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

被引:0
作者
Kim, YeEun [1 ,2 ]
Calderon, Ariel A. [1 ,2 ]
Favaro, Patricia [2 ]
Glass, David R. [1 ,2 ]
Tsai, Albert G. [2 ]
Ho, Daniel [2 ]
Borges, Luciene [2 ]
Greenleaf, William J. [3 ]
Bendall, Sean C. [2 ]
机构
[1] Stanford Univ, Immunol Grad Program, Stanford, CA USA
[2] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA
[3] Stanford Univ, Dept Genet, Stanford, CA 94305 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
HEMATOPOIETIC STEM; LINEAGE COMMITMENT; DENDRITIC CELLS; BONE-MARROW; B-CELL; MASS CYTOMETRY; EXPRESSION; SPECIFICATION; IMMUNE; DIFFERENTIATION;
D O I
10.1038/s41467-024-49883-w
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. How lymphoid and myeloid specification occurs in human haematopoietic progenitors is not fully understood. Here the authors perform a proteomic screen on human bone marrow progenitors and suggest TdT+ and CD84- progenitors as lymphoid-primed progenitors with residual myeloid potentials.
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页数:15
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