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Physiologic media renders human iPSC-derived macrophages permissive for M. tuberculosis by rewiring organelle function and metabolism

ABSTRACT: Physiologic media renders human iPSC-derived macrophages permissive for M. tuberculosis by rewiring organelle function and metabolism

PROVIDER: PRJNA1075086 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27928500_1.fastq.gz	Fastqsanger.gz
	SRR27928500_2.fastq.gz	Fastqsanger.gz
	SRR27928501_1.fastq.gz	Fastqsanger.gz
	SRR27928501_2.fastq.gz	Fastqsanger.gz
	SRR27928502_1.fastq.gz	Fastqsanger.gz

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Physiologic media renders human iPSC-derived macrophages permissive for M. tuberculosis by rewiring organelle function and metabolism

Project description:In vitro studies are crucial for our understanding of the human macrophage immune functions. However, traditional in vitro culture media poorly reflect the metabolic composition of blood, potentially affecting the outcomes of these studies. Here, we analysed the impact of a physiological medium on human induced pluripotent stem cell (iPSC)-derived macrophages (iPSDM) function. Macrophages cultured in a human plasma-like medium (HPLM) were more permissive to Mycobacterium tuberculosis (Mtb) replication and showed decreased lipid metabolism with increased metabolic polarisation. Functionally, HPLM-differentiated macrophages showed different metabolic organelle content and activity. Specifically, HPLM-cultured macrophages displayed reduced lipid droplet and peroxisome content, increased lysosomal proteolytic activity, and increased mitochondrial activity and dynamics. Inhibiting or inducing lipid droplet formation revealed that lipid droplet content is a key factor influencing macrophage permissiveness to Mtb. These findings underscore the importance of using physiologically relevant media in vitro for accurately studying human macrophage function.

2024-06-28 | GSE255475 | GEO

Inhaled TLR9 Agonist Renders Lung Tumors Permissive to PD-1 Blockade Promoting Optimal CD4+ and CD8+ T cell Interplay

Project description:Inhaled TLR9 Agonist Renders Lung Tumors Permissive to PD-1 Blockade Promoting Optimal CD4+ and CD8+ T cell Interplay

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A cooperative organelle biogenesis program in mammalian cells

Project description:The compartmentalisation of distinct organelles within eukaryotic cells is essential for their diverse functions, however, how their structures and functions depend on each other has not been systematically explored. We combined a fluorescent reporter of mitochondrial stress with genome-wide CRISPR knockout screening and identified networks of genes involved in the biogenesis and metabolism of diverse organelles. Targeted organelle gene knockouts identified that defects in peroxisomes, Golgi, and ER cause mitochondrial fragmentation and dysfunction. Correlative light and electron microscopy analysed using artificial intelligence-directed voxel extraction revealed in unprecedented detail how impaired mitochondrial interactions with diverse organelles caused cell-wide defects in their morphology and biogenesis. Multi-omics analyses identified a unified proteome stress response and global shifts in lipid and glycoprotein homeostasis that are elicited when organelle biogenesis is compromised. Our comprehensive resource has defined metabolic and morphological interactions between organelles that can be mined to understand how changes in organelle components drive diverse cellular pathologies.

2023-10-13 | GSE201573 | GEO

Functional multi-organelle units control inflammatory lipid metabolism of macrophages

Project description:Eukaryotic cells contain several membrane-separated organelles to compartmentalize distinct metabolic reactions. However, it has remained unclear how these organelle systems are coordinated, when cells adapt metabolic pathways to support their development, survival or effector functions. Here we present OrgaPlexing, a multispectral organelle imaging approach for the comprehensive mapping of six key metabolic organelles and their interactions. We use this analysis on macrophages, immune cells that undergo rapid metabolic switches upon sensing bacterial and inflammatory stimuli. Our results identify lipid droplets (LDs) as primary inflammatory responder organelle, which forms three- and four-way interactions with other organelles. While clusters with endoplasmic reticulum (ER) and mitochondria (M-ER-LD unit) help supply fatty acids for LD growth, the additional recruitment of peroxisomes (M-ER-P-LD unit) supports fatty acid efflux from LDs. Interference with individual components of these units has direct functional consequences for inflammatory lipid synthesis. Together, we show that macrophages form functional multi-organellar units (MOUs) to support metabolic adaptation, and provide an experimental strategy to identify organelle-metabolic signaling hubs.

