The outcome of umbilical cord blood transplantation (UCBT) is compromised by low hematopoietic stem cell (HSC) doses leading to prolonged time to engraftment, delayed immunological reconstitution and late memory T-cell skewing. Exposure of UCB to dimethyl-prostaglandin E2 (dmPGE2) increases HSC in vivo. We determined that exposure of UCB T lymphocytes to dmPGE2 modified Wnt signaling resulting in T cell factor (TCF)-mediated transcription. Wnt signaling upregulated interleukin (IL)-7R and IL-2Rβ, resulting in enhanced survival mediated by the homeostatic cytokines IL-7 and IL-15. dmPGE2 also induced components of the Wnt pathway and Wnt receptors, thereby priming UCB T cells to receive signals via Wnt ligands in vivo. We observed that the Wnt transcription factor TCF7 and its target EOMES were elevated in the T cells of patients who received PGE2-treated UCBs. Consistent with the role of Wnt/β-catenin signaling to induce and maintain naive, memory precursors and long-lived central memory CD8+ cells, these patients also had increased fractions of CD8+CD45RO-CD62L+ plus CD8+CD45RO+CD62L+ subsets encompassing these T-cell populations. These effects of the PGE2/Wnt/β-catenin axis may have significant implications for harnessing immunity in the context of UCBT, where impaired immune reconstitution is associated with late memory T-cell skewing.
The structural features of dinoflagellate nuclei are distinct from those of other eukaryotes in several respects, and the mechanisms of DNA replication and transcription are almost completely unknown. In this study we investigated the structure and organization of the gene coding for luciferase (LCF), the enzyme catalyzing the bioluminescent reaction in the dinoflagellate Gonyaulax polyedra. The genomic lcf sequence, including its flanking regions, were completely determined. The transcription initiation site was identified using primer extension and RNase protection assays. Sequence analysis shows that, like the luciferin-binding protein gene (lbp) from G. polyedra, lcf does not contain introns. Analysis of results from genomic Southern blots, inverse PCR, and sequencing revealed that the lcf gene is organized as tandem repeats in the genome. The spacer region between the lcf genes, which very likely contains the promoter elements necessary for transcription initiation, has no TATA box or other known promoter elements or consensus sequences. However, a conserved sequence motif was identified by comparing the two intergene spacer regions of lcf and the peridinin chlorophyll protein gene, pcp; a novel 13 nt sequence, CGTGAACGCAGTG, which might be a dinoflagellate promoter, was found to be present in both.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.