Multicongenic fate mapping quantification of dynamics of thymus colonization

The Journal of Experimental Medicine
Natalia ZiętaraAndreas Krueger

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, ...Continue Reading

References

May 1, 1976·The Journal of Experimental Medicine·J L Kadish, R S Basch
Jan 1, 1975·Transplantation·V J WallisA J Davies
May 5, 1997·FEBS Letters·M OkabeY Nishimune
Feb 7, 2001·The Journal of Experimental Medicine·D L FossI Goldschneider
Sep 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elina DonskoyIrving Goldschneider
Oct 25, 2003·Clinical & Developmental Immunology·Ana Paula LepiqueHoward T Petrie
Mar 3, 2004·Nature Immunology·Tamar E BoursalianPamela J Fink
Jul 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Susan E Prockop, Howard T Petrie
Aug 11, 2004·The Journal of Experimental Medicine·Tomoo UenoYousuke Takahama
Aug 11, 2004·The Journal of Experimental Medicine·Ana MisslitzReinhold Förster
May 10, 2005·Nature Immunology·Fabio M V RossiHermann J Ziltener
Apr 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·M Lucila ScimoneUlrich H von Andrian
Jul 19, 2006·The Journal of Experimental Medicine·Andreas KruegerHarald von Boehmer
Jan 16, 2007·Immunity·Andreas Krueger, Harald von Boehmer
Feb 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Benjamin A SchwarzAvinash Bhandoola
Feb 13, 2007·Annual Review of Immunology·Howard T Petrie, Juan Carlos Zúñiga-Pflücker
Feb 27, 2008·The Journal of Experimental Medicine·Linda KeninsAleksandra Wodnar-Filipowicz
Apr 11, 2008·Nature·J Jeremiah Bell, Avinash Bhandoola
Apr 11, 2008·Nature·Haruka WadaHiroshi Kawamoto
Mar 18, 2009·The Journal of Experimental Medicine·Klaus GossensHermann J Ziltener
Dec 8, 2009·Blood·Daniel A ZlotoffAvinash Bhandoola
Mar 23, 2010·Immunity·Susan M SchlennerHans-Reimer Rodewald
Jul 17, 2010·Trends in Immunology·Susan M Schlenner, Hans-Reimer Rodewald
Dec 18, 2010·Blood·Lauren I Richie EhrlichIrving L Weissman
Feb 22, 2012·Nature Immunology·Sidinh LucSten Eirik W Jacobsen
Jul 11, 2012·The Journal of Experimental Medicine·Laetitia PeaudecerfBenedita Rocha
Jul 11, 2012·The Journal of Experimental Medicine·Vera C MartinsHans-Reimer Rodewald
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Oct 13, 2012·Nature Protocols·Ali ErtürkHans-Ulrich Dodt
Mar 16, 2013·Science·Veit R BuchholzDirk H Busch
Jul 31, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lisa FöhseImmo Prinz
May 16, 2014·Nature·Vera C MartinsHans-Reimer Rodewald

❮ Previous
Next ❯

Citations

Nov 16, 2016·Trends in Immunology·Andreas KruegerMarcin Łyszkiewicz
Apr 8, 2017·European Journal of Immunology·Ciro N R LinoImmo Prinz
Dec 31, 2017·Archivum Immunologiae Et Therapiae Experimentalis·Andreas Krueger
Jul 19, 2017·Cold Spring Harbor Perspectives in Biology·Hiroyuki Hosokawa, Ellen V Rothenberg
Sep 7, 2018·The FEBS Journal·Rafael A PaivaVera C Martins
Aug 24, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Beth LucasGraham Anderson
Jul 6, 2018·Cellular & Molecular Immunology·Georgios L MoschovakisReinhold Förster
May 4, 2017·Immunological Reviews·Stephen R DaleyDaniel H D Gray
Aug 23, 2017·Scientific Reports·Georgios L MoschovakisReinhold Förster
May 1, 2021·Entropy·Philippe A RobertAndreas Krueger

❮ Previous
Next ❯

Methods Mentioned

BETA
fluorescence microscopy
FACS
PCR
flow cytometry

Software Mentioned

ImageJ
GraphPad Prism
CellSens
LSFM
FlowJo
Imaris
R

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.