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Cited by 40T-cell and B-cell ImmunologyHematopoietic Stem Cell TransplantationDevelopmental Biology and Gene Regulation

Multicongenic fate mapping quantification of dynamics of thymus colonization

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Ziętara, Natalia, Łyszkiewicz, Marcin, Puchałka, Jacek, Witzlau, Katrin, Reinhardt, Annika, Förster, Reinhold, Pabst, Oliver, Prinz, Immo +1 more·2015·Journal of Experimental Medicine
DOI 10.1084/jem.20142143PMC PMC4577840
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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.

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  • Cells in these stages are hard to visualize in the intact thymus, as only a few cells per day enter the thymic antechamber, then migrate slowly through the cortex, dispersing among more advanced T-cell precursors.

    “However, cells in these stages are hard to visualize in the intact thymus, as only a few cells per day are granted regulated entry into the thymic antechamber (127), then migrate slowly through the cortex, dispersing among a vast excess of more advanced T-cell precursors, as they begin to differentiate toward commitment (128).”

    From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [127]

    The Abstract (page unavailable) says that low numbers of progenitors enter the thymus, making them difficult to characterize, and describes thymus colonization as tightly controlled. Its estimate of 10–200 cells per day, however, is explicitly for irradiated adult thymi; it does not establish that daily rate for the intact, unirradiated thymus. The later migration through the cortex is attached to citation (128), not this source. (LLM, conf=0.84)

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Cited by

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Authors
Ziętara, N., Łyszkiewicz, M., Puchałka, J., Witzlau, K., Reinhardt, A., Förster, R., Pabst, O., Prinz, I., & Krueger, A.
Affiliations
  • Medizinische Hochschule Hannover (DE)
  • Ludwig-Maximilians-Universität München (DE)
Corresponding author
  • Ziętara, Natalia
  • Krueger, Andreas
ORCID
Venue
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2015-09-07
Volume
212
Issue
10
Pages
1589-1601
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20142143
PMC
PMC4577840
OpenAlex
W1913095327
Cited by
40
References
2
Citations by year
2026: 2 · 2025: 5 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 8 · 2016: 6
FWCI
2.79
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • RWTH Publications (RWTH Aachen) (submittedVersion, other-oa)
  • RWTH Publications (RWTH Aachen)
Funders
  • Deutsche Forschungsgemeinschaft (SFB738‐A7, SFB-738, Exc-62, KR2320/3-1)
  • Medizinischen Hochschule Hannover (EXC62, SFB738)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
thymus colonization, T cell development, CCR7, CCR9, serial transfer, preconditioning
MeSH terms
Animals, Mice, Inbred C57BL, Stem Cells, T-Lymphocytes, Thymus Gland, Mice, Knockout, Cell Lineage, Receptors, Interleukin-17, Receptors, CCR, Receptors, CCR7, Thymocytes

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