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

Area of Science:

• Hematopoiesis
• Immunology
• Cell Biology

Background:

• Lymphoid cell specification from human hematopoietic progenitors remains incompletely understood.
• Linking lymphoid identity to specific protein markers in progenitor cells is crucial for advancing hematopoiesis research.

Purpose of the Study:

• To identify protein-level cell features associated with lymphoid identity in human bone marrow progenitors.
• To characterize novel progenitor populations that bridge the lympho-myeloid developmental axis.

Main Methods:

• Utilized highly multiplexed single-cell proteomic screening on human bone marrow progenitors.
• Performed chromatin accessibility assays to identify regulatory motifs.
• Conducted prospective isolation and ex vivo differentiation assays of identified progenitor subsets.

Main Results:

• Identified terminal deoxynucleotidyl transferase (TdT) expression in CD34+ progenitors preceding B/T cell emergence.
• Found TdT+ cells with a granulocyte-monocyte progenitor (GMP) immunophenotype but enriched lymphoid-associated transcription factor (TF) motifs.
• Demonstrated that CD84low GMPs exhibit robust lymphoid potential ex vivo while retaining myeloid capacity.

Conclusions:

• Identified a distinct population of human bone marrow lymphoid-primed progenitors.
• Characterized TdT as a novel marker for early lymphoid specification within GMPs.
• Defined a more nuanced understanding of the lympho-myeloid axis in human hematopoiesis.