GSE125682: Postprandial blood glucose and triglyceride metabolism govern bone marrow stem cell transcriptional regulation, premature aging and rejuvenation.

Gene Expression Data Explorer
Info Gene counts are sourced from ARCHS4, which provides uniform alignment of GEO samples. You can learn more about ARCHS4 and its pipeline here.
Enter gene symbol:

Select conditions below to toggle them from the plot:

GROUP CONDITION SAMPLES
Lineage- Sca-1+ c-Kit+ cells
GSM3580178 GSM3580179
GSM3580180 GSM3580181
GSM3580182 GSM3580183 GSM3580184 GSM3580185
Description

Submission Date: Jan 25, 2019

Summary: The number of circulating endothelial progenitor cells (EPCs) predicts future development of atherosclerotic cardiovascular disease (ASCVD) and is reduced in patients with type 2 diabetes (T2DM) or impaired glucose tolerance (IGT). Recent studies revealed the contribution of tight control of glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), as well as fatty acid oxidation in the regulation of stem cell behavior. In this study, we show that how dysregulated glucose and triglyceride metabolism in T2DM/IGT affects the homeostasis of EPCs, i.e. bone marrow stem/progenitor cells (BMSCs). In our clinical study, consistent with previous reports, the patients with IGT or T2DM showed reduced level of circulating EPCs, as compared normal glucose tolerance. On the other hand, fasting or postprandial hypertriglyceridemia (hTG) itself did not affect the level of circulating EPCs. However, further analysis using single and multiple regression analyses strongly suggested that, in the presence of postprandial hTG, postprandial hyperglycemia exerts devastating effect on EPC homeostasis. We therefore carried out the proof of concept study in mice. Our experimental study revealed that repetitive glucose+lipid (G+L) spikes, but not repetitive glucose (G) spikes or lipid (L) spikes, rapidly upregulated p53 in BMSCs and induced premature aging phenotype of bone marrow cells, i.e. the impairment of BMSC quiescence and function, and myeloid-biased differentiation. Subsequent analysis implicated that p53-mediated augmentation of mitochondrial OXPHOS plays pivotal role for the impairment of BMSC quiescence and function. On the other hand, it is still not clear how repetitive G+L injection induced myeloid-biased differentiation. Because cell-fate decisions are executed by transcription factors in response to extracellular signals, and the best-known function of p53 is as a transcription factor, we asked to what extent repetitive glucose spikes and repetitive glucose+TG spikes affect transcriptional regulation in LSK cells.

GEO Accession ID: GSE125682

PMID: 34533398

Description

Submission Date: Jan 25, 2019

Summary: The number of circulating endothelial progenitor cells (EPCs) predicts future development of atherosclerotic cardiovascular disease (ASCVD) and is reduced in patients with type 2 diabetes (T2DM) or impaired glucose tolerance (IGT). Recent studies revealed the contribution of tight control of glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), as well as fatty acid oxidation in the regulation of stem cell behavior. In this study, we show that how dysregulated glucose and triglyceride metabolism in T2DM/IGT affects the homeostasis of EPCs, i.e. bone marrow stem/progenitor cells (BMSCs). In our clinical study, consistent with previous reports, the patients with IGT or T2DM showed reduced level of circulating EPCs, as compared normal glucose tolerance. On the other hand, fasting or postprandial hypertriglyceridemia (hTG) itself did not affect the level of circulating EPCs. However, further analysis using single and multiple regression analyses strongly suggested that, in the presence of postprandial hTG, postprandial hyperglycemia exerts devastating effect on EPC homeostasis. We therefore carried out the proof of concept study in mice. Our experimental study revealed that repetitive glucose+lipid (G+L) spikes, but not repetitive glucose (G) spikes or lipid (L) spikes, rapidly upregulated p53 in BMSCs and induced premature aging phenotype of bone marrow cells, i.e. the impairment of BMSC quiescence and function, and myeloid-biased differentiation. Subsequent analysis implicated that p53-mediated augmentation of mitochondrial OXPHOS plays pivotal role for the impairment of BMSC quiescence and function. On the other hand, it is still not clear how repetitive G+L injection induced myeloid-biased differentiation. Because cell-fate decisions are executed by transcription factors in response to extracellular signals, and the best-known function of p53 is as a transcription factor, we asked to what extent repetitive glucose spikes and repetitive glucose+TG spikes affect transcriptional regulation in LSK cells.

GEO Accession ID: GSE125682

PMID: 34533398

Visualize Samples

Info Visualizations are precomputed using the Python package scanpy on the top 5000 most variable genes.

Precomputed Differential Gene Expression

Info Differential expression signatures are automatically computed using the limma R package. More options for differential expression are available to compute below.

Signatures:

Select conditions:

Control Condition

Perturbation Condition

Only conditions with at least 1 replicate are available to select

Differential Gene Expression Analysis
Info Differential expression signatures can be computed using DESeq2 or characteristic direction.
Select differential expression analysis method:
Bulk RNA-seq Appyter

This pipeline enables you to analyze and visualize your bulk RNA sequencing datasets with an array of downstream analysis and visualization tools. The pipeline includes: PCA analysis, Clustergrammer interactive heatmap, library size analysis, differential gene expression analysis, enrichment analysis, and L1000 small molecule search.