Human embryoid bodies as a novel system for genomic studies of functionally diverse cell types
Practically all studies of gene expression in humans to date have been performed in a relatively small number of adult tissues. Gene regulation is highly dynamic and context-dependent. In order to better understand the connection between gene regulation and complex phenotypes, including disease, we...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-02-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/71361 |
| _version_ | 1811201583477686272 |
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| author | Katherine Rhodes Kenneth A Barr Joshua M Popp Benjamin J Strober Alexis Battle Yoav Gilad |
| author_facet | Katherine Rhodes Kenneth A Barr Joshua M Popp Benjamin J Strober Alexis Battle Yoav Gilad |
| author_sort | Katherine Rhodes |
| collection | DOAJ |
| description | Practically all studies of gene expression in humans to date have been performed in a relatively small number of adult tissues. Gene regulation is highly dynamic and context-dependent. In order to better understand the connection between gene regulation and complex phenotypes, including disease, we need to be able to study gene expression in more cell types, tissues, and states that are relevant to human phenotypes. In particular, we need to characterize gene expression in early development cell types, as mutations that affect developmental processes may be of particular relevance to complex traits. To address this challenge, we propose to use embryoid bodies (EBs), which are organoids that contain a multitude of cell types in dynamic states. EBs provide a system in which one can study dynamic regulatory processes at an unprecedentedly high resolution. To explore the utility of EBs, we systematically explored cellular and gene expression heterogeneity in EBs from multiple individuals. We characterized the various cell types that arise from EBs, the extent to which they recapitulate gene expression in vivo, and the relative contribution of technical and biological factors to variability in gene expression, cell composition, and differentiation efficiency. Our results highlight the utility of EBs as a new model system for mapping dynamic inter-individual regulatory differences in a large variety of cell types. |
| first_indexed | 2024-04-12T02:24:05Z |
| format | Article |
| id | doaj.art-28b87cc3cb934093b19eb1451ef1e52a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:24:05Z |
| publishDate | 2022-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-28b87cc3cb934093b19eb1451ef1e52a2022-12-22T03:52:03ZengeLife Sciences Publications LtdeLife2050-084X2022-02-011110.7554/eLife.71361Human embryoid bodies as a novel system for genomic studies of functionally diverse cell typesKatherine Rhodes0https://orcid.org/0000-0002-0631-3994Kenneth A Barr1https://orcid.org/0000-0002-0769-7053Joshua M Popp2Benjamin J Strober3Alexis Battle4https://orcid.org/0000-0002-5287-627XYoav Gilad5https://orcid.org/0000-0001-8284-8926Department of Medicine, University of Chicago, Chicago, United StatesDepartment of Medicine, University of Chicago, Chicago, United StatesDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, United StatesDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, United StatesDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, United States; Department of Computer Science, Johns Hopkins University, Baltimore, United States; Department of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland, United StatesDepartment of Medicine, University of Chicago, Chicago, United StatesPractically all studies of gene expression in humans to date have been performed in a relatively small number of adult tissues. Gene regulation is highly dynamic and context-dependent. In order to better understand the connection between gene regulation and complex phenotypes, including disease, we need to be able to study gene expression in more cell types, tissues, and states that are relevant to human phenotypes. In particular, we need to characterize gene expression in early development cell types, as mutations that affect developmental processes may be of particular relevance to complex traits. To address this challenge, we propose to use embryoid bodies (EBs), which are organoids that contain a multitude of cell types in dynamic states. EBs provide a system in which one can study dynamic regulatory processes at an unprecedentedly high resolution. To explore the utility of EBs, we systematically explored cellular and gene expression heterogeneity in EBs from multiple individuals. We characterized the various cell types that arise from EBs, the extent to which they recapitulate gene expression in vivo, and the relative contribution of technical and biological factors to variability in gene expression, cell composition, and differentiation efficiency. Our results highlight the utility of EBs as a new model system for mapping dynamic inter-individual regulatory differences in a large variety of cell types.https://elifesciences.org/articles/71361iPSCembryoid bodiessingle cellscRNA-seq |
| spellingShingle | Katherine Rhodes Kenneth A Barr Joshua M Popp Benjamin J Strober Alexis Battle Yoav Gilad Human embryoid bodies as a novel system for genomic studies of functionally diverse cell types eLife iPSC embryoid bodies single cell scRNA-seq |
| title | Human embryoid bodies as a novel system for genomic studies of functionally diverse cell types |
| title_full | Human embryoid bodies as a novel system for genomic studies of functionally diverse cell types |
| title_fullStr | Human embryoid bodies as a novel system for genomic studies of functionally diverse cell types |
| title_full_unstemmed | Human embryoid bodies as a novel system for genomic studies of functionally diverse cell types |
| title_short | Human embryoid bodies as a novel system for genomic studies of functionally diverse cell types |
| title_sort | human embryoid bodies as a novel system for genomic studies of functionally diverse cell types |
| topic | iPSC embryoid bodies single cell scRNA-seq |
| url | https://elifesciences.org/articles/71361 |
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