2024-05-03 | GSE235484 | GEO

Global rewiring of cellular metabolism renders Saccharomyces cerevisiae Crabtree negative.

Project description:Saccharomyces cerevisiae is a Crabtree-positive eukaryal model organism. It is believed that the Crabtree effect has evolved as a competition mechanism by allowing for rapid growth and production of ethanol at aerobic glucose excess conditions. This inherent property of yeast metabolism and the multiple mechanisms underlying it require a global rewiring of the entire metabolic network to abolish the Crabtree effect. Through rational engineering of pyruvate metabolism combined with adaptive laboratory evolution (ALE), we demonstrate that it is possible to obtain such a global rewiring and hereby turn S. cerevisiae into a Crabtree-negative yeast. Using integrated systems biology analysis, we identify that the global rewiring of cellular metabolism is accomplished through a mutation in the RNA polymerase II mediator complex, which is also observed in cancer cells expressing the Warburg effect.

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Host Factors with Reduced Expression in Two HCV Permissive Cell Lines as Compared to the Non-Permissive Parent Cell Line Huh7

Project description:Drugs directly targeting Hepatitis C (HCV) are often rendered useless by the high mutation rate of the virus. Thus, we deduce that targeting of host factor that affect HCV replication may provide enhanced therapy fort HCV infection. Hepatocyte cell line Huh7 is known to be non-permissive for Hepatits C (HCV) replication. Through a method developed by the Rice laboratory (Blight, K.J., et al., J Virol, 2002), selection of a small subset of permissive hepatocytes is possible. The Rice laboratory generated the first permissive cell line, Huh7.5, using this method. We generated another permissive cell line, HRP1, using the same method. With microarray, we compared the expression of host mRNAs in non-permissive Huh7 to both Huh7.5 and HRP1 searching for host factors lost in the cell lines permisive for HCV replication. Non-permissive cell line Huh7 and permissive cell lines Huh7.5 and HRP1 were harvested for RNA extraction and hybridization on Affymetrix microarrays.

2011-05-01 | E-GEOD-25156 | biostudies-arrayexpress

Organelle genome of Ulvaceae species

Project description:Organelle genome of Ulvaceae species Raw sequence reads

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Single-cell RNA-sequencing of breast cancer cells growing in invasion permissive and non-permissive 3D matrices

Project description:Murine breast cancer organoids (MMTV-PyMT) were embeded in basement membrane extract (BME, invasion non-permissive) or collagen I (invasion-permissive). Organoids were harvested after 5days for single-cell RNA-sequencing (SORT-seq).

2022-12-13 | GSE197821 | GEO

Host Factors with Reduced Expression in Two HCV Permissive Cell Lines as Compared to the Non-Permissive Parent Cell Line Huh7

2011-05-01 | GSE25156 | GEO

Medicago truncatula R108: permissive medium versus non permissive medium. Comparison of the transcriptomic response of medicago truncatula plants.

Project description:12plex_medicago_2013-08 - r108 permissive medium versus non permissive medium. - Two experiments to compare the transcriptomic response of medicago plants: Agar medium versus Phytagel medium (exp1) and rhizobium WT versus BacA (exp2). - Medicago truncatula R108 seedlings were inoculated with S. medicae WSM419 and were cultivated during three days on buffered nidulation medium solidified with Phytagel or Agar.

2018-11-01 | GSE121771 | GEO

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