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Identification of a CD106+ pericyte stem cell leading to Ly6G+ cell accumulation responsible for resistance to immunotherapy in pancreatic cancer

ABSTRACT: Identification of a CD106+ pericyte stem cell leading to Ly6G+ cell accumulation responsible for resistance to immunotherapy in pancreatic cancer

PROVIDER: PRJNA911164 | ENA |

REPOSITORIES: ENA

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Identification of a CD106+ pericyte stem cell leading to Ly6G+ cell accumulation responsible for resistance to immunotherapy in pancreatic cancer

2023-01-20 | GSE220687 | GEO

Pericyte stem cells induce Ly6G+ cell accumulation and immunotherapy resistance in pancreatic cancer

Project description:We report the identification of a cell population that shares pericyte, stromal and stemness features, does not harbour the KrasG12D mutation and drives tumoral growth in vitro and in vivo. We term these cells pericyte stem cells (PeSCs) and define them as CD45-EPCAM-CD29+CD106+CD24+CD44+ cells. We perform studies with p48-Cre;KrasG12D (KC), pdx1-Cre;KrasG12D;Ink4a/Arffl/fl (KIC) and pdx1-Cre;KrasG12D;p53R172H (KPC) and tumor tissues from PDAC and chronic pancreatitis patients. We also perform single cell RNAseq analysis and reveal a unique signature of PeSC. Under steady-state conditions, PeSCs are barely detectable in the pancreas but present in the neoplastic microenvironment both in humans and mice. The co-injection of PeSCs and tumor epithelial cells leads to increased tumor growth, differentiation of Ly6G+ myeloid-derived suppressor cells and a decreased amount of F4/80+ macrophages and CD11c+ dendritic cells. This population induces resistance to anti-PD-1 immunotherapy when co-injected with epithelial tumor cells. Our data reveal the existence of a cell population that instructs immunosuppressive myeloid cell responses to bypass PD-1 targeting and thus suggest potential new approaches for overcoming resistance to immunotherapy in clinical settings.

| S-SCDT-10_15252-EMBR_202256524 | biostudies-other

Expression data from Ly6G+ and Ly6G- dendritic cells (DC)

Project description:To investigate the functional properties of Ly6G+ DC, we employed GeneChip analysis to compare the gene expression profiles between Ly6G+ DC and Ly6C- DC.

2013-02-01 | GSE28408 | GEO

Pericyte stem cells induce Ly6G<sup>+</sup> cell accumulation and immunotherapy resistance in pancreatic cancer.

Project description:We report the identification of a cell population that shares pericyte, stromal and stemness features, does not harbor the KrasG12D mutation and drives tumoral growth in vitro and in vivo. We term these cells pericyte stem cells (PeSCs) and define them as CD45- EPCAM- CD29+ CD106+ CD24+ CD44+ cells. We perform studies with p48-Cre;KrasG12D (KC), pdx1-Cre;KrasG12D ;Ink4a/Arffl/fl (KIC) and pdx1-Cre;KrasG12D ;p53R172H (KPC) and tumor tissues from PDAC and chronic pancreatitis patients. We also perform single-cell RNAseq analysis and reveal a unique signature of PeSC. Under steady-state conditions, PeSCs are barely detectable in the pancreas but present in the neoplastic microenvironment both in humans and mice. The coinjection of PeSCs and tumor epithelial cells leads to increased tumor growth, differentiation of Ly6G+ myeloid-derived suppressor cells, and a decreased amount of F4/80+ macrophages and CD11c+ dendritic cells. This population induces resistance to anti-PD-1 immunotherapy when coinjected with epithelial tumor cells. Our data reveal the existence of a cell population that instructs immunosuppressive myeloid cell responses to bypass PD-1 targeting and thus suggest potential new approaches for overcoming resistance to immunotherapy in clinical settings.

| S-EPMC10074138 | biostudies-literature

Expression data from Ly6G+ and Ly6G- dendritic cells (DC)

Project description:To investigate the functional properties of Ly6G+ DC, we employed GeneChip analysis to compare the gene expression profiles between Ly6G+ DC and Ly6C- DC. Crude bone marrow (BM) cells prepared from C57BL/6 mice were cultured in the presence of GM-CSF. On day 6, CD11c+/MHC II+/Ly6G+ cells and CD11c+/MHC II+/Ly6G- cells were simultaneously sorted from the same cultures by FACSAria. Total RNA were extracted and hybridized on Affymetrix microarrays.

2013-02-01 | E-GEOD-28408 | biostudies-arrayexpress

scRNAseq datasets supporting a common precursor expression program leading to brain pericyte differentiation from neural crest and mesoderm

Project description:Brain pericytes are critical for regulating endothelial barrier function and activity, thus ensuring adequate blood flow to the brain. How the developmental acquisition of pericytes to naked endothelium is regulated, is largely unknown, but is relevant to disorders where vessels are poorly stabilized. Although pericytes are derived from neural crest and mesoderm, brain pericytes from both origins are currently indistinguishable; the genetic pathways leading to a convergent pericyte phenotype are unknown. We show here that a precursor population expressing the transcription factor nkx3.1 with origins in both NCC and mesoderm, develops into brain pericytes. We identify the gene signature of these precursors and show that an nkx3.1, foxf2a, and cxcl12b -expressing pericyte precursor population is present around the cxcr4 expressing basilar artery, and that these cells later spread throughout the brain. Cxcl12b- Cxcr4 signaling is required for pericyte attachment and differentiation but not for later pericyte development. Further, both nkx3.1 and cxcl12b are necessary and sufficient in regulating pericyte number. Thus, we have defined an undescribed population of pericyte precursors and identified genes critical for their differentiation.

2024-02-25 | GSE232163 | GEO

Bulk RNA-Seq datasets supporting a common precursor expression program leading to brain pericyte differentiation from neural crest and mesoderm

2024-02-25 | GSE232762 | GEO

A common precursor expression program leading to brain pericyte differentiation from neural crest and mesoderm

Project description:Brain pericytes are one of the critical cell types that regulate endothelial barrier function and activity, thus ensuring adequate blood flow to the brain. The genetic pathways guiding undifferentiated cells into mature pericytes are not well understood. We show here that pericyte precursor populations from both neural crest and head mesoderm of zebrafish express the transcription factor nkx3.1 develop into brain pericytes. We identify the gene signature of these precursors and show that an nkx3.1-, foxf2a-, and cxcl12b-expressing pericyte precursor population is present around the basilar artery prior to artery formation and pericyte recruitment. The precursors later spread throughout the brain and differentiate to express canonical pericyte markers. Cxcl12b-Cxcr4 signaling is required for pericyte attachment and differentiation. Further, both nkx3.1 and cxcl12b are necessary and sufficient in regulating pericyte number as loss inhibits and gain increases pericyte number. Through genetic experiments, we have defined a precursor population for brain pericytes and identified genes critical for their differentiation. This SuperSeries is composed of the SubSeries listed below.

2024-02-25 | GSE232763 | GEO

A common precursor expression program leading to brain pericyte differentiation from neural crest and mesoderm

Project description:A common precursor expression program leading to brain pericyte differentiation from neural crest and mesoderm

| PRJNA973709 | ENA

Human tumor pericyte protein mass spectrometry

Project description:Proteomics analysis can reveal the differences of protein expression between mural cells (known as pericytes) from normal adjacent tissues (NPC) and tumors (TPC), implying the effectiveness of pericyte to tumor.

2021-08-24 | PXD026963 | Pride

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