Jaleco A C, Neves H, Hooijberg E, Gameiro P, Clode N, Haury M, Henrique D, Parreira L
Instituto de Histologia e Embriologia, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal.
J Exp Med. 2001 Oct 1;194(7):991-1002. doi: 10.1084/jem.194.7.991.
Notch signaling is known to differentially affect the development of lymphoid B and T cell lineages, but it remains unclear whether such effects are specifically dependent on distinct Notch ligands. Using a cell coculture assay we observed that the Notch ligand Delta-1 completely inhibits the differentiation of human hematopoietic progenitors into the B cell lineage while promoting the emergence of cells with a phenotype of T cell/natural killer (NK) precursors. In contrast, Jagged-1 did not disturb either B or T cell/NK development. Furthermore, cells cultured in the presence of either Delta-1 or Jagged-1 can acquire a phenotype of NK cells, and Delta-1, but not Jagged-1, permits the emergence of a de novo cell population coexpressing CD4 and CD8. Our results thus indicate that distinct Notch ligands can mediate differential effects of Notch signaling and provide a useful system to further address cell-fate decision processes in lymphopoiesis.
已知Notch信号通路对淋巴B细胞和T细胞谱系的发育有不同影响，但尚不清楚这些影响是否特别依赖于不同的Notch配体。通过细胞共培养试验，我们观察到Notch配体Delta-1完全抑制人类造血祖细胞向B细胞谱系的分化，同时促进具有T细胞/自然杀伤（NK）前体表型的细胞出现。相比之下，Jagged-1既不干扰B细胞发育，也不干扰T细胞/NK细胞发育。此外，在Delta-1或Jagged-1存在的情况下培养的细胞可以获得NK细胞表型，并且Delta-1而非Jagged-1能使共表达CD4和CD8的新生细胞群体出现。因此，我们的结果表明，不同的Notch配体可以介导Notch信号通路的不同效应，并提供了一个有用的系统来进一步研究淋巴细胞生成中的细胞命运决定过程。
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