Dynamic expression of Erg controls fetal-to-adult maturation of the hematopoietic system [ChIP-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE269350 | GEO | 2025/11/20
REPOSITORIES: GEO
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Project description:Adults and children are affected by different types of blood diseases. We hypothesize that this is due to differences in normal blood formation between infants, children, and adults. Our laboratory focuses on understanding these age-related differences in blood formation as a foundation upon which to improve understanding of blood diseases. In this project, we extend our previous work to understand how hallmarks of young versus mature blood formation – for example, the types of mature blood cells produced – are controlled at the genetic level. I will use a combination of mouse models, genetic manipulation, and genetic profiling to test our hypothesis that the key blood stem cell factor Erg controls the age state of blood formation.
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2020-04-20 | GSE148815 | GEO
Project description:The airway epithelium is a key protective barrier whose integrity is preserved by the self-renewal and differentiation of basal progenitor cells. Epithelial cells are central to the pathogenesis of multiple chronic lung diseases for which age is a principle risk factor. Children are also less susceptible to SARS-CoV-2 infection, suffer less severe symptoms than adults and have a lower rate of mortality. Few studies have addressed differences between airway epithelial cells in children and adults. Here, we perform bulk RNA sequencing studies in laser-captured whole epithelium, FACS-sorted basal cells and cultured basal cells, as well as in vitro cell proliferation experiments, to address the intrinsic molecular differences between paediatric and adult airway basal cells. We find that, while the cellular composition of the paediatric and adult tracheal epithelium is broadly similar, in cell culture, paediatric airway epithelial cells displayed higher colony forming ability, better in vitro growth and outcompeted adult cells in competitive proliferation assays. Although recurring differences between airway epithelial gene expression were seen between samples from children and adults, RNA sequencing showed broad conservation of transcriptional programmes. Genes associated with SARS-CoV-2 infection were not differentially expressed between children and adults, although individuals showed some variability in their expression of viral infection-associated genes. Our results chart important cell intrinsic differences in transcriptional profile and regenerative capacity between tracheal epithelial cells of children and adults.
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2024-12-02 | GSE270553 | GEO
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Project description:Genome wide DNA methylation profiling of isolated monocyte samples from healthy Kenyan children, the same children during an episode of acute malaria, healthy Kenyan adults, and healthy adults from the United States. The Illumina Infinium MethylationEPIC BeadChip microarray was used to obtain DNA methylation profiles across approximately 860,000 CpGs in negatively selected monocyte samples. Samples included monocytes from 8 children from western Kenya obtained while healthy and matching samples from the same 8 Kenyan children obtained during an episode of acute uncomplicated Plasmodium falciparum malaria, 8 healthy malaria-immune adults from western Kenya, and 8 healthy malaria-naive adults from the US. Abstract -- Background: Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results: We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions: These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.
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