Terminal deoxynucleotidyl transferase and CD84 identify human multi-potent lymphoid progenitors.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39003273.
- Also identified by DOI 10.1038/s41467-024-49883-w and PMC identifier 11246490.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>+</sup> progenitors prior to B/T cell emergence. While these TdT<sup>+</sup> 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 CD84<sup>lo</sup> 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.
Medical subject headings
- DNA Nucleotidylexotransferase
- Lymphoid Progenitor Cells