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Single-cell multiome uncovers differences in glycogen metabolism underlying species-specific speed of development

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Macaca fascicularis Homo sapiens

PROVIDER: GSE275572 | GEO | 2024/09/05

REPOSITORIES: GEO

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Single-cell multiome uncovers differences in glycogen metabolism underlying species-specific speed of development [mTORi]

Project description:Embryos from different mammalian species develop at characteristic timescales. These timescales are recapitulated during the differentiation of pluripotent stem cells in vitro. Specific genes and molecular pathways that modulate cell differentiation speed between mammalian species remain to be identified. Here we use single-cell multi-omic analysis of neural differentiation of mouse, cynomolgus monkey and human pluripotent cells to identify new regulators for differentiation speed. We demonstrate that species-specific differences in transcriptome dynamics are mirrored at the chromatin level, but that, contrary to other developmental contexts, the speed of neural differentiation is insensitive to manipulations of cell growth and cycling. Exploiting the single-cell resolution of our data, we identify glycogen storage levels regulated by UGP2 expression as a new species-specific trait of pluripotent cells, and show that lowered glycogen storage in UGP2 mutant cells is associated with accelerated neural differentiation. The control of energy storage could be a general strategy for the regulation of cell differentiation speed.

2024-09-05 | GSE275571 | GEO

Single-cell multiome uncovers differences in glycogen metabolism underlying species-specific speed of development [UGP2 KO]

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Single-cell multiome uncovers differences in glycogen metabolism underlying species-specific speed of development [scRNAseq and scATACseq]

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Single-cell multiome uncovers differences in glycogen metabolism underlying species-specific speed of development

Project description:Single-cell multiome uncovers differences in glycogen metabolism underlying species-specific speed of development

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Single-cell multiome uncovers differences in glycogen metabolism underlying species-specific speed of development [mTORi]

Project description:Single-cell multiome uncovers differences in glycogen metabolism underlying species-specific speed of development [mTORi]

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Single-cell multiome uncovers differences in glycogen metabolism underlying species-specific speed of development [UGP2 KO]

Project description:Single-cell multiome uncovers differences in glycogen metabolism underlying species-specific speed of development [UGP2 KO]

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Single-cell multiome uncovers differences in glycogen metabolism underlying species-specific speed of development [scRNAseq and scATACseq]

Project description:Single-cell multiome uncovers differences in glycogen metabolism underlying species-specific speed of development [scRNAseq and scATACseq]

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Mitochondria Metabolism Sets the Species-Specific Tempo of Neuronal Development

Project description:Neuronal development in the human cerebral cortex is considerably prolonged compared to that of other mammals. We explored whether mitochondria influence the species-specific timing of cortical neuron maturation. By comparing human and mouse cortical neuronal maturation at high temporal and cell resolution, we found a slower mitochondria development in human cortical neurons compared with that in the mouse, together with lower mitochondria metabolic activity, particularly that of oxidative phosphorylation. Stimulation of mitochondria metabolism in human neurons resulted in accelerated development in vitro and in vivo, leading to maturation of cells weeks ahead of time, whereas its inhibition in mouse neurons led to decreased rates of maturation. Mitochondria are thus important regulators of the pace of neuronal development underlying human-specific brain neoteny.

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Glycogen metabolism and glycogen storage disorders.

Project description:Glucose is the main energy fuel for the human brain. Maintenance of glucose homeostasis is therefore, crucial to meet cellular energy demands in both - normal physiological states and during stress or increased demands. Glucose is stored as glycogen primarily in the liver and skeletal muscle with a small amount stored in the brain. Liver glycogen primarily maintains blood glucose levels, while skeletal muscle glycogen is utilized during high-intensity exertion, and brain glycogen is an emergency cerebral energy source. Glycogen and glucose transform into one another through glycogen synthesis and degradation pathways. Thus, enzymatic defects along these pathways are associated with altered glucose metabolism and breakdown leading to hypoglycemia ± hepatomegaly and or liver disease in hepatic forms of glycogen storage disorder (GSD) and skeletal ± cardiac myopathy, depending on the site of the enzyme defects. Overall, defects in glycogen metabolism mainly present as GSDs and are a heterogenous group of inborn errors of carbohydrate metabolism. In this article we review the genetics, epidemiology, clinical and metabolic findings of various types of GSD, and glycolysis defects emphasizing current treatment and implications for future directions.

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Species-specific pace of development is associated with differences in protein stability.

Project description:Although many molecular mechanisms controlling developmental processes are evolutionarily conserved, the speed at which the embryo develops can vary substantially between species. For example, the same genetic program, comprising sequential changes in transcriptional states, governs the differentiation of motor neurons in mouse and human, but the tempo at which it operates differs between species. Using in vitro directed differentiation of embryonic stem cells to motor neurons, we show that the program runs more than twice as fast in mouse as in human. This is not due to differences in signaling, nor the genomic sequence of genes or their regulatory elements. Instead, there is an approximately two-fold increase in protein stability and cell cycle duration in human cells compared with mouse cells. This can account for the slower pace of human development and suggests that differences in protein turnover play a role in interspecies differences in developmental tempo.

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