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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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Autores principales: Björn, Niclas, Jakobsen, Ingrid, Lotfi, Kourosh, Gréen, Henrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288450/
https://www.ncbi.nlm.nih.gov/pubmed/32422951
http://dx.doi.org/10.3390/genes11050549
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author Björn, Niclas
Jakobsen, Ingrid
Lotfi, Kourosh
Gréen, Henrik
author_facet Björn, Niclas
Jakobsen, Ingrid
Lotfi, Kourosh
Gréen, Henrik
author_sort Björn, Niclas
collection PubMed
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.
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spelling pubmed-72884502020-06-17 Single-Cell RNA Sequencing of Hematopoietic Stem and Progenitor Cells Treated with Gemcitabine and Carboplatin Björn, Niclas Jakobsen, Ingrid Lotfi, Kourosh Gréen, Henrik Genes (Basel) Article 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. MDPI 2020-05-14 /pmc/articles/PMC7288450/ /pubmed/32422951 http://dx.doi.org/10.3390/genes11050549 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Björn, Niclas
Jakobsen, Ingrid
Lotfi, Kourosh
Gréen, Henrik
Single-Cell RNA Sequencing of Hematopoietic Stem and Progenitor Cells Treated with Gemcitabine and Carboplatin
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288450/
https://www.ncbi.nlm.nih.gov/pubmed/32422951
http://dx.doi.org/10.3390/genes11050549
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