CoChat
Sign Up
Cited by 79T-cell and B-cell ImmunologyHematopoietic Stem Cell TransplantationDevelopmental Biology and Gene Regulation

A dynamic niche provides Kit ligand in a stage-specific manner to the earliest thymocyte progenitors

Open access
Buono, Mario, Facchini, Raffaella, Matsuoka, Sahoko, Thongjuea, Supat, Waithe, Dominique, Luis, Tiago C., Giustacchini, Alice, Besmer, Peter +3 more·2016·Nature Cell Biology
DOI 10.1038/ncb3299PMC PMC4972409
Open this paper in CoChat — free account

Abstract

Thymic T cell development is initiated from bone-marrow-derived multi potent thymus-seeding progenitors. During the early stages of thymocyte differentiation, progenitors become T cell restricted. However, the cellular environments supporting these critical initial stages of T cell development within the thymic cortex are not known. Here we use the dependence of early, c-Kit-expressing thymic progenitors on Kit ligand (KitL) to show that CD4(-)CD8(-)c-Kit(+)CD25(-) DN1-stage progenitors associate with, and depend on, the membrane-bound form of KitL (mKitL) provided by a cortex-specific KitL-expressing vascular endothelial cell (VEC) population. In contrast, the subsequent CD4(-)CD8(-)c-Kit(+)CD25(+) DN2-stage progenitors associate selectively with cortical thymic epithelial cells (cTECs) and depend on cTEC-presented mKitL. These results show that the dynamic process of early thymic progenitor differentiation is paralleled by migration-dependent change to the supporting niche, and identify VECs as a thymic niche cell, with mKitL as a critical ligand.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/ncb3299

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 43

  1. [1]Scadden DT Nice neighborhood: emerging concepts of the stem cell niche Cell 2014 157 41 50 24679525 PMC4161226
  2. [2]Scadden DT The stem-cell niche as an entity of action Nature 2006 441 1075 1079 16810242
  3. [4]Zhu J Osteoblasts support B-lymphocyte commitment and differentiation from hematopoietic stem cells Blood 2007 109 3706 3712 17227831
  4. [5]Ding L Morrison SJ Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches Nature 2013 495 231 235 23434755 PMC3600153
  5. [6]Bunting MD Comerford I McColl SR Finding their niche: chemokines directing cell migration in the thymus Immunol Cell Biol 2011 89 185 196 21135866
  6. [7]Love PE Bhandoola A Signal integration and crosstalk during thymocyte migration and emigration Nat Rev Immunol 2011 11 469 477 21701522 PMC3710714
  7. [8]Radtke F Deficient T cell fate specification in mice with an induced inactivation of Notch1 Immunity 1999 10 547 558 10367900
  8. [9]Koch U Delta-like 4 is the essential, nonredundant ligand for Notch1 during thymic T cell lineage commitment J Exp Med 2008 205 2515 2523 18824585 PMC2571927
  9. [10]von Freeden-Jeffry U Solvason N Howard M Murray R The earliest T lineage-committed cells depend on IL-7 for Bcl-2 expression and normal cell cycle progression Immunity 1997 7 147 154 9252127
  10. [11]Sitnicka E Critical role of FLT3 ligand in IL-7 receptor independent T lymphopoiesis and regulation of lymphoid-primed multipotent progenitors Blood 2007 110 2955 2964 17540845
  11. [12]Kwan J Killeen N CCR7 directs the migration of thymocytes into the thymic medulla J Immunol 2004 172 3999 4007 15034011
  12. [13]Trampont PC CXCR4 acts as a costimulator during thymic beta-selection Nat Immunol 2010 11 162 170 20010845 PMC2808461
  13. [14]Shah DK Zuniga-Pflucker JC An overview of the intrathymic intricacies of T cell development J Immunol 2014 192 4017 4023 24748636
  14. [15]Tsai PT Lee RA Wu H BMP4 acts upstream of FGF in modulating thymic stroma and regulating thymopoiesis Blood 2003 102 3947 3953 12920023
  15. [16]Heinonen KM Wnt4 regulates thymic cellularity through the expansion of thymic epithelial cells and early thymic progenitors Blood 2011 118 5163 5173 21937690
  16. [17]Hager-Theodorides AL Bone morphogenetic protein 2/4 signaling regulates early thymocyte differentiation J Immunol 2002 169 5496 5504 12421925
  17. [18]Takahama Y Journey through the thymus: stromal guides for T-cell development and selection Nat Rev Immunol 2006 6 127 135 16491137
  18. [19]Rodewald HR Kretzschmar K Swat W Takeda S Intrathymically expressed c-kit ligand (stem cell factor) is a major factor driving expansion of very immature thymocytes in vivo Immunity 1995 3 313 319 7552996
  19. [20]Lennartsson J Ronnstrand L Stem cell factor receptor/c-Kit: from basic science to clinical implications Physiol Rev 2012 92 1619 1649 23073628
  20. [21]Gray DH Chidgey AP Boyd RL Analysis of thymic stromal cell populations using flow cytometry J Immunol Methods 2002 260 15 28 11792372
  21. [22]Red-Horse K Ueno H Weissman IL Krasnow MA Coronary arteries form by developmental reprogramming of venous cells Nature 2010 464 549 553 20336138 PMC2924433
  22. [23]Brannan CI Steel-Dickie mutation encodes a c-kit ligand lacking transmembrane and cytoplasmic domains Proc Natl Acad Sci U S A 1991 88 4671 4674 1711207 PMC51727
  23. [24]Flanagan JG Chan DC Leder P Transmembrane form of the kit ligand growth factor is determined by alternative splicing and is missing in the Sld mutant Cell 1991 64 1025 1035 1705866
  24. [25]Gu Y Runyan C Shoemaker A Surani MA Wylie C Membrane-bound steel factor maintains a high local concentration for mouse primordial germ cell motility, and defines the region of their migration PLoS One 2011 6 e25984 21998739 PMC3188585
  25. [26]Mikkelsen HB Malysz J Huizinga JD Thuneberg L Action potential generation, Kit receptor immunohistochemistry and morphology of steel-Dickie (Sl/Sld) mutant mouse small intestine Neurogastroenterol Motil 1998 10 11 26 9507248
  26. [27]Kapur R Signaling through the interaction of membrane-restricted stem cell factor and c-kit receptor tyrosine kinase: genetic evidence for a differential role in erythropoiesis Blood 1998 91 879 889 9446648
  27. [28]Russell ES Hereditary anemias of the mouse: a review for geneticists Adv Genet 1979 20 357 459 390999
  28. [29]Kisanuki YY Tie2-Cre transgenic mice: a new model for endothelial cell-lineage analysis in vivo Dev Biol 2001 230 230 242 11161575
  29. [30]Claxton S Efficient, inducible Cre-recombinase activation in vascular endothelium Genesis 2008 46 74 80 18257043
  30. [31]Srinivas S Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus BMC Dev Biol 2001 1 4 11299042 PMC31338
  31. [32]Gordon J Specific expression of lacZ and cre recombinase in fetal thymic epithelial cells by multiplex gene targeting at the Foxn1 locus BMC Dev Biol 2007 7 69 17577402 PMC1906761
  32. [33]Calderon L Boehm T Synergistic, context-dependent, and hierarchical functions of epithelial components in thymic microenvironments Cell 2012 149 159 172 22464328
  33. [34]Krause DS Scadden DT Deconstructing the complexity of a microenvironmental niche Cell 2012 149 16 17 22464318 PMC3652249
  34. [35]Ramasamy SK Kusumbe AP Adams RH Regulation of tissue morphogenesis by endothelial cell-derived signals Trends Cell Biol 2014 PMC4943524 25529933
  35. [36]Sasaki T Regulation of hematopoietic cell clusters in the placental niche through SCF/Kit signaling in embryonic mouse Development 2010 137 3941 3952 20980401
  36. [37]Ding L Saunders TL Enikolopov G Morrison SJ Endothelial and perivascular cells maintain haematopoietic stem cells Nature 2012 481 457 462 22281595 PMC3270376
  37. [38]Badea TC Wang Y Nathans J A noninvasive genetic/pharmacologic strategy for visualizing cell morphology and clonal relationships in the mouse J Neurosci 2003 23 2314 2322 12657690 PMC6742025
  38. [39]Moreira PN Pozueta J Giraldo P Gutierrez-Adan A Montoliu L Generation of yeast artificial chromosome transgenic mice by intracytoplasmic sperm injection Methods Mol Biol 2006 349 151 161 17071981
  39. [40]Farley FW Soriano P Steffen LS Dymecki SM Widespread recombinase expression using FLPeR (flipper) mice Genesis 2000 28 106 110 11105051
  40. [41]Schindelin J Fiji: an open-source platform for biological-image analysis Nat Methods 2012 9 676 682 22743772 PMC3855844
  41. [42]Ramskold D Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells Nat Biotechnol 2012 30 777 782 22820318 PMC3467340
  42. [43]Kim D TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions Genome Biol 2013 14 R36 23618408 PMC4053844
  43. [44]Grover A Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate J Exp Med 2014 211 181 188 24493804 PMC3920567

