A developmental switch in thymic lymphocyte maturation potential occurs at the level of hematopoietic stem cells

Ikuta, Koichi; Kina, Tatsuo; MacNeil, Ian A.; Uchida, Naoshige; Péault, Bruno; Chien, Yueh‐hsiu; Weissman, Irving L.

doi:10.1016/0092-8674(90)90262-d

Cited by 567 publications

(372 citation statements)

References 35 publications

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“…They enter the heart at the stage of development corresponding to the established erythroid lineage, not at the stage of hematopoietic progenitor cells. This was confirmed by their more mature morphology (ultrastructure) as compared to the erythroblasts of yolk sac blood islands (Haar and Ackerman 1971;Tavassoli, 1991) and their Ter/119 antigen expression, the latter being specific to cells of erythroid/erythrocyte stage (Ikuta et al, 1990). A similar observation, namely, that commitment to hematopoietic lineage precedes the formation of blood island-like structures in the embryonic heart, has been suggested in a previous study by Kattan et al (2004).…”

Section: Discussionsupporting

confidence: 75%

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Vasculogenesis of the embryonic heart: Origin of blood island‐like structures

et al. 2006

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The earliest vascular structures (blood island-like) in the embryonic heart are clusters of angioblasts and nucleated red blood cells (NRBCs), which differentiate into endothelial cells and erythrocytes, respectively. Our purpose was to define the area and chronology of NRBC appearance in the mouse embryonic heart at the stages before a patency between coronary vessels and peripheral circulation is established (10.5-13.5 dpc). Before and at the onset of vascularization, NBCs were not present within the proepicardium; however, Ter/119 ϩ differentiating erythroblasts and single scattered CD45 ϩ were found in the heart beginning from 10.5 dpc. The Ter/119 ϩ cells were in close apposition to angioblasts (PECAM1 ϩ ) and were recognized as components of blood island-like structures or vascular vesicles in transmission electron microscope and were located mostly in the subepicardium. Some of the NRBCs were not accompanied by angioblasts and located close to the endocardial endothelium or at the border of the endocardial endothelium or in the subepicardium. These erythroblasts were beginning to assemble with angioblasts. CD34 ϩ NBCs as well as progenitor cells of erythroid lineage were not detected in the heart at these stages of development. The state of differentiation of NRBCs of blood islands was similar/the same as the morphology of circulating blood cells at the respective stages of embryo development. The presence of mature NRBCs in the subendocardial area and lack of progenitor cells of erythroid lineage within the heart indicate that erythroid commitment occurs outside the heart. We suggest that NRBCs enter the heart from the blood stream at 10.5-12 dpc independently from angioblasts.

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Section: Discussionsupporting

confidence: 75%

“…Some individual cells of erythroblastic lineage (which exhibit Ter/119 antigen) (Ikuta et al, 1990) were found to be located on the border of the endocardial endothelium (Figs. 5d, 6), as if pictured while moving across the endocardial endothelium.…”

Section: Discussionmentioning

confidence: 99%

Vasculogenesis of the embryonic heart: Origin of blood island‐like structures

et al. 2006

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“…Several reports have demonstrated that normal TCR␥␦ ϩ DETCs are exclusively derived from fetal thymocyte precursors (10,40,44). In this study, the junctional sequences of TCR ␥-and ␦-chains in DETCs from V␦1 Ϫ/Ϫ mice strongly suggested that V␥5 ϩ DETCs as well as V␥5 Ϫ DETCs were derived from fetal and/or newborn thymocytes rather than adult sources (Fig.…”

Section: Discussionmentioning

confidence: 62%

Development of Dendritic Epidermal T Cells with a Skewed Diversity of γδTCRs in Vδ1-Deficient Mice

Hara¹,

Kishihara²,

Matsuzaki³

et al. 2000

The Journal of Immunology

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One of the most intriguing features of γδ T cells that reside in murine epithelia is the association of a specific Vγ/Vδ usage with each epithelial tissue. Dendritic epidermal T cells (DETCs) in the murine epidermis, are predominantly derived from the “first wave” Vγ5+ fetal thymocytes and overwhelmingly express the canonical Vγ5/Vδ1-TCRs lacking junctional diversity. Targeted disruption of the Vδ1 gene resulted in a markedly impaired development of Vγ5+ fetal thymocytes as precursors of DETCs; however, γδTCR+ DETCs with a typical dendritic morphology were observed in Vδ1−/− mice and their cell densities in the epidermis were slightly lower than those in Vδ1+/− epidermis. Moreover, the Vδ1-deficient DETCs were functionally competent in their ability to up-regulate cytokines and keratinocyte growth factor-expression in response to keratinocytes. Vγ5+ DETCs were predominant in the Vδ1−/− epidermis, though Vγ5− γδTCR+ DETCs were also detected. The Vγ5+ DETCs showed a typical dendritic shape, γδTCRhigh, and age-associated expansion in epidermis as observed in conventional DETCs of normal mice, whereas the Vγ5− γδTCR+ DETCs showed a less dendritic shape, γδTCRlow, and no expansion in the epidermis, consistent with their immaturity. These results suggest that optimal DETC development does not require a particular Vγ/Vδ-chain usage but requires expression of a limited diversity of γδTCRs, which allow DETC precursors to mature and expand within the epidermal microenvironment.

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“…The di erentiation could also be demonstrated by the increase in the level of b-globin mRNA and in the extent of staining with erythroid cell-speci®c monoclonal antibody, TER-119 (Ikuta et al, 1990;Aisaki et al, 1999) (Figure 3). …”

Section: Effects Of Ras Mutants On Erythroid Differentiation Of Skt6 mentioning

confidence: 91%

Induction of erythroid differentiation by inhibition of Ras/ERK pathway in a Friend murine leukemia cell line

et al. 2000

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The role of Ras and MAP kinases (MAPKs) in the regulation of erythroid di erentiation was studied using a cell line (SKT6) derived from Friend virus (Anemic strain)-induced murine erythroleukemia. This cell line undergoes di erentiation in vitro in response to erythropoietin (EPO) or other chemical inducers such as dimethylsulfoxide (DMSO). When a constitutively active ras mutant (ras12V) was expressed in SKT6 cells, EPO-induced di erentiation was inhibited. Conversely, a dominant negative ras mutant (ras17N) induced di erentiation even in the absence of EPO, suggesting that the basal Ras activity is essential for the maintenance of the undi erentiated phenotype and proliferative potential in this cell line. Rapid inactivation of ERK was observed after expression of ras17N. Slow but signi®cant inactivation of ERK was also observed during EPOinduced di erentiation. Furthermore, overexpression of a constitutively active mutant of ERK-activating kinase (MAPKK) was found to suppress erythroid di erentiation, while pharmacological inhibition of MAPKK induced di erentiation. These ®ndings suggest that down-regulation of Ras/ERK signaling pathway may be an essential event in EPO-induced erythroid di erentiation in this system. Oncogene (2000) 19, 1500 ± 1508.

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A developmental switch in thymic lymphocyte maturation potential occurs at the level of hematopoietic stem cells

Cited by 567 publications

References 35 publications

Vasculogenesis of the embryonic heart: Origin of blood island‐like structures

Vasculogenesis of the embryonic heart: Origin of blood island‐like structures

Development of Dendritic Epidermal T Cells with a Skewed Diversity of γδTCRs in Vδ1-Deficient Mice

Induction of erythroid differentiation by inhibition of Ras/ERK pathway in a Friend murine leukemia cell line

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