Single-cell transcriptional analysis of normal, aberrant, and malignant hematopoiesis in zebrafish
| Autor: | Ravi Mylvaganam, Qin Tang, Jeffrey A. Yoder, Riadh Lobbardi, Mauricio Cortes, Ruslan I. Sadreyev, Finola E. Moore, Esha Jain, Melissa Kasheta, Jessica S. Blackburn, Craig J. Ceol, Elaine G. Garcia, John C. Moore, Amaris J. Garcia, David M. Langenau, Christina C. Luo, Aleksey Molodtsov, Trista E. North |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Myeloid Transcription Genetic T cell T-Lymphocytes Immunology Mutation Missense Article Blood cell 03 medical and health sciences 0302 clinical medicine 0502 economics and business medicine Immunology and Allergy Cytotoxic T cell Animals 050207 economics Progenitor cell Zebrafish Research Articles 050208 finance biology 05 social sciences Cell Biology Precursor Cell Lymphoblastic Leukemia-Lymphoma Zebrafish Proteins biology.organism_classification Hematopoietic Stem Cells Molecular biology 3. Good health Hematopoiesis DNA-Binding Proteins Killer Cells Natural Haematopoiesis 030104 developmental biology medicine.anatomical_structure Amino Acid Substitution 030220 oncology & carcinogenesis Neoplastic Stem Cells Stem cell |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | Moore et al. reports the first single-cell gene expression analysis in zebrafish blood to distinguish major blood lineages, identify new cell types, and delineate heterogeneity in T cell leukemia. Hematopoiesis culminates in the production of functionally heterogeneous blood cell types. In zebrafish, the lack of cell surface antibodies has compelled researchers to use fluorescent transgenic reporter lines to label specific blood cell fractions. However, these approaches are limited by the availability of transgenic lines and fluorescent protein combinations that can be distinguished. Here, we have transcriptionally profiled single hematopoietic cells from zebrafish to define erythroid, myeloid, B, and T cell lineages. We also used our approach to identify hematopoietic stem and progenitor cells and a novel NK-lysin 4+ cell type, representing a putative cytotoxic T/NK cell. Our platform also quantified hematopoietic defects in rag2E450fs mutant fish and showed that these fish have reduced T cells with a subsequent expansion of NK-lysin 4+ cells and myeloid cells. These data suggest compensatory regulation of the innate immune system in rag2E450fs mutant zebrafish. Finally, analysis of Myc-induced T cell acute lymphoblastic leukemia showed that cells are arrested at the CD4+/CD8+ cortical thymocyte stage and that a subset of leukemia cells inappropriately reexpress stem cell genes, including bmi1 and cmyb. In total, our experiments provide new tools and biological insights into single-cell heterogeneity found in zebrafish blood and leukemia. |
| Databáze: | OpenAIRE |
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