末端脱氧核苷酸转移酶和 CD84 可识别人类多能淋巴祖细胞。
Terminal deoxynucleotidyl transferase and CD84 identify human multi-potent lymphoid progenitors.
机构信息
Immunology Graduate Program, Stanford University, Stanford, CA, USA.
Department of Pathology, Stanford University, Stanford, CA, USA.
出版信息
Nat Commun. 2024 Jul 13;15(1):5910. doi: 10.1038/s41467-024-49883-w.
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 CD84 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.
人类造血祖细胞中的淋巴样特异性尚未完全阐明。为了更好地将淋巴样特征与蛋白质水平的细胞特征相关联，我们对人类骨髓祖细胞进行了高度多重化的单细胞蛋白质组学筛选。该筛选鉴定了末端脱氧核苷酸转移酶（TdT），一种内在的 VDJ 重组特异性 DNA 聚合酶，在 B/T 细胞出现之前广泛表达于 CD34 祖细胞中。虽然这些 TdT 细胞与粒细胞-单核细胞祖细胞（GMP）免疫表型一致，但它们可及染色质区域富含淋巴相关转录因子（TF）基序。GMP 上的 TdT 表达与 SLAM 家族成员 CD84 呈负相关。CD84 GMP 的前瞻性分离证明了体外强大的淋巴样潜能，同时仍然保留了显著的髓系分化能力，类似于 LMPP。这项多组学研究鉴定了人类骨髓淋巴样祖细胞，进一步定义了人类造血中的淋巴-髓样轴。
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