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Lineage tracing reveals fate bias and transcriptional memory in human B cells

Swift, Michael and Horns, Felix and Quake, Stephen R. (2023) Lineage tracing reveals fate bias and transcriptional memory in human B cells. Life Science Alliance, 6 (3). Art. No. e202201792. ISSN 2575-1077. PMCID PMC9840405. doi:10.26508/lsa.202201792.

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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.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Swift, Michael0000-0001-6391-0050
Horns, Felix0000-0001-5872-5061
Quake, Stephen R.0000-0002-1613-0809
Additional Information:© 2023 Swift et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at 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).
Funding AgencyGrant Number
NSF Graduate Research FellowshipUNSPECIFIED
Issue or Number:3
PubMed Central ID:PMC9840405
Record Number:CaltechAUTHORS:20230209-988069100.10
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:119176
Deposited By: Research Services Depository
Deposited On:15 Mar 2023 23:31
Last Modified:15 Mar 2023 23:31

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