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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, Vol. 212, No. 10, 21.09.2015, p. 1589-601.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Ziętara, N, Łyszkiewicz, M, Puchałka, J, Witzlau, K, Reinhardt, A, Förster, R, Pabst, O, Prinz, I & Krueger, A 2015, 'Multicongenic fate mapping quantification of dynamics of thymus colonization', J EXP MED, vol. 212, no. 10, pp. 1589-601. https://doi.org/10.1084/jem.20142143

APA

Ziętara, N., Łyszkiewicz, M., Puchałka, J., Witzlau, K., Reinhardt, A., Förster, R., Pabst, O., Prinz, I., & Krueger, A. (2015). Multicongenic fate mapping quantification of dynamics of thymus colonization. J EXP MED, 212(10), 1589-601. https://doi.org/10.1084/jem.20142143

Vancouver

Ziętara N, Łyszkiewicz M, Puchałka J, Witzlau K, Reinhardt A, Förster R et al. Multicongenic fate mapping quantification of dynamics of thymus colonization. J EXP MED. 2015 Sep 21;212(10):1589-601. https://doi.org/10.1084/jem.20142143

Bibtex

@article{482671d607134b988464019157d8f630,
title = "Multicongenic fate mapping quantification of dynamics of thymus colonization",
abstract = "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. ",
keywords = "Animals, Cell Lineage, Mice, Inbred C57BL, Mice, Knockout, Receptors, CCR/genetics, Receptors, CCR7/genetics, Receptors, Interleukin-17/genetics, Stem Cells/physiology, T-Lymphocytes/cytology, Thymocytes/physiology, Thymus Gland/cytology",
author = "Natalia Zi{\c e}tara and Marcin {\L}yszkiewicz and Jacek Pucha{\l}ka and Katrin Witzlau and Annika Reinhardt and Reinhold F{\"o}rster and Oliver Pabst and Immo Prinz and Andreas Krueger",
note = "{\textcopyright} 2015 Zi{\c e}tara et al.",
year = "2015",
month = sep,
day = "21",
doi = "10.1084/jem.20142143",
language = "English",
volume = "212",
pages = "1589--601",
journal = "J EXP MED",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "10",

}

RIS

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 -