Global transcriptional analysis of primitive thymocytes reveals accelerated dynamics of T cell specification in fetal stages.

Immunogenetics
Nikolai N BelyaevAlexandre J Potocnik

Abstract

T cell development constitutes a multistage process allowing the dissection of events resulting in cellular commitment and functional specification in a specialized microenvironment. This process is guided by the appropriate expression of regulatory genetic factors like transcriptional activators or repressors which are, in part, dependent on instructive signals of the microenvironment. To date, it remains unclear whether exactly the same genetic mechanism acts in adult compared to fetal T cell development. In order to directly compare T cell commitment during adult and fetal differentiation, we isolated subsequent stages of intrathymic subpopulations starting with early canonical T cell progenitors up to irreversibly committed T cell precursors. The genome-wide analysis revealed several distinct gene clusters with a specific pattern of gene regulation for each subset. The largest cluster contained genes upregulated after transition through the most primitive pool into the next transitory population with a consistently elevated expression of elements associated with ongoing T cell fate specification, like Gata3 and Tcf7, in fetal progenitors. Furthermore, adult and fetal T cell progenitors occupied distinct "transcriptional ter...Continue Reading

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Citations

Dec 10, 2013·Nature Immunology·Cyrille RamondAna Cumano
Jul 26, 2014·Nature Reviews. Immunology·Mary A Yui, Ellen V Rothenberg
Jul 19, 2017·Cold Spring Harbor Perspectives in Biology·Hiroyuki Hosokawa, Ellen V Rothenberg
Feb 14, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Encarnacion Montecino-RodriguezKenneth Dorshkind
Aug 7, 2018·The Journal of Clinical Investigation·Changshan WangGoro Sashida

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Datasets Mentioned

BETA
GSE24142

Methods Mentioned

BETA
flow cytometry
fluorescence activated cell sorter
in vitro transcription
PCR
chip
fluorescence-activated cell sorter
FACS

Software Mentioned

Genespring GX
GeneChip Operating Software ( GCOS )
FlowJo
Agilent GeneSpring GX

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