf Imeri Christophe Desterke Paul Marcoux Gladys Telliam Safa Sanekli Sylvain Barreau Yucel Erbilgin Theodoros Latsis Patricia Hugues Nathalie Sorel Emilie Cayssials Jean-Claude Chomel Annelise Bennaceur-Griscelli Ali G. Turhan |
| author_facet | Jusuf Imeri Christophe Desterke Paul Marcoux Gladys Telliam Safa Sanekli Sylvain Barreau Yucel Erbilgin Theodoros Latsis Patricia Hugues Nathalie Sorel Emilie Cayssials Jean-Claude Chomel Annelise Bennaceur-Griscelli Ali G. Turhan |
| author_sort | Jusuf Imeri |
| collection | DOAJ |
| description | Purpose: To model CML progression in vitro and generate a blast crisis (BC-CML) model in vitro in order to identify new targets. Methods: Three different CML-derived iPSC lines were mutagenized with the alkylating agent ENU on a daily basis for 60 days. Cells were analyzed at D12 of hematopoietic differentiation for their phenotype, clonogenicity, and transcriptomic profile. Single-cell RNA-Seq analysis has been performed at three different time points during hematopoietic differentiation in ENU-treated and untreated cells. Results: One of the CML-iPSCs, compared to its non-mutagenized counterpart, generated myeloid blasts after hematopoietic differentiation, exhibiting monoblastic patterns and expression of cMPO, CD45, CD34, CD33, and CD13. Single-cell transcriptomics revealed a delay of differentiation in the mutated condition as compared to the control with increased levels of <i>MSX1</i> (mesodermal marker) and a decrease in <i>CD45</i> and <i>CD41</i>. Bulk transcriptomics analyzed along with the GSE4170 GEO dataset reveal a significant overlap between ENU-treated cells and primary BC cells. Among overexpressed genes, <i>CD25</i> was identified, and its relevance was confirmed in a cohort of CML patients. Conclusions: iPSCs are a valuable tool to model CML progression and to identify new targets. Here, we show the relevance of CD25 identified in the iPSC model as a marker of CML progression. |
| first_indexed | 2024-03-11T09:00:53Z |
| format | Article |
| id | doaj.art-68ca13524a4b4e71bf4f8c1f1278d1db |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T09:00:53Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-68ca13524a4b4e71bf4f8c1f1278d1db2023-11-16T19:44:35ZengMDPI AGCells2073-44092023-02-0112459810.3390/cells12040598Modeling Blast Crisis Using Mutagenized Chronic Myeloid Leukemia-Derived Induced Pluripotent Stem Cells (iPSCs)Jusuf Imeri0Christophe Desterke1Paul Marcoux2Gladys Telliam3Safa Sanekli4Sylvain Barreau5Yucel Erbilgin6Theodoros Latsis7Patricia Hugues8Nathalie Sorel9Emilie Cayssials10Jean-Claude Chomel11Annelise Bennaceur-Griscelli12Ali G. Turhan13INSERM UMR-S-1310, Université Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Université Paris Saclay, 94800 Villejuif, FranceINSERM UMR-S-1310, Université Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Université Paris Saclay, 94800 Villejuif, FranceINSERM UMR-S-1310, Université Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Université Paris Saclay, 94800 Villejuif, FranceINSERM UMR-S-1310, Université Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Université Paris Saclay, 94800 Villejuif, FranceINSERM UMR-S-1310, Université Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Université Paris Saclay, 94800 Villejuif, FranceINSERM UMR-S-1310, Université Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Université Paris Saclay, 94800 Villejuif, FranceINSERM UMR-S-1310, Université Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Université Paris Saclay, 94800 Villejuif, FranceINSERM UMR-S-1310, Université Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Université Paris Saclay, 94800 Villejuif, FranceINSERM UMR-S-1310, Université Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Université Paris Saclay, 94800 Villejuif, FranceINSERM UMR-S-1310, Université Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Université Paris Saclay, 94800 Villejuif, FranceService d’Oncologie Hématologique et Thérapie Cellulaire, CHU de Poitiers, 86021 Poitiers, FranceINSERM UMR-S-1310, Université Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Université Paris Saclay, 94800 Villejuif, FranceINSERM UMR-S-1310, Université Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Université Paris Saclay, 94800 Villejuif, FranceINSERM UMR-S-1310, Université Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Université Paris Saclay, 94800 Villejuif, FrancePurpose: To model CML progression in vitro and generate a blast crisis (BC-CML) model in vitro in order to identify new targets. Methods: Three different CML-derived iPSC lines were mutagenized with the alkylating agent ENU on a daily basis for 60 days. Cells were analyzed at D12 of hematopoietic differentiation for their phenotype, clonogenicity, and transcriptomic profile. Single-cell RNA-Seq analysis has been performed at three different time points during hematopoietic differentiation in ENU-treated and untreated cells. Results: One of the CML-iPSCs, compared to its non-mutagenized counterpart, generated myeloid blasts after hematopoietic differentiation, exhibiting monoblastic patterns and expression of cMPO, CD45, CD34, CD33, and CD13. Single-cell transcriptomics revealed a delay of differentiation in the mutated condition as compared to the control with increased levels of <i>MSX1</i> (mesodermal marker) and a decrease in <i>CD45</i> and <i>CD41</i>. Bulk transcriptomics analyzed along with the GSE4170 GEO dataset reveal a significant overlap between ENU-treated cells and primary BC cells. Among overexpressed genes, <i>CD25</i> was identified, and its relevance was confirmed in a cohort of CML patients. Conclusions: iPSCs are a valuable tool to model CML progression and to identify new targets. Here, we show the relevance of CD25 identified in the iPSC model as a marker of CML progression.https://www.mdpi.com/2073-4409/12/4/598iPSCblast crisis CMLCML modelingsingle-cell transcriptomicsCD25 |
| spellingShingle | Jusuf Imeri Christophe Desterke Paul Marcoux Gladys Telliam Safa Sanekli Sylvain Barreau Yucel Erbilgin Theodoros Latsis Patricia Hugues Nathalie Sorel Emilie Cayssials Jean-Claude Chomel Annelise Bennaceur-Griscelli Ali G. Turhan Modeling Blast Crisis Using Mutagenized Chronic Myeloid Leukemia-Derived Induced Pluripotent Stem Cells (iPSCs) Cells iPSC blast crisis CML CML modeling single-cell transcriptomics CD25 |
| title | Modeling Blast Crisis Using Mutagenized Chronic Myeloid Leukemia-Derived Induced Pluripotent Stem Cells (iPSCs) |
| title_full | Modeling Blast Crisis Using Mutagenized Chronic Myeloid Leukemia-Derived Induced Pluripotent Stem Cells (iPSCs) |
| title_fullStr | Modeling Blast Crisis Using Mutagenized Chronic Myeloid Leukemia-Derived Induced Pluripotent Stem Cells (iPSCs) |
| title_full_unstemmed | Modeling Blast Crisis Using Mutagenized Chronic Myeloid Leukemia-Derived Induced Pluripotent Stem Cells (iPSCs) |
| title_short | Modeling Blast Crisis Using Mutagenized Chronic Myeloid Leukemia-Derived Induced Pluripotent Stem Cells (iPSCs) |
| title_sort | modeling blast crisis using mutagenized chronic myeloid leukemia derived induced pluripotent stem cells ipscs |
| topic | iPSC blast crisis CML CML modeling single-cell transcriptomics CD25 |
| url | https://www.mdpi.com/2073-4409/12/4/598 |
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