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Dynamic 3'UTR changes during naïve CD4+ T cell activation and proliferation are reverted in the effector/memory state

ABSTRACT: Dynamic 3'UTR changes during naïve CD4+ T cell activation and proliferation are reverted in the effector/memory state

PROVIDER: PRJNA861662 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15719703.fastq.gz	Fastqsanger.gz
	SRR15719704.fastq.gz	Fastqsanger.gz
	SRR15719705.fastq.gz	Fastqsanger.gz
	SRR15719706.fastq.gz	Fastqsanger.gz
	SRR15719707.fastq.gz	Fastqsanger.gz

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Dynamic 3'UTR changes during naïve CD4+ T cell activation and proliferation are reverted in the effector/memory state [Iso-Seq]

Project description:3’ untranslated regions (3’UTRs) are critical elements of most messenger RNAs: they contain binding sites for RNA-binding proteins (RBP) and microRNAs that affect various aspects of the RNA life cycle including transcript stability. In response to T cell receptor activation, T cells undergo massive expansion during the effector phase of the immune response and dynamically modify their 3’UTRs. Whether this serves to directly regulate the abundance of specific mRNAs or is a secondary effect of proliferation remains unclear. To study 3’UTR dynamics in T helper cells we investigated division-dependent alternative polyadenylation (APA). We generated 3’ end UTR sequencing in naïve, 48h activated (anti-CD3/CD28 cultured), memory and regulatory CD4+ Tcells. 48h activated Tcells were CTV-separated into three populations: cells not yet divided, divided once and twice. 3’UTR length changes were estimated using non-negative matrix factorization approach and partially compared with long-read PacBio sequencing. We found that, in T helper cells, APA events were transient and reverted after effector phase expansion. Using an orthogonal bulk RNAseq dataset, we found that APA genes were not significantly associated with either post-transcriptional or transcriptional regulation, differential gene expression or transcript usage, demonstrating a marginal effect of APA on transcript abundance. 3’UTR sequence analysis revealed conserved binding sites for important microRNAs and RBPs co-evolving with APA events. These results highlight the important role of polyA site usage in the control of cell fate decisions and homeostasis.

2023-11-06 | GSE209603 | GEO

Dynamic 3'UTR changes during naïve CD4+ T cell activation and proliferation are reverted in the effector/memory state [A-Seq]

Project description:3’ untranslated regions (3’UTRs) are critical elements of most messenger RNA species and can contain binding sites for RNA-binding proteins (RBP) and microRNAs that affect various aspects of RNA life cycles including transcript stability. Cells of the adaptive immune system undergo massive expansion during the effector phase of the immune response and dynamically modify their 3’UTRs in a response to T cell receptor activation. Whether this phenomenon is a secondary effect of proliferation or a mechanism to directly regulate the abundance of specific mRNAs remains unclear. To study 3’UTR dynamics in T helper cells we investigated division-dependent alternative polyadenylation and observed a transient character of global 3’UTR shortening/lengthening in T helper cells that return to a naïve-like polyadenylation state after effector phase expansion. We also showed that 3’UTR lengthening is associated with higher transcript abundance and post-transcriptional regulation than 3’UTR shortening. Sequence analysis of conserved microRNA and RBP binding sites located within varying 3’ UTR regions highlighted the putative involvement of several microRNAs during this process. Our study emphasizes the value of polyadenylation isoforms analysis for understanding cell behaviors, revealing new aspects of the highly complex interplay of transcriptional and post-transcriptional layers in triggering transcript abundance.

2023-11-06 | GSE183424 | GEO

Dynamic 3'UTR changes during naïve CD4+ T cell activation and proliferation are reverted in the effector/memory state [Iso-Seq]

Project description:Dynamic 3'UTR changes during naïve CD4+ T cell activation and proliferation are reverted in the effector/memory state [Iso-Seq]

| PRJNA861663 | ENA

Dynamic 3'UTR changes during naïve CD4+ T cell activation and proliferation are reverted in the effector/memory state [A-Seq]

Project description:Dynamic 3'UTR changes during naïve CD4+ T cell activation and proliferation are reverted in the effector/memory state [A-Seq]

| PRJNA760766 | ENA

Dynamic 3'UTR changes during naïve CD4+ T cell activation and proliferation are reverted in the effector/memory state

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-11-06 | GSE209604 | GEO

Neonatal naïve CD8+ T cells have effector-like gene expression that prevents memory cell formation [3'UTR-seq]

Project description:Neonates are intrinsically defective at creating memory CD8+ T cells in response to infection with intracellular pathogens. Here we investigated differential of small RNAs, transcription factors, and chemokine receptors regulation in neonates as compared to adults before and during infection. We found that prior to infection, naïve cells have a different expression profile for many microRNAs, and gene targets of these microRNAs show widespread expression differences. These targets and other changes in gene expression in naïve cells result in neonatal cells that get activated more easily, express chemokine receptors that home to sites of infection, and are less protected from apoptosis during contraction. As a result, changes in neonatal naïve cells drive effector cell terminal differentiation at the expense of creating long-lived memory cells. PolyA RNA was selected and sequenced from adult and neonatal CD8+ T cells before and during infection

2015-09-24 | E-GEOD-65921 | biostudies-arrayexpress

Neonatal naïve CD8+ T cells have effector-like gene expression that prevents memory cell formation [3'UTR-seq]

2015-09-24 | GSE65921 | GEO

AMPK signaling for naïve pluripotency [Hs]

Project description:We show activation of AMP kinase (AMPK) with single chemical compounds can endow naïve pluripotency. AMPK activators reverted early-stage differentiating cells or epi-stem cells to naïve state. Moreover, AMPK activators reverted human ESCs to naïve state with pluripotent gene expression profiles and X-chromosome reactivation.

2019-03-30 | GSE92725 | GEO

AMPK signaling for naïve pluripotency [Mm]

2019-03-30 | GSE92441 | GEO

Effector cells derived from naïve or central memory pmel-1 CD8+ T cells

Project description:Effector cells for adoptive immunotherapy can be generated by in vitro stimulation of naïve or memory subsets of CD8+ T cells. While the characteristics of CD8+ T cell subsets are well defined, the heritable influence of those populations on their effector cell progeny is not well understood. We studied effector cells generated from naïve or central memory CD8+ T cells and found that they retained distinct gene expression signatures and developmental programs. Effector cells derived from central memory cells tended to retain their CD62L+ phenotype, but also to acquire KLRG1, an indicator of cellular senescence. In contrast, the effector cell progeny of naïve cells displayed reduced terminal differentiation, and, following infusion, they displayed greater expansion, cytokine production, and tumor destruction. These data indicate that effector cells retain a gene expression imprint conferred by their naïve or central memory progenitors, and they suggest a strategy for enhancing cancer immunotherapy.

2009-06-10 | GSE16522 | GEO

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