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Expression data from adult and neonatal human platelets

ABSTRACT: Understanding the underlying mechanisms of the well-established platelet hyporeactivity in neonates, would be of great relevance for both improving the clinical management of neonates, a population with a higher bleeding risk than adults (especially among sick and preterm infants), and getting new insights onto the regulatory mechanisms of platelet biology. Transcriptome analysis is a useful tool to identify mRNA signature affecting platelet function. However, human fetal/neonatal platelet transcriptome analysis has never been reported. Here, we used, for the first time, mRNA expression array to compare the platelet transcriptome changes during development. Microarray analysis was performed in pure platelet RNA obtained from adult and cord blood, using the same platform in two independent laboratories. A high correlation was obtained between arrays results for both adult and neonate platelet samples. There was also a good agreement between our adult results and those previously reported in three different studies. Gene enrichment analysis demonstrated that immunity- and platelet function-related genes are highly expressed in either developmental stage. Remarkably, 201 genes were found to be differentially expressed along development. In particular, neonatal platelets contain higher levels of mRNA that are associated with protein synthesis and processing, while they carry significantly lower levels of genes related with calcium transport/metabolism and cell signaling (including GNAZ). Overall, our results highlight that variations in platelet transcriptome may underline the hypo-functional phenotype of neonatal platelets, and further support the role of platelets in cellular immune response. A better characterization of the platelet transcriptome across development may help to elucidate the implications of transcriptome changes in different pathological conditions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE94292 | GEO | 2017/02/03

SECONDARY ACCESSION(S): PRJNA369260

REPOSITORIES: GEO

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Project description:To understand better the nature of the poor response of human neonates to intracellular pathogens, we evaluated the transcriptome of neonates as compared to adult naÃ¯ve CD8-T cells. A specific transcription signature of the neonatal cells was found, characterized by a lower expression of signalling and CTL functional genes and a high expression of maturation, cell cycle and innate-immunity associated genes. Functional assays demonstrated that neonatal CD8-T cells undergo homeostatic proliferation, transcribe antimicrobial peptides and produce reactive oxygen species. Master transcription factors were found presumably responsible for this specific signature. Genome wide epigenetic studies showed a corresponding chromatin signature for a number of the differentially expressed genes. Altogether our results show that CD8 neonatal T cells have a particular genetic program with functions within the innate immune response, while still undergoing their maturation process. Neonates are highly susceptible to infections by intracellular pathogens, which are a major cause of infant morbidity and mortality. CD8-T cells control intracellular pathogens through cytotoxic mechanisms in an antigen-dependent manner. We found that human neonatal CD8-T cells, as compared to adult lymphocytes, had a distinctive pattern of gene transcription, characterized by the lower expression of genes involved in TCR signalling and cytotoxicity and a high expression of genes involved in cell cycle and innate immunity. Functional studies corroborated that neonatal CD8-T cells are less cytotoxic, transcribe antimicrobial peptides and produce reactive oxygen species. These properties could explain the high sensitivity of neonates to intracellular pathogen infections and outline novel functions of neonatal CD8-T cells. PBMC total RNAs from Adult and Neonate subjects were profiled after hybridization with Agilent SurePrint G3 Human GE 8x60K Microarray. CD8-T cells mRNA were extracted from 8 samples including: 4 Adults and 4 Neonates.

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Expression data from adult and neonatal human platelets

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