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Single-cell RNA sequencing reveals the molecular features of peripheral blood immune cells in children, adults and centenarians

ABSTRACT: The molecular and functional characteristics of peripheral blood immune cells in childhood may contribute to the specialized immune system in children. At present, few researches have compared immune cells in childhood with other age groups, and there is a lack of understanding of immune cells in childhood from the whole lifespan. To display the molecular characteristics of peripheral blood immune cells in childhood at the single-cell level, we performed a comparative study by constructing a peripheral blood mononuclear cell (PBMC) atlas of multiple age groups, including children, young adults, middle-aged adults, aged adults and supercentenarians. The atlas revealed that monocytes in childhood were markedly different from those in other periods. B cells in childhood had a greater ability to respond to viruses and to activate mast cells. Remarkably, we identified a new subtype of CD8+ cytotoxic T cells expressing both naïve and cytotoxicity genes specifically in childhood. The marker genes of this subtypes were used as marker proteins for flow cytometry analysis, and the results confirmed the findings of the scRNA-seq. Moreover, there was more frequent crosstalk between PBMCs in childhood than in other periods, which may be one of the characteristics of the immune system in childhood. Finally, the differences in the expression of susceptibility genes in the PBMCs of different age groups may indicate differences in the disease spectrum of different age groups. In conclusion, this research systematically described the molecular characteristics of peripheral blood immune cells in childhood from multiple levels, and provided new evidence to elucidate the special immune environment of childhood.

ORGANISM(S): Homo sapiens

PROVIDER: GSE206295 | GEO | 2022/12/30

REPOSITORIES: GEO

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Project description:DNA methylation (DNAm) plays diverse roles in human biology, but this dynamic epigenetic mark remains far from fully characterized. Although earlier studies uncovered loci that undergo age-associated DNAm changes in adults, little is known about such changes during childhood. Despite profound DNAm plasticity during embryogenesis and early development, monozygotic twins show indistinguishable childhood methylation, suggesting DNAm is highly coordinated during the pediatric period. Here we examine the methylation of 27,578 CpG dinucleotides in peripheral blood DNA from 398 boys, aged 3 to 17 years, and find significant age-associated changes in DNAm at 2,078 loci. We report a deficit of such loci on the X chromosome, a preference for specific nucleotides immediately surrounding the interrogated CpG dinucleotide, and a primary association with developmental and immune ontological functions. These pediatric age-associated loci overlap significantly with those previously identified in adults (p < 0.001) but most of the pediatric loci are unique, suggesting many are childhood-specific. Meta-analysis (n = 1080) with two adult studies reveals that the methylation changes in 29.5% of the age-associated pediatric loci follow a linear pattern from childhood into adulthood; however, we also find a three-fold higher rate of change in children compared with adults and that a higher proportion of lifelong changes are more accurately modeled as a function of logarithmic age. We therefore conclude that DNAm changes occur more rapidly during childhood and are imperfectly accounted for by statistical corrections that are linear in age, further suggesting that future DNAm studies are matched closely for age. Age associated DNA methylation was evaluated at each CpG locus using a fixed-effects linear regression model adjusting for BeadChip as a covariate to account for batch effects. Analysis of variance (ANOVA) was conducted for each CpG locus to assess the age affect at each CpG locus which was subsequently corrected for multiple hypotheses using a Benjamini-Hochberg FDR. SUPPLEMENTARY FILES: * Matrix_AllSampleDetection.txt: Detection P-values for each sample and each loci * Matrix_AllSampleSignal.txt: Signal for Probe A and Probe B for each sample and each loci * Matrix_Non-Normalized_AllSampleBeta.txt: Beta values calculated using GenomeStudio v2010.3 Methylation Module 1.8.5 as Signal of Probe B / (Signal of Probe A + Signal of Probe B + 100) * Matrix_Normalized_AllSampleBetaPrime.txt: Beta Prime values used for analysis calculated from the Probe B and Probe A signals as Beta Prime = Signal of Probe B / (Signal of Probe A + Signal of Probe A)

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Single-cell RNA sequencing reveals the molecular features of peripheral blood immune cells in children, adults and centenarians

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