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Terminal deoxynucleotidyl transferase and CD84 identify human multi-potent lymphoid progenitors

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Listed:
  • YeEun Kim

    (Stanford University
    Stanford University)

  • Ariel A. Calderon

    (Stanford University
    Stanford University)

  • Patricia Favaro

    (Stanford University)

  • David R. Glass

    (Stanford University
    Stanford University)

  • Albert G. Tsai

    (Stanford University)

  • Daniel Ho

    (Stanford University)

  • Luciene Borges

    (Stanford University)

  • William J. Greenleaf

    (Stanford University)

  • Sean C. Bendall

    (Stanford University)

Abstract

Lymphoid specification in human hematopoietic progenitors is not fully understood. To better associate lymphoid identity with protein-level cell features, we conduct a highly multiplexed single-cell proteomic screen on human bone marrow progenitors. This screen identifies terminal deoxynucleotidyl transferase (TdT), a specialized DNA polymerase intrinsic to VDJ recombination, broadly expressed within CD34+ progenitors prior to B/T cell emergence. While these TdT+ cells coincide with granulocyte-monocyte progenitor (GMP) immunophenotype, their accessible chromatin regions show enrichment for lymphoid-associated transcription factor (TF) motifs. TdT expression on GMPs is inversely related to the SLAM family member CD84. Prospective isolation of CD84lo GMPs demonstrates robust lymphoid potentials ex vivo, while still retaining significant myeloid differentiation capacity, akin to LMPPs. This multi-omic study identifies human bone marrow lymphoid-primed progenitors, further defining the lympho-myeloid axis in human hematopoiesis.

Suggested Citation

  • YeEun Kim & Ariel A. Calderon & Patricia Favaro & David R. Glass & Albert G. Tsai & Daniel Ho & Luciene Borges & William J. Greenleaf & Sean C. Bendall, 2024. "Terminal deoxynucleotidyl transferase and CD84 identify human multi-potent lymphoid progenitors," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49883-w
    DOI: 10.1038/s41467-024-49883-w
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