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

YeEun Kim, Ariel A. Calderon, Patricia Favaro, David R. Glass, Albert G. Tsai, Daniel Ho, Luciene Borges, William J. Greenleaf () and Sean C. Bendall ()
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YeEun Kim: Stanford University
Ariel A. Calderon: Stanford University
Patricia Favaro: Stanford University
David R. Glass: 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

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-49883-w

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