Cited by

Sorted by citations

Authors
Buono, M., Facchini, R., Matsuoka, S., Thongjuea, S., Waithe, D., Luis, T. C., Giustacchini, A., Besmer, P., Mead, A. J., Jacobsen, S. E. W., & Nerlov, C.
Affiliations
  • University of Oxford (GB)
  • Memorial Sloan Kettering Cancer Center (US)
Corresponding author
  • Jacobsen, Sten Eirik W.
  • Nerlov, Claus
ORCID
Venue
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2016-01-18
Volume
18
Issue
2
Pages
157-167
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
DOI
10.1038/ncb3299
PMC
PMC4972409
OpenAlex
W2272711685
Cited by
79
References
1
Citations by year
2026: 2 · 2025: 8 · 2024: 11 · 2023: 10 · 2022: 9 · 2021: 6 · 2020: 8 · 2019: 5 · 2018: 8 · 2017: 7 · 2016: 5
FWCI
5.05
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Cancer Research UK (A11814)
  • Medical Research Council (MR/K01577X/1, MR/M00919X/1, MR/L006340/1)
  • National Heart, Lung, and Blood Institute (R01HL055748)
  • National Cancer Institute (R01CA102774, P30CA008748)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD038908)
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
T cell development, thymic niche, stem cell factor, CD117, vascular endothelial cells, cortical thymic epithelial cells, thymic cortex, T cell differentiation
MeSH terms
Animals, Cell Differentiation, Cell Movement, Cells, Cultured, Mice, Transgenic, Phenotype, Signal Transduction, Gene Expression Regulation, Developmental, Coculture Techniques, Cell Lineage, Stem Cell Factor, Paracrine Communication, Multipotent Stem Cells, Endothelial Cells, Stem Cell Niche, Thymocytes

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review