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The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus.

Publication ,  Journal Article
Karimi, MM; Guo, Y; Cui, X; Pallikonda, HA; Horková, V; Wang, Y-F; Gil, SR; Rodriguez-Esteban, G; Robles-Rebollo, I; Bruno, L; Georgieva, R ...
Published in: Nat Commun
January 4, 2021

CD4 and CD8 mark helper and cytotoxic T cell lineages, respectively, and serve as coreceptors for MHC-restricted TCR recognition. How coreceptor expression is matched with TCR specificity is central to understanding CD4/CD8 lineage choice, but visualising coreceptor gene activity in individual selection intermediates has been technically challenging. It therefore remains unclear whether the sequence of coreceptor gene expression in selection intermediates follows a stereotypic pattern, or is responsive to signaling. Here we use single cell RNA sequencing (scRNA-seq) to classify mouse thymocyte selection intermediates by coreceptor gene expression. In the unperturbed thymus, Cd4+Cd8a- selection intermediates appear before Cd4-Cd8a+ selection intermediates, but the timing of these subsets is flexible according to the strength of TCR signals. Our data show that selection intermediates discriminate MHC class prior to the loss of coreceptor expression and suggest a model where signal strength informs the timing of coreceptor gene activity and ultimately CD4/CD8 lineage choice.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

January 4, 2021

Volume

12

Issue

1

Start / End Page

99

Location

England

Related Subject Headings

  • Transcription Factors
  • Thymus Gland
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • RNA, Messenger
  • Principal Component Analysis
  • Mice, Inbred C57BL
  • Mice
  • Lymphocyte Activation
  • Histocompatibility Antigens
 

Citation

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Karimi, M. M., Guo, Y., Cui, X., Pallikonda, H. A., Horková, V., Wang, Y.-F., … Merkenschlager, M. (2021). The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus. Nat Commun, 12(1), 99. https://doi.org/10.1038/s41467-020-20306-w
Karimi, Mohammad M., Ya Guo, Xiaokai Cui, Husayn A. Pallikonda, Veronika Horková, Yi-Fang Wang, Sara Ruiz Gil, et al. “The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus.Nat Commun 12, no. 1 (January 4, 2021): 99. https://doi.org/10.1038/s41467-020-20306-w.
Karimi MM, Guo Y, Cui X, Pallikonda HA, Horková V, Wang Y-F, et al. The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus. Nat Commun. 2021 Jan 4;12(1):99.
Karimi, Mohammad M., et al. “The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus.Nat Commun, vol. 12, no. 1, Jan. 2021, p. 99. Pubmed, doi:10.1038/s41467-020-20306-w.
Karimi MM, Guo Y, Cui X, Pallikonda HA, Horková V, Wang Y-F, Gil SR, Rodriguez-Esteban G, Robles-Rebollo I, Bruno L, Georgieva R, Patel B, Elliott J, Dore MH, Dauphars D, Krangel MS, Lenhard B, Heyn H, Fisher AG, Štěpánek O, Merkenschlager M. The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus. Nat Commun. 2021 Jan 4;12(1):99.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

January 4, 2021

Volume

12

Issue

1

Start / End Page

99

Location

England

Related Subject Headings

  • Transcription Factors
  • Thymus Gland
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • RNA, Messenger
  • Principal Component Analysis
  • Mice, Inbred C57BL
  • Mice
  • Lymphocyte Activation
  • Histocompatibility Antigens