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This manuscript describes the kinetics of fate decisions within the thymus following intravenous injection of adult BM-derived HSCs. It takes ~13 days for arriving cells to become DP cells. During the first 10 days, the cells remain at the DN1 stage near the corticomedullary junction where they arrived. Development to the DN2 stage is asynchronous and is associated with movement from this region into the deeper cortex. Further differentiation to the DN3 stage is accompanied by movement across the midpoint of the cortex. Interestingly, the first lineage-positive cells that can be identified within the thymus are dendritic cells in the medulla, suggesting that the arrival of thymocytes is preceded by cells that modulate their activity.
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Porritt H.E., Gordon K., Petrie H.T. Kinetics of steady-state differentiation and mapping of intrathymic-signaling environments by stem cell transplantation in nonirradiated mice. J Exp Med. 198:2003;957-962 This manuscript describes the kinetics of fate decisions within the thymus following intravenous injection of adult BM-derived HSCs. It takes ~13 days for arriving cells to become DP cells. During the first 10 days, the cells remain at the DN1 stage near the corticomedullary junction where they arrived. Development to the DN2 stage is asynchronous and is associated with movement from this region into the deeper cortex. Further differentiation to the DN3 stage is accompanied by movement across the midpoint of the cortex. Interestingly, the first lineage-positive cells that can be identified within the thymus are dendritic cells in the medulla, suggesting that the arrival of thymocytes is preceded by cells that modulate their activity.
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+ population (termed CLP-2) that appear to selectively colonize the thymus and are capable of T cell, B cell, NK cell and DC development. Their lineage studies place the CLP-2 population directly downstream from BM CLPs. Although this BM population is capable of T-cell production, several factors discussed in the text suggest that this population is not the physiological early T-cell progenitor.
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+ population (termed CLP-2) that appear to selectively colonize the thymus and are capable of T cell, B cell, NK cell and DC development. Their lineage studies place the CLP-2 population directly downstream from BM CLPs. Although this BM population is capable of T-cell production, several factors discussed in the text suggest that this population is not the physiological early T-cell progenitor.
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neg/low and contains all of the T-cell progenitor activity within the DN1 fraction. This population differs in several important aspects from BM-derived CLPs. They are non-responsive to IL-7, more efficient at T-cell development, less efficient at B-cell development, and retained some capacity to generate myeloid cells. Of particular significance, ETPs, but not CLPs, can be found in Ikaros-deficient mice, which are able to generate T cells but not B cells. All of these characteristics suggest that this population is likely to contain the physiological progenitors of T cells.
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neg/low and contains all of the T-cell progenitor activity within the DN1 fraction. This population differs in several important aspects from BM-derived CLPs. They are non-responsive to IL-7, more efficient at T-cell development, less efficient at B-cell development, and retained some capacity to generate myeloid cells. Of particular significance, ETPs, but not CLPs, can be found in Ikaros-deficient mice, which are able to generate T cells but not B cells. All of these characteristics suggest that this population is likely to contain the physiological progenitors of T cells.
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••] to investigate fetal lymphoid development. Cells expressing low/intermediate levels of GFP also express Mac-1 (and Thy1.2 to a lesser extent). This suggests that care must be used in cell purification as these antigens are used to delete lineage-committed cells. This manuscript and others (e.g. [28]) suggest that murine fetal lymphoid development is different than adult lymphoid development.
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•] demonstrate that Rel/NF-κB family members play important roles in NKT-cell development. Most intriguing is the identification that RelB is required in the thymic stroma, possibly for regulation of IL-15 production.
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•] demonstrate that Rel/NF-κB family members play important roles in NKT-cell development. Most intriguing is the identification that RelB is required in the thymic stroma, possibly for regulation of IL-15 production.
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