Single-Cell RNA Sequencing of Hematopoietic Stem and Progenitor Cells Treated with Gemcitabine and Carboplatin
Treatments that include gemcitabine and carboplatin induce dose-limiting myelosuppression. The understanding of how human bone marrow is affected on a transcriptional level leading to the development of myelosuppression is required for the implementation of personalized treatments in the future. In...
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MDPI AG
2020-05-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/11/5/549 |
| _version_ | 1797568020640432128 |
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| author | Niclas Björn Ingrid Jakobsen Kourosh Lotfi Henrik Gréen |
| author_facet | Niclas Björn Ingrid Jakobsen Kourosh Lotfi Henrik Gréen |
| author_sort | Niclas Björn |
| collection | DOAJ |
| description | Treatments that include gemcitabine and carboplatin induce dose-limiting myelosuppression. The understanding of how human bone marrow is affected on a transcriptional level leading to the development of myelosuppression is required for the implementation of personalized treatments in the future. In this study, we treated human hematopoietic stem and progenitor cells (HSPCs) harvested from a patient with chronic myelogenous leukemia (CML) with gemcitabine/carboplatin. Thereafter, scRNA-seq was performed to distinguish transcriptional effects induced by gemcitabine/carboplatin. Gene expression was calculated and evaluated among cells within and between samples compared to untreated cells. Cell cycle analysis showed that the treatments effectively decrease cell proliferation, indicated by the proportion of cells in the G2M-phase dropping from 35% in untreated cells to 14.3% in treated cells. Clustering and t-SNE showed that cells within samples and between treated and untreated samples were affected differently. Enrichment analysis of differentially expressed genes showed that the treatments influence KEGG pathways and Gene Ontologies related to myeloid cell proliferation/differentiation, immune response, cancer, and the cell cycle. The present study shows the feasibility of using scRNA-seq and chemotherapy-treated HSPCs to find genes, pathways, and biological processes affected among and between treated and untreated cells. This indicates the possible gains of using single-cell toxicity studies for personalized medicine. |
| first_indexed | 2024-03-10T19:50:27Z |
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| id | doaj.art-41ce8b508fc84908a21e59d8f1f03861 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T19:50:27Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-41ce8b508fc84908a21e59d8f1f038612023-11-20T00:25:09ZengMDPI AGGenes2073-44252020-05-0111554910.3390/genes11050549Single-Cell RNA Sequencing of Hematopoietic Stem and Progenitor Cells Treated with Gemcitabine and CarboplatinNiclas Björn0Ingrid Jakobsen1Kourosh Lotfi2Henrik Gréen3Clinical Pharmacology, Division of Drug Research, Department of Biomedical and Clinical Sciences, Linköping University, 581 85 Linköping, SwedenClinical Pharmacology, Division of Drug Research, Department of Biomedical and Clinical Sciences, Linköping University, 581 85 Linköping, SwedenClinical Pharmacology, Division of Drug Research, Department of Biomedical and Clinical Sciences, Linköping University, 581 85 Linköping, SwedenClinical Pharmacology, Division of Drug Research, Department of Biomedical and Clinical Sciences, Linköping University, 581 85 Linköping, SwedenTreatments that include gemcitabine and carboplatin induce dose-limiting myelosuppression. The understanding of how human bone marrow is affected on a transcriptional level leading to the development of myelosuppression is required for the implementation of personalized treatments in the future. In this study, we treated human hematopoietic stem and progenitor cells (HSPCs) harvested from a patient with chronic myelogenous leukemia (CML) with gemcitabine/carboplatin. Thereafter, scRNA-seq was performed to distinguish transcriptional effects induced by gemcitabine/carboplatin. Gene expression was calculated and evaluated among cells within and between samples compared to untreated cells. Cell cycle analysis showed that the treatments effectively decrease cell proliferation, indicated by the proportion of cells in the G2M-phase dropping from 35% in untreated cells to 14.3% in treated cells. Clustering and t-SNE showed that cells within samples and between treated and untreated samples were affected differently. Enrichment analysis of differentially expressed genes showed that the treatments influence KEGG pathways and Gene Ontologies related to myeloid cell proliferation/differentiation, immune response, cancer, and the cell cycle. The present study shows the feasibility of using scRNA-seq and chemotherapy-treated HSPCs to find genes, pathways, and biological processes affected among and between treated and untreated cells. This indicates the possible gains of using single-cell toxicity studies for personalized medicine.https://www.mdpi.com/2073-4425/11/5/549hematopoietic stem and progenitor cellssingle-cell RNA sequencinggemcitabinecarboplatinmyelosuppressiontoxicity |
| spellingShingle | Niclas Björn Ingrid Jakobsen Kourosh Lotfi Henrik Gréen Single-Cell RNA Sequencing of Hematopoietic Stem and Progenitor Cells Treated with Gemcitabine and Carboplatin Genes hematopoietic stem and progenitor cells single-cell RNA sequencing gemcitabine carboplatin myelosuppression toxicity |
| title | Single-Cell RNA Sequencing of Hematopoietic Stem and Progenitor Cells Treated with Gemcitabine and Carboplatin |
| title_full | Single-Cell RNA Sequencing of Hematopoietic Stem and Progenitor Cells Treated with Gemcitabine and Carboplatin |
| title_fullStr | Single-Cell RNA Sequencing of Hematopoietic Stem and Progenitor Cells Treated with Gemcitabine and Carboplatin |
| title_full_unstemmed | Single-Cell RNA Sequencing of Hematopoietic Stem and Progenitor Cells Treated with Gemcitabine and Carboplatin |
| title_short | Single-Cell RNA Sequencing of Hematopoietic Stem and Progenitor Cells Treated with Gemcitabine and Carboplatin |
| title_sort | single cell rna sequencing of hematopoietic stem and progenitor cells treated with gemcitabine and carboplatin |
| topic | hematopoietic stem and progenitor cells single-cell RNA sequencing gemcitabine carboplatin myelosuppression toxicity |
| url | https://www.mdpi.com/2073-4425/11/5/549 |
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