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B2M knockout for hypo-immunity alters the global profiles of membrane-proteins and cytokines and impairs therapeutic efficacy of human stem cells

ABSTRACT: B2M knockout for hypo-immunity alters the global profiles of membrane-proteins and cytokines and impairs therapeutic efficacy of human stem cells

PROVIDER: PRJNA1216542 | ENA |

REPOSITORIES: ENA

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B2M knockout for hypo-immunity alters the global profiles of membrane-proteins and cytokines and impairs therapeutic efficacy of human stem cells

Project description:β2-microglobulin (B2M) is the light chain subunit of type I human leukocyte antigen complexes that play a key role in the immune system. Genetic knockout (KO) of B2M in human pluripotent stem cells (hPSCs) has been used as a major approach together with many other strategies to generate hypo-immunogenic, universal stem cells for allogeneic cell transplantation without triggering immune rejection. However, this approach assumes that B2M is dispensable for stem cell differentiation and therapy, although it lacks evidence from thorough evaluation. Here, we conducted genome-wide analyses of isogenic pairs of wild-type (WT) and B2M-KO hESCs and their derived mesenchymal stem cells (E-MSCs), which revealed proteomic and transcriptomic alternations due to the KO. Over 200 proteins were mistargeted from the plasma membranes of B2M-KO hESCs and E-MSCs, suggesting that B2M is crucial for protein trafficking in the subcellular organelles. The expression of osteo-chondrogenic determinants and inflammation-related cytokines differed dramatically in B2M-KO E-MSCs from WT E-MSCs, consistent with the impaired osteogenic differentiation and wound-healing efficacy of B2M-KO E-MSCs. This study reveals previously unrecognized functions of B2M, which alerts cautions be used when applying B2M-KO cells to therapy.

2025-02-04 | GSE288189 | GEO

HCV Hypo- vs. Hyper-Phosphorylated NS5A Interactome

Project description:Chronic hepatitis C virus (HCV) infection is a leading cause of liver cancer. HCV propagation and oncogenicity depend in part on the phosphorylation states of its non-structural protein 5A (NS5A); however, little is known about how hypo- or hyper-phosphorylated NS5A functions. Here, we segregated hypo- from hyper-phosphorylated NS5A in HCV-infected Huh7.5.1 cells with two custom-made specific antibodies and differentiated their interacting proteins with dimethyl labeling-based quantitative proteomics. Bioinformatics analysis revealed that hyper-phosphorylated NS5A preferentially binds the polymerase II-associated factor 1 complex known to alter host gene expression involved in cancer progression. In contrast, hypo-phosphorylated NS5A binds proteins involved in host antiviral response. Moreover, we found that the hypo-phosphorylated NS5A binds DNA-dependent protein kinase catalytic subunit (DNA-PKcs) predicted to phosphorylate NS5A at serine 232, a key amino acid that governs NS5A transition from hypo- to hyper-phosphorylation state. Inhibition of DNA-PKcs with an inhibitor or via gene-specific knockdown significantly reduced serine 232 phosphorylation and NS5A hyper-phosphorylation. Collectively, we have identified a protein kinase that regulates a delicate balance of NS5A between hypo- and hyper-phosphorylation states respectively involved in host antiviral responses and liver cancer progression.

2019-06-17 | PXD012767 | Pride

ChIP-Seq Analysis of Eed hypo/wt

Project description:ChIP-Seq Analysis of Eed hypo/wt

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ImmGen Cytokines: Interferons

Project description:ImmGen Cytokines: Interferons

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ImmGen cytokines: Signatures of “common γ-chain” family cytokines

Project description:ImmGen cytokines: Signatures of “common γ-chain” family cytokines

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Histones associated with downregulated genes are hypo-acetylated in Huntington’s disease models

Project description:Transcriptional dysregulation plays a major role in the pathology of Huntington's disease (HD). However, the mechanisms causing selective downregulation of genes remain unknown. Histones regulate chromatin structure and thereby control gene expression; recent studies have demonstrated a therapeutic role for histone deacetylase (HDAC) inhibitors in polyglutamine diseases. This study demonstrates that despite no change in overall acetylated histone levels, histone H3 is hypo-acetylated at promoters of downregulated genes in R6/2 mice, ST14a and STHdh cells, as demonstrated by in vivo chromatin immunoprecipitation. In addition, HDAC inhibitor treatment increases association of acetylated histones with downregulated genes and corrects mRNA abnormalities. In contrast, there is a decrease in mRNA levels in wild-type cells following treatment with a histone acetyltransferase inhibitor. Although changes in histone acetylation correlate with decreased gene expression, histone hypo-acetylation may be a late event, as no hypo-acetylation is observed in 4-week-old R6/2 mice. Nevertheless, treatment with HDAC inhibitors corrects mRNA abnormalities through modification of histone proteins and may prove to be of therapeutic value in HD. Keywords: cell type comparison and disease state analysis

2008-05-17 | GSE11358 | GEO

Differentially expressed mRNAs in lungs between hypoxic human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (Hypo-EVs)-INH-treated mice and OVA-induced asthma mice

Project description:To better understand the molecular processes of nebulized Hypo-Evs on asthma intervention, OVA-induced chronic asthma model were established (OVA group), and a therapeutic regimen was instigated by inhaling Hypo-EVs four times (Hypo-EVs group) . Then a global RNA sequencing of mouse lung from the OVA and Hypo-EVs groups was performed.

2023-04-26 | GSE226639 | GEO

Hypo-osmotic shock - ppt1 and wildtype

Project description:Wild type and ppt1 mutant under hypo-osmotic shock. Cultures were grown with 1M sorbitol for ~20 hours, cells were collected by centrifugation and resuspended in YPD at time zero. Samples were collected at 0, 7, 15, 30 and 60 minutes after transfer to YPD. Experimental samples were used to generate Cy5-labeled cDNA probes, whereas mRNA reference pools extracted from cultures of the respective strains grown to early log phase under normal conditions, were used to generate Cy3-labeled cDNA probes. Cy5- and Cy3-labeled probes were hybridized together to microarrays printed with PCR-amplified fragments, representing 6280 of the Saccharomyces cerevisiae ORFs. Keywords: time-course

2003-04-15 | GSE407 | GEO

Transcriptional dysregulation impairs efficacy of neural stem cell activation during aging.

Project description:Transcriptional dysregulation impairs efficacy of neural stem cell activation during aging.

| PRJNA928369 | ENA

Mbnl2 loss alters novel context processing and impairs object recognition memory

Project description:Mbnl2 loss alters novel context processing and impairs object recognition memory

| PRJNA939151 | ENA