Two waves of distinct hematopoietic progenitor cells colonize the fetal thymus

Ramond, Cyrille; Berthault, Claire; Burlen-Defranoux, Odile; Sousa, Ana Pereira de; Guy‐Grand, Delphine; Vieira, Paulo; Pereira, Pablo; Cumano, Ana

doi:10.1038/ni.2782

Cited by 91 publications

(116 citation statements)

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“…Recently, it has been shown that the second wave-progenitors colonizing thymus just before birth retain robust B cell potential in addition to myeloid potential (Luc et al 2012;Ramond et al 2014). It is therefore probable that the second wave-progenitors are close to MLPs.…”

Section: Prethymic Pathway Of T Cell Developmentmentioning

confidence: 97%

Generation and Regeneration of T Cells

Kawamoto

Ikawa

Maeda

et al. 2016

Synthetic Immunology

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T cells contain a variety of lineages, each of which is formed by passing through a number of strictly regulated steps. In this article we aim to clarify essential factors and critical developmental steps during T cell development. First, we will describe the process of T cell development that occurs in vivo. Then, by presenting recent approaches in synthetic biology, we will show that, in the murine case, a feeder-free culture system using a combination of cytokines and Notch ligand is sufficient to support T cell development starting from multipotent hematopoietic progenitors to the TCR-expressing CD4 + CD8+ stage. Finally, in the human case, we will show that mature functional CD8 + killer T cells can be produced in vitro starting as early as from the ES/iPS cell stage using feeder cells. These studies may help clarify "minimal requirements" for T cell development.

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Section: Prethymic Pathway Of T Cell Developmentmentioning

confidence: 97%

Generation and Regeneration of T Cells

Kawamoto

Ikawa

Maeda

et al. 2016

Synthetic Immunology

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“…*p , 0.05. cortical thymic epithelial cell differentiation can be regulated in a LTbR-dependent fashion (45). Furthermore, hematopoietic progenitors that seed the thymus comprise a relatively heterogeneous mixture of cells, including common lymphocyte progenitors and early thymic progenitors, which all express IL-7Ra (26,40). This being said, we are unable to experimentally exclude a potential role for more mature lymphoid lineages in the thymus with a history of IL-7Ra expression, although the absence of a NKT1 a subset phenotype in CD4-cre;LTb F/F , CD79a-cre;LTb F/F , and CD11c-cre;LTb F/F mice (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Three, potential cellular lineage(s)-expressing LTb should presumably have a nonredundant role during thymic organogenesis. Based on these criteria, we postulated that hematopoietic and/or lymphoid precursors to the T lymphocyte lineage may be viable candidates as they can be detected within the thymic anlage from E11.5 onward (39,40) and are reported to promote differentiation of thymic stromal tissue (12,41). Thus, to assess the role of hematopoietic and/or lymphoid progenitors as a cellular source for LTb during NKT1 a development , we selected a mouse line expressing cre-recombinase under the control of the IL-7Ra promoter (26).…”

Section: Lymph Node Aplasia In Germline Ltb-deficient Mice Does Not Imentioning

confidence: 99%

The Thymic Microenvironment Differentially Regulates Development and Trafficking of Invariant NKT Cell Sublineages

Drennan

Govindarajan

Wilde

et al. 2014

The Journal of Immunology

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The regulatory role of the thymic microenvironment during trafficking and differentiation of the invariant NKT (iNKT) cell lineage remains poorly understood. In this study, we show that fractalkine receptor expression marks emigrating subpopulations of the NKT1, NKT2, and NKT17 sublineages in the thymus and peripheral organs of naive mice. Moreover, NKT1 sublineage cells can be subdivided into two subsets, namely NKT1a and NKT1b, which exhibit distinct developmental and tissue-specific distribution profiles. More specifically, development and trafficking of the NKT1a subset are selectively dependent upon lymphotoxin (LT)α1β2-LTβ receptor–dependent differentiation of thymic stroma, whereas the NKT1b, NKT2, and NKT17 sublineages are not. Furthermore, we identify a potential cellular source for LTα1β2 during thymic organogenesis, marked by expression of IL-7Rα, which promotes differentiation of the NKT1a subset in a noncell-autonomous manner. Collectively, we propose a mechanism by which thymic differentiation and retention of the NKT1 sublineage are developmentally coupled to LTα1β2-LTβ receptor–dependent thymic organogenesis.

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“…The fact that T cells can be generated from fetal HPC does not in itself prove the presence of multipotent progenitors or HSC, since it has been shown that T cells can be generated from YS precursors that arise before HSC are generated. 19,20 Selfrenewal of HSC is evaluated by their ability to reconstitute immune deficient mice. Previous studies have reported re-population by in vitro hESC-derived HPC.…”

Section: Discussionmentioning

confidence: 99%