A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages
We introduce a microfluidic platform that enables off-chip single-cell RNA-seq after multi-generational lineage tracking under controlled culture conditions. We use this platform to generate whole-transcriptome profiles of primary, activated murine CD8+ T-cell and lymphocytic leukemia cell line line...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2016
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| Online Access: | http://hdl.handle.net/1721.1/101730 https://orcid.org/0000-0002-7380-9594 https://orcid.org/0000-0001-5223-9433 https://orcid.org/0000-0003-3079-5134 https://orcid.org/0000-0001-7604-1333 https://orcid.org/0000-0003-3552-8182 https://orcid.org/0000-0001-7014-3830 https://orcid.org/0000-0001-9939-764X |
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| author | Li, Jennifer W. Genshaft, Alex S. de Riba Borrajo, Jacob Shalek, Alex K. Kimmerling, Robert John Kazer, Samuel Weisgurt Payer, Kristofor Robert Borrajo, Jacob de Riba Blainey, Paul C Irvine, Darrell J Manalis, Scott R Szeto, Gregory Shalek, Alexander K |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Li, Jennifer W. Genshaft, Alex S. de Riba Borrajo, Jacob Shalek, Alex K. Kimmerling, Robert John Kazer, Samuel Weisgurt Payer, Kristofor Robert Borrajo, Jacob de Riba Blainey, Paul C Irvine, Darrell J Manalis, Scott R Szeto, Gregory Shalek, Alexander K |
| author_sort | Li, Jennifer W. |
| collection | MIT |
| description | We introduce a microfluidic platform that enables off-chip single-cell RNA-seq after multi-generational lineage tracking under controlled culture conditions. We use this platform to generate whole-transcriptome profiles of primary, activated murine CD8+ T-cell and lymphocytic leukemia cell line lineages. Here we report that both cell types have greater intra- than inter-lineage transcriptional similarity. For CD8+ T-cells, genes with functional annotation relating to lymphocyte differentiation and function—including Granzyme B—are enriched among the genes that demonstrate greater intra-lineage expression level similarity. Analysis of gene expression covariance with matched measurements of time since division reveals cell type-specific transcriptional signatures that correspond with cell cycle progression. We believe that the ability to directly measure the effects of lineage and cell cycle-dependent transcriptional profiles of single cells will be broadly useful to fields where heterogeneous populations of cells display distinct clonal trajectories, including immunology, cancer, and developmental biology. |
| first_indexed | 2024-09-23T16:59:35Z |
| format | Article |
| id | mit-1721.1/101730 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:59:35Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1017302022-10-03T09:38:46Z A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages Li, Jennifer W. Genshaft, Alex S. de Riba Borrajo, Jacob Shalek, Alex K. Kimmerling, Robert John Kazer, Samuel Weisgurt Payer, Kristofor Robert Borrajo, Jacob de Riba Blainey, Paul C Irvine, Darrell J Manalis, Scott R Szeto, Gregory Shalek, Alexander K Massachusetts Institute of Technology. Institute for Medical Engineering & Science Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. Department of Materials Science and Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Massachusetts Institute of Technology. Microsystems Technology Laboratories Koch Institute for Integrative Cancer Research at MIT Kimmerling, Robert John Szeto, Gregory Lee Li, Jennifer W. Genshaft, Alex S. Kazer, Samuel Weisgurt Payer, Kristofor Robert Borrajo, Jacob de Riba Blainey, Paul C. Irvine, Darrell J. Shalek, Alex Manalis, Scott R. We introduce a microfluidic platform that enables off-chip single-cell RNA-seq after multi-generational lineage tracking under controlled culture conditions. We use this platform to generate whole-transcriptome profiles of primary, activated murine CD8+ T-cell and lymphocytic leukemia cell line lineages. Here we report that both cell types have greater intra- than inter-lineage transcriptional similarity. For CD8+ T-cells, genes with functional annotation relating to lymphocyte differentiation and function—including Granzyme B—are enriched among the genes that demonstrate greater intra-lineage expression level similarity. Analysis of gene expression covariance with matched measurements of time since division reveals cell type-specific transcriptional signatures that correspond with cell cycle progression. We believe that the ability to directly measure the effects of lineage and cell cycle-dependent transcriptional profiles of single cells will be broadly useful to fields where heterogeneous populations of cells display distinct clonal trajectories, including immunology, cancer, and developmental biology. National Institutes of Health (U.S.) (Contract R21AI110787) National Cancer Institute (U.S.). Physical Sciences Oncology Center (U54CA143874) National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051) National Science Foundation (U.S.). Graduate Research Fellowship National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award F32CA1800586) Kinship Foundation. Searle Scholars Program Beckman Young Investigator Program National Institutes of Health (U.S.) (New Innovator Award DP2 OD020839) 2016-03-17T00:53:22Z 2016-03-17T00:53:22Z 2016-01 2015-06 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/101730 Kimmerling, Robert J., Gregory Lee Szeto, Jennifer W. Li, Alex S. Genshaft, Samuel W. Kazer, Kristofor R. Payer, Jacob de Riba Borrajo, et al. “A Microfluidic Platform Enabling Single-Cell RNA-Seq of Multigenerational Lineages.” Nat Comms 7 (January 6, 2016): 10220. https://orcid.org/0000-0002-7380-9594 https://orcid.org/0000-0001-5223-9433 https://orcid.org/0000-0003-3079-5134 https://orcid.org/0000-0001-7604-1333 https://orcid.org/0000-0003-3552-8182 https://orcid.org/0000-0001-7014-3830 https://orcid.org/0000-0001-9939-764X en_US http://dx.doi.org/10.1038/ncomms10220 Nature Communications Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature Publishing Group |
| spellingShingle | Li, Jennifer W. Genshaft, Alex S. de Riba Borrajo, Jacob Shalek, Alex K. Kimmerling, Robert John Kazer, Samuel Weisgurt Payer, Kristofor Robert Borrajo, Jacob de Riba Blainey, Paul C Irvine, Darrell J Manalis, Scott R Szeto, Gregory Shalek, Alexander K A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages |
| title | A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages |
| title_full | A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages |
| title_fullStr | A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages |
| title_full_unstemmed | A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages |
| title_short | A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages |
| title_sort | microfluidic platform enabling single cell rna seq of multigenerational lineages |
| url | http://hdl.handle.net/1721.1/101730 https://orcid.org/0000-0002-7380-9594 https://orcid.org/0000-0001-5223-9433 https://orcid.org/0000-0003-3079-5134 https://orcid.org/0000-0001-7604-1333 https://orcid.org/0000-0003-3552-8182 https://orcid.org/0000-0001-7014-3830 https://orcid.org/0000-0001-9939-764X |
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