Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity
Acute myeloid leukemia (AML) is a heterogeneous disease that resides within a complex microenvironment, complicating efforts to understand how different cell types contribute to disease progression. We combined single-cell RNA sequencing and genotyping to profile 38,410 cells from 40 bone marrow asp...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Elsevier BV
2020
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| Online Access: | https://hdl.handle.net/1721.1/125158 |
| _version_ | 1826212857212043264 |
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| author | van Galen, Peter Hovestadt, Volker Wadsworth II, Marc H. Hughes, Travis K. Griffin, Gabriel K. Battaglia, Sofia Verga, Julia A. Stephansky, Jason Pastika, Timothy J. Lombardi Story, Jennifer Pinkus, Geraldine S. Pozdnyakova, Olga Galinsky, Ilene Stone, Richard M. Graubert, Timothy A. Shalek, Alex K. Aster, Jon C. Lane, Andrew A. Bernstein, Bradley E. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry van Galen, Peter Hovestadt, Volker Wadsworth II, Marc H. Hughes, Travis K. Griffin, Gabriel K. Battaglia, Sofia Verga, Julia A. Stephansky, Jason Pastika, Timothy J. Lombardi Story, Jennifer Pinkus, Geraldine S. Pozdnyakova, Olga Galinsky, Ilene Stone, Richard M. Graubert, Timothy A. Shalek, Alex K. Aster, Jon C. Lane, Andrew A. Bernstein, Bradley E. |
| author_sort | van Galen, Peter |
| collection | MIT |
| description | Acute myeloid leukemia (AML) is a heterogeneous disease that resides within a complex microenvironment, complicating efforts to understand how different cell types contribute to disease progression. We combined single-cell RNA sequencing and genotyping to profile 38,410 cells from 40 bone marrow aspirates, including 16 AML patients and five healthy donors. We then applied a machine learning classifier to distinguish a spectrum of malignant cell types whose abundances varied between patients and between subclones in the same tumor. Cell type compositions correlated with prototypic genetic lesions, including an association of FLT3-ITD with abundant progenitor-like cells. Primitive AML cells exhibited dysregulated transcriptional programs with co-expression of stemness and myeloid priming genes and had prognostic significance. Differentiated monocyte-like AML cells expressed diverse immunomodulatory genes and suppressed T cell activity in vitro. In conclusion, we provide single-cell technologies and an atlas of AML cell states, regulators, and markers with implications for precision medicine and immune therapies. Video Abstract: A combination of transcriptomics and mutational analyses in single cells from acute myeloid leukemia patients reveals the existence of distinct functional subsets and their associated drivers. |
| first_indexed | 2024-09-23T15:38:55Z |
| format | Article |
| id | mit-1721.1/125158 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:38:55Z |
| publishDate | 2020 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1251582022-09-29T15:16:12Z Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity van Galen, Peter Hovestadt, Volker Wadsworth II, Marc H. Hughes, Travis K. Griffin, Gabriel K. Battaglia, Sofia Verga, Julia A. Stephansky, Jason Pastika, Timothy J. Lombardi Story, Jennifer Pinkus, Geraldine S. Pozdnyakova, Olga Galinsky, Ilene Stone, Richard M. Graubert, Timothy A. Shalek, Alex K. Aster, Jon C. Lane, Andrew A. Bernstein, Bradley E. Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. Institute for Medical Engineering & Science Koch Institute for Integrative Cancer Research at MIT Acute myeloid leukemia (AML) is a heterogeneous disease that resides within a complex microenvironment, complicating efforts to understand how different cell types contribute to disease progression. We combined single-cell RNA sequencing and genotyping to profile 38,410 cells from 40 bone marrow aspirates, including 16 AML patients and five healthy donors. We then applied a machine learning classifier to distinguish a spectrum of malignant cell types whose abundances varied between patients and between subclones in the same tumor. Cell type compositions correlated with prototypic genetic lesions, including an association of FLT3-ITD with abundant progenitor-like cells. Primitive AML cells exhibited dysregulated transcriptional programs with co-expression of stemness and myeloid priming genes and had prognostic significance. Differentiated monocyte-like AML cells expressed diverse immunomodulatory genes and suppressed T cell activity in vitro. In conclusion, we provide single-cell technologies and an atlas of AML cell states, regulators, and markers with implications for precision medicine and immune therapies. Video Abstract: A combination of transcriptomics and mutational analyses in single cells from acute myeloid leukemia patients reveals the existence of distinct functional subsets and their associated drivers. 2020-05-11T19:28:19Z 2020-05-11T19:28:19Z 2019-03 2018-12 2020-03-17T17:17:52Z Article http://purl.org/eprint/type/JournalArticle 0092-8674 https://hdl.handle.net/1721.1/125158 van Galen, Peter et al. "Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity." Cell 176, 6 (March 2019): P1265-1281.e24 © 2019 Elsevier Inc en http://dx.doi.org/10.1016/j.cell.2019.01.031 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | van Galen, Peter Hovestadt, Volker Wadsworth II, Marc H. Hughes, Travis K. Griffin, Gabriel K. Battaglia, Sofia Verga, Julia A. Stephansky, Jason Pastika, Timothy J. Lombardi Story, Jennifer Pinkus, Geraldine S. Pozdnyakova, Olga Galinsky, Ilene Stone, Richard M. Graubert, Timothy A. Shalek, Alex K. Aster, Jon C. Lane, Andrew A. Bernstein, Bradley E. Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity |
| title | Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity |
| title_full | Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity |
| title_fullStr | Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity |
| title_full_unstemmed | Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity |
| title_short | Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity |
| title_sort | single cell rna seq reveals aml hierarchies relevant to disease progression and immunity |
| url | https://hdl.handle.net/1721.1/125158 |
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