Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Single-cell analysis of T-cells from mouse neonate thymuses in a wild type control and a placental specific isoform of Igf2 knock-down (igf2-P0)

ABSTRACT: Fetal growth restriction (FGR) causes a wide variety of developmental defects in the neonate which can lead to heart disease, diabetes, anxiety and other disorders later in life. The effect of FGR on the immune system, however, is poorly understood. Immune cells throughout development are identified using cell-surface markers to distinguish between subtly different stages. These (surface) proteins, however, do not necessarily generate differences in cellular activity and may thus be only a coincidental shallow guide to classifying cells. High-throughput single-cell transcriptomics using DropSeq was performed on mouse neonate thymuses. The T-cell population was selected through flow cytometry in wild type controls and a placental specific isoform of Igf2 knock-down (igf2-p0). Using this analysis, we discovered skewed T-cell populations in the growth restricted murine neonate indicating a developmental delay. This finding recapitulates the altered immunity found in growth restricted human infants. The T-cell deficit persisted into adulthood, even when body and organ weights approached normal levels due to catch-up growth. This reduction in T-cellularity may have significant implications in adult immunity, adding to the wide variety of fetal origins for adult disease already known.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Mus musculus

SUBMITTER: Wendi Bacon

PROVIDER: E-MTAB-6945 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Background and aims: Metabolic diseases, including diabetes, obesity, and dyslipidemia, are significant public health concerns worldwide. The insulin-like growth factor 2 (IGF2) gene have been implicated in various physiological processes, but its specific role in lipid metabolism remains unclear. We aim to elucidate the role of IGF2 in regulating lipid metabolism in adipose tissues and its association with metabolic syndrome (MetS). Methods: The research employed a multidisciplinary approach to investigate the role of IGF2 in lipid metabolism. We investigated the correlation between genetic variations within the IGF2 gene and metabolic parameters. We conduct a cross-sectional human study to evaluate relationships between varying IGF2 serum concentrations and the incidence of MetS. Additionally, manipulation of IGF2 expression levels in mouse and cell models via overexpression and knockdown to assess impacts on lipid metabolism in adipose tissue, specifically lipid accumulation, insulin resistance, and the balance between lipogenesis and lipolysis. Furthermore, the study employs metabolomics techniques to scrutinize the broader metabolic profiles in adipose tissues in response to IGF2 modulation. Results: Multiple SNP loci in the IGF2 gene were significantly associated with BMI, HbA1c, and diabetes. Insufficient or excessive expression of IGF2 was identified as a risk factor for hyperlipidemia, low HDL-c, and central obesity in MetS. We observed that IGF2 was mainly concentrated in adipose tissues and adipocytes. Enhanced IGF2 expression stimulated adipogenesis and lipid accumulation, whereas IGF2 knockdown hindered lipolysis, exacerbating ectopic lipid accumulation and insulin resistance. There is a substantial enlargement of pancreatic tissue and heightened insulin generation in mice deficient in IGF2. Activation of the PI3K/Akt pathway through IGF1R in IGF2 excess or INSR in conditions of IGF2 scarcity, along with inhibition of AMPK, implies a common downstream process that favors lipid accumulation and metabolic reprogramming in adipocytes. Conclusions: Our study demonstrated that upregulation of IGF2 enhanced adipogenesis and lipogenesis, while knockdown of IGF2 inhibited lipolysis, which resulting in accelerating lipid accumulation through PI3K/Akt-AMPK pathway.

Dataset Information

Single-cell analysis of T-cells from mouse neonate thymuses in a wild type control and a placental specific isoform of Igf2 knock-down (igf2-P0)

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets