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Series GSE186049 Query DataSets for GSE186049
Status Public on Oct 18, 2022
Title Pre-T cell receptor Self-MHC Sampling Restricts Thymocyte Dedifferentiation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Other
Summary Programming T lymphocytes to distinguish self from non-self is a vital, multi-step process arising in the thymus. Signalling through the pre-T cell receptor (preTCR), a CD3-associated heterodimer comprising an invariant pTα chain and a clone-specific β chain, constitutes a critical early checkpoint in thymocyte development within the αβ T-cell lineage. Recent work demonstrates that preTCRs arrayed on double negative (DN) thymocytes, like αβ TCRs appearing on double positive (DP) thymocytes, ligate peptides bound to MHC molecules (pMHC) on thymic stroma but via a different molecular docking strategy. Here we show the consequences of those distinctive interactions for thymocyte progression, using synchronized fetal thymic progenitor cultures differing in the presence or absence of pMHC on support stroma, determining single cell transcriptomes at key thymocyte developmental transitions. Although MHC negative stroma fosters αβ T lymphocyte differentiation, the absence of pMHC-preTCR interplay leads to deviant thymocyte transcriptional programming associated with de-differentiation. Highly proliferative DN and DP subsets with antecedent characteristics of T cell lymphoblastic and myeloid malignancies emerge. Thus, in addition to fostering β chain repertoire broadening for subsequent αβ TCR utilization, preTCR-pMHC interaction limits cellular plasticity to facilitate normal thymocyte differentiation and proliferation that, if absent, introduces significant developmental vulnerabilities.
 
Overall design Transcriptional profiling of early thymocytes developing in the presence or absence of peptide-MHC
 
Contributor(s) Duke-Cohan JS, Akitsu A, Mallis RJ, Messier CM, Lizotte PH, Hwang W, Lang MJ, Reinherz EL
Citation(s) 36410718
Submission date Oct 18, 2021
Last update date Jan 17, 2023
Contact name Jonathan S. Duke-Cohan
E-mail(s) Jonathan_Duke-Cohan@dfci.harvard.edu
Phone +1-617-632-3122
Organization name Dana-Farber Cancer Institute
Department Medical Oncology
Lab Immunobiology
Street address 450 Brookline Avenue JF517
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (18)
GSM5629779 MHC+ DN3a transcripts (file prefix: PDN3a_)
GSM5629780 MHC+ DN3b transcripts (file prefix: PDN3b_)
GSM5629781 MHC+ DN4 transcripts (file prefix: PDN4_)
Relations
BioProject PRJNA772188
SRA SRP341932

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE186049_2021-09-02-Duke-Cohan-File-1-MHCpos-GEX-all-libraries-all-clusters.xlsx 19.1 Mb (ftp)(http) XLSX
GSE186049_2021-09-02-Duke-Cohan-File-2-MHCneg-GEX-all-libraries-all-clusters.xlsx 19.6 Mb (ftp)(http) XLSX
GSE186049_2021-09-02-Duke-Cohan-File-3-OP9-DL4-MHCpos-MHCneg.xlsx 5.0 Mb (ftp)(http) XLSX
GSE186049_RAW.tar 527.7 Mb (http)(custom) TAR (of CSV, MTX, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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