Luis Tiago C, Luc Sidinh, Mizukami Takuo, Boukarabila Hanane, Thongjuea Supat, Woll Petter S, Azzoni Emanuele, Giustacchini Alice, Lutteropp Michael, Bouriez-Jones Tiphaine, Vaidya Harsh, Mead Adam J, Atkinson Deborah, Böiers Charlotta, Carrelha Joana, Macaulay Iain C, Patient Roger, Geissmann Frederic, Nerlov Claus, Sandberg Rickard, de Bruijn Marella F T R, Blackburn C Clare, Godin Isabelle, Jacobsen Sten Eirik W
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom.
Hematopoietic Stem Cell Laboratory, Lund Stem Cell Center, Lund University, Klinikgatan 26, 221 84, Lund, Sweden.
Nat Immunol. 2016 Dec;17(12):1424-1435. doi: 10.1038/ni.3576. Epub 2016 Oct 3.
The final stages of restriction to the T cell lineage occur in the thymus after the entry of thymus-seeding progenitors (TSPs). The identity and lineage potential of TSPs remains unclear. Because the first embryonic TSPs enter a non-vascularized thymic rudiment, we were able to directly image and establish the functional and molecular properties of embryonic thymopoiesis-initiating progenitors (T-IPs) before their entry into the thymus and activation of Notch signaling. T-IPs did not include multipotent stem cells or molecular evidence of T cell-restricted progenitors. Instead, single-cell molecular and functional analysis demonstrated that most fetal T-IPs expressed genes of and had the potential to develop into lymphoid as well as myeloid components of the immune system. Moreover, studies of embryos deficient in the transcriptional regulator RBPJ demonstrated that canonical Notch signaling was not involved in pre-thymic restriction to the T cell lineage or the migration of T-IPs.
在胸腺播种祖细胞（TSPs）进入胸腺后，T细胞谱系限制的最后阶段在胸腺中发生。TSPs的身份和谱系潜能仍不清楚。由于第一批胚胎TSPs进入未血管化的胸腺原基，我们能够在胚胎胸腺生成起始祖细胞（T-IPs）进入胸腺并激活Notch信号之前，直接成像并确定其功能和分子特性。T-IPs不包括多能干细胞或T细胞限制性祖细胞的分子证据。相反，单细胞分子和功能分析表明，大多数胎儿T-IPs表达免疫系统淋巴样和髓样成分的基因，并有可能发育成这些成分。此外，对转录调节因子RBPJ缺陷胚胎的研究表明，经典Notch信号不参与胸腺前T细胞谱系限制或T-IPs的迁移。
