CaltechAUTHORS
  A Caltech Library Service

Fine-Scale Staging of T Cell Lineage Commitment in Adult Mouse Thymus

Yui, Mary A. and Feng, Ni and Rothenberg, Ellen V. (2010) Fine-Scale Staging of T Cell Lineage Commitment in Adult Mouse Thymus. Journal of Immunology, 185 (1). pp. 284-293. ISSN 0022-1767. PMCID PMC4091773. http://resolver.caltech.edu/CaltechAUTHORS:20100630-085544779

[img] PDF - Accepted Version
See Usage Policy.

1693Kb

Use this Persistent URL to link to this item: http://resolver.caltech.edu/CaltechAUTHORS:20100630-085544779

Abstract

T cell development is marked by the loss of alternative lineage choices accompanying specification and commitment to the T cell lineage. Commitment occurs between the CD4 and CD8 double-negative (DN) 2 and DN3 stages in mouse early T cells. To determine the gene regulatory changes that accompany commitment, we sought to distinguish and characterize the earliest committed wild-type DN adult thymocytes. A transitional cell population, defined by the first downregulation of surface c-Kit expression, was found to have lost the ability to differentiate into dendritic cells and NK cells when cultured without Notch-Delta signals. In the presence of Notch signaling, this subset generates T lineage descendants in an ordered precursor–product relationship between DN2, with the highest levels of surface c-Kit, and c-Kit–low DN3 cells. These earliest committed cells show only a few differences in regulatory gene expression, compared with uncommitted DN2 cells. They have not yet established the full expression of Notch-related and T cell differentiation genes characteristic of DN3 cells before β selection. Instead, the downregulation of select stem cell and non-T lineage genes appears to be key to the extinction of alternative lineage choices.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.4049/jimmunol.1000679 DOIArticle
http://www.jimmunol.org/cgi/content/abstract/185/1/284PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091773/PubMed CentralArticle
ORCID:
AuthorORCID
Yui, Mary A.0000-0002-3136-2181
Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:© 2010 by The American Association of Immunologists, Inc. Received for publication February 26, 2010. Accepted for publication April 25, 2010. This work was supported by National Institutes of Health Grant R01 AI064590 (to M.A.Y.), the Louis A. Garfinkle Memorial Laboratory Fund, the Al Sherman Foundation, and the Albert Billings Ruddock Professorship (to E.V.R.).
Funders:
Funding AgencyGrant Number
NIHR01 AI064590
Louis A. Garfinkle Memorial Laboratory FundUNSPECIFIED
Al Sherman FoundationUNSPECIFIED
Albert Billings Ruddock ProfessorshipUNSPECIFIED
PubMed Central ID:PMC4091773
Record Number:CaltechAUTHORS:20100630-085544779
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20100630-085544779
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:18867
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:03 Aug 2010 23:18
Last Modified:24 Jul 2017 19:59

Repository Staff Only: item control page