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Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [RNA-seq]

ABSTRACT: Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [RNA-seq]

PROVIDER: PRJNA1232029 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32574875_1.fastq.gz	Fastqsanger.gz
	SRR32574875_2.fastq.gz	Fastqsanger.gz
	SRR32574876_1.fastq.gz	Fastqsanger.gz
	SRR32574876_2.fastq.gz	Fastqsanger.gz
	SRR32574877_1.fastq.gz	Fastqsanger.gz

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Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer

Project description:Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer

| PRJNA1232025 | ENA

Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [scRNA-seq]

Project description:Pancreatic ductal adenocarcinoma (PDAC) tumors are deficient in glutamine, an amino acid that tumor cells and cancer-associated fibroblasts (CAFs) use to sustain their fitness. In PDAC, both cell types stimulate macropinocytosis as an adaptive response to glutamine depletion. CAFs play a critical role in sculpting the tumor microenvironment, yet how adaptations to metabolic stress impact the stromal architecture remains elusive. In this study, we find that macropinocytosis functions to control CAF subtype identity when glutamine is limiting. Our data demonstrate that metabolic stress leads to an intrinsic inflammatory CAF (iCAF) program driven by MEK/ERK signaling. Utilizing in vivo models, we find that blocking macropinocytosis triggers CAF subtype transitions and reorganizes the tumor stroma. Importantly, these changes in stromal architecture can be exploited to sensitize PDAC to immunotherapy and chemotherapy. Our findings demonstrate that metabolic stress plays a role in shaping the tumor microenvironment, and that this attribute can be harnessed for therapeutic impact.

2025-05-16 | GSE291120 | GEO

Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [RNA-seq]

2025-05-16 | GSE291118 | GEO

Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [nanoString nCounter]

Project description:Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [nanoString nCounter]

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Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [scRNA-seq]

Project description:Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [scRNA-seq]

| PRJNA1232032 | ENA

Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [nanoString nCounter]

Project description:Pancreatic ductal adenocarcinoma (PDAC) tumors are glutamine-deficient, and both tumor cells and cancer-associated fibroblasts (CAFs) rely on this amino acid to maintain fitness and induce macropinocytosis as an adaptive response. CAFs play a critical role in sculpting the tumor microenvironment, yet how adaptations to metabolic stress impact the stromal architecture remains elusive. In this study, we find that macropinocytosis sustains the myCAF phenotype under glutamine limitation by preventing inflammatory reprogramming. Our data demonstrate that metabolic stress induces an intrinsic inflammatory CAF (iCAF) program through MEK-ERK signaling. We find that blocking macropinocytosis in vivo promotes myCAF-to-iCAF transitions, remodeling the tumor stroma. Importantly, stromal remodeling driven by macropinocytosis inhibition—including iCAF enrichment, collagen reduction, immune cell infiltration, and vascular expansion—sensitizes PDAC tumors to immunotherapy and chemotherapy. Our findings reveal that inhibiting macropinocytosis promotes an inflammatory, less fibrotic tumor microenvironment that can be leveraged to improve therapeutic responses in PDAC.

2025-06-27 | GSE301021 | GEO

Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-05-16 | GSE291121 | GEO

Macropinocytosis controls metabolic stress-driven CAF subtype identity in pancreatic cancer.

Project description:Pancreatic ductal adenocarcinoma (PDAC) tumors are deficient in glutamine, an amino acid that tumor cells and CAFs use to sustain their fitness. In PDAC, both cell types stimulate macropinocytosis as an adaptive response to glutamine depletion. CAFs play a critical role in sculpting the tumor microenvironment, yet how adaptations to metabolic stress impact the stromal architecture remains elusive. In this study, we find that macropinocytosis functions to control CAF subtype identity when glutamine is limiting. Our data demonstrate that metabolic stress leads to an intrinsic inflammatory CAF (iCAF) program driven by MEK/ERK signaling. Utilizing in vivo models, we find that blocking macropinocytosis alters CAF subtypes and reorganizes the tumor stroma. Importantly, these changes in stromal architecture can be exploited to sensitize PDAC to immunotherapy and chemotherapy. Our findings demonstrate that metabolic stress plays a role in shaping the tumor microenvironment, and that this attribute can be harnessed for therapeutic impact.

| S-EPMC11642790 | biostudies-literature

CAF-1 safeguards somatic cell identity during factor-induced reprogramming

Project description:Cellular differentiation involves profound changes in the chromatic landscape, yet the mechanisms by which somatic cell identity is subsequently maintained remain incompletely understood. To further elucidate regulatory pathways that safeguard the somatic state, we performed two comprehensive RNAi screens targeting chromatin factors during transcription factor-mediated reprogramming of mouse fibroblasts to induced pluripotent stem cells (iPSCs). Remarkably, subunits of the chromatin assembly factor-1 (CAF-1) complex emerged as the most prominent hits from both screens, followed by modulators of lysine sumoylation and heterochromatin maintenance. Suppression of CAF-1 increased reprogramming efficiency by several orders of magnitude and facilitated iPSC formation in as little as 4 days. Mechanistically, CAF-1 suppression led to a more accessible chromatin structure at enhancer elements early during reprogramming. These changes were accompanied by a decrease in somatic heterochromatin domains, increased binding of Sox2 to pluripotency-specific targets and activation of associated genes. Notably, suppression of CAF-1 also enhanced the direct conversion of B cells into macrophages and fibroblasts into neurons. Together, our findings reveal the histone chaperone CAF-1 as a novel regulator of somatic cell identity during transcription factor-induced cell fate transitions and provide a potential strategy to modulate cellular plasticity in a regenerative setting. Gene expression analysis in CAF-1 knockdown and Renilla control during early OKSM-induced reprogramming by microarray

2015-12-10 | E-GEOD-72741 | biostudies-arrayexpress

The histone chaperone CAF-1 safeguards somatic cell identity during transcription factor-induced reprogramming (sequencing)

Project description:During development, specialized cell lineages are generated through the establishment of cell type-specific transcriptional patterns and epigenetic programs. However, the precise mechanisms and regulators that maintain these specialized cell states remain largely elusive. To identify molecules that safeguard somatic cell identity, we performed two comprehensive RNAi screens targeting known and predicted chromatin regulators during transcription factor-mediated reprogramming of mouse fibroblasts to induced pluripotent stem cells (iPSCs). Remarkably, subunits of the chromatin assembly factor-1 (CAF-1) complex emerged as the most prominent hits from both screens, followed by modulators of lysine sumoylation, DNA methylation and heterochromatin maintenance. Suppression of CAF-1 increased reprogramming efficiencies by several orders of magnitude and generated iPSCs two to three times faster compared to controls without affecting cell proliferation. We demonstrate that suppression of CAF-1 leads to a more accessible chromatin structure specifically at enhancer elements early during reprogramming. These changes were accompanied by increased binding of the reprogramming factor Sox2 to ESC-specific regulatory elements and earlier activation of pluripotency-associated genes. Notably, suppression of CAF-1 also enhanced iPSC formation from blood progenitors as well as the direct conversion of B cells into macrophages and fibroblasts into neurons. Together, our findings reveal the histone chaperone CAF-1 as an unanticipated regulator of somatic cell identity and provide a potential strategy to modulate cellular plasticity in a regenerative setting. Keywords: Genome binding/occupancy profiling by high throughput sequencing Chromatin accessibility and Sox2 bindings in CAF-1 knockdown and Renilla control during early OKSM reprogramming by high throughput sequencing

2015-12-10 | E-GEOD-72744 | biostudies-arrayexpress

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