Multicongenic fate mapping quantification of dynamics of thymus colonization
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Multicongenic fate mapping quantification of dynamics of thymus colonization. / Ziętara, Natalia; Łyszkiewicz, Marcin; Puchałka, Jacek; Witzlau, Katrin; Reinhardt, Annika; Förster, Reinhold; Pabst, Oliver; Prinz, Immo; Krueger, Andreas.
in: J EXP MED, Jahrgang 212, Nr. 10, 21.09.2015, S. 1589-601.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Multicongenic fate mapping quantification of dynamics of thymus colonization
AU - Ziętara, Natalia
AU - Łyszkiewicz, Marcin
AU - Puchałka, Jacek
AU - Witzlau, Katrin
AU - Reinhardt, Annika
AU - Förster, Reinhold
AU - Pabst, Oliver
AU - Prinz, Immo
AU - Krueger, Andreas
N1 - © 2015 Ziętara et al.
PY - 2015/9/21
Y1 - 2015/9/21
N2 - Postnatal T cell development depends on continuous colonization of the thymus by BM-derived T lineage progenitors. Both quantitative parameters and the mechanisms of thymus seeding remain poorly understood. Here, we determined the number of dedicated thymus-seeding progenitor niches (TSPNs) capable of supporting productive T cell development, turnover rates of niche occupancy, and feedback mechanisms. To this end, we established multicongenic fate mapping combined with mathematical modeling to quantitate individual events of thymus colonization. We applied this method to study thymus colonization in CCR7(-/-)CCR9(-/-) (DKO) mice, whose TSPNs are largely unoccupied. We showed that ∼160-200 TSPNs are present in the adult thymus and, on average, 10 of these TSPNs were open for recolonization at steady state. Preconditioning of wild-type mice revealed a similar number of TSPNs, indicating that preconditioning can generate space efficiently for transplanted T cell progenitors. To identify potential cellular feedback loops restricting thymus colonization, we performed serial transfer experiments. These experiments indicated that thymus seeding was directly restricted by the duration of niche occupancy rather than long-range effects, thus challenging current paradigms of thymus colonization.
AB - Postnatal T cell development depends on continuous colonization of the thymus by BM-derived T lineage progenitors. Both quantitative parameters and the mechanisms of thymus seeding remain poorly understood. Here, we determined the number of dedicated thymus-seeding progenitor niches (TSPNs) capable of supporting productive T cell development, turnover rates of niche occupancy, and feedback mechanisms. To this end, we established multicongenic fate mapping combined with mathematical modeling to quantitate individual events of thymus colonization. We applied this method to study thymus colonization in CCR7(-/-)CCR9(-/-) (DKO) mice, whose TSPNs are largely unoccupied. We showed that ∼160-200 TSPNs are present in the adult thymus and, on average, 10 of these TSPNs were open for recolonization at steady state. Preconditioning of wild-type mice revealed a similar number of TSPNs, indicating that preconditioning can generate space efficiently for transplanted T cell progenitors. To identify potential cellular feedback loops restricting thymus colonization, we performed serial transfer experiments. These experiments indicated that thymus seeding was directly restricted by the duration of niche occupancy rather than long-range effects, thus challenging current paradigms of thymus colonization.
KW - Animals
KW - Cell Lineage
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Receptors, CCR/genetics
KW - Receptors, CCR7/genetics
KW - Receptors, Interleukin-17/genetics
KW - Stem Cells/physiology
KW - T-Lymphocytes/cytology
KW - Thymocytes/physiology
KW - Thymus Gland/cytology
U2 - 10.1084/jem.20142143
DO - 10.1084/jem.20142143
M3 - SCORING: Journal article
C2 - 26347471
VL - 212
SP - 1589
EP - 1601
JO - J EXP MED
JF - J EXP MED
SN - 0022-1007
IS - 10
ER -