Lineage tracing reveals fate bias and transcriptional memory in human B cells
- Creators
- Swift, Michael
- Horns, Felix
- Quake, Stephen R.
Abstract
We combined single-cell transcriptomics and lineage tracing to understand fate choice in human B cells. Using the antibody sequences of B cells, we tracked clones during in vitro differentiation. Clonal analysis revealed a subset of IgM+ B cells which were more proliferative than other B-cell types. Whereas the population of B cells adopted diverse states during differentiation, clones had a restricted set of fates available to them; there were two times more single-fate clones than expected given population-level cell-type diversity. This implicated a molecular memory of initial cell states that was propagated through differentiation. We then identified the genes which had strongest coherence within clones. These genes significantly overlapped known B-cell fate determination programs, suggesting the genes which determine cell identity are most robustly controlled on a clonal level. Persistent clonal identities were also observed in human plasma cells from bone marrow, indicating that these transcriptional programs maintain long-term cell identities in vivo. Thus, we show how cell-intrinsic fate bias influences differentiation outcomes in vitro and in vivo.
Additional Information
© 2023 Swift et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). We thank Ivana Cvijovic, Elizabeth Jerison, Derek Croote, Bali Pulendran, Dan Jarosz, and Daria-Mochly Rosen for useful discussions and helpful comments on the manuscript. This work was supported by the National Science Foundation Graduate Research Fellowship Program (to M Swift).Attached Files
Published - LSA-2022-01792.pdf
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Additional details
- PMCID
- PMC9840405
- Eprint ID
- 119176
- Resolver ID
- CaltechAUTHORS:20230209-988069100.10
- NSF Graduate Research Fellowship
- Created
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2023-03-15Created from EPrint's datestamp field
- Updated
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2023-03-15Created from EPrint's last_modified field