Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell screens identify ADAM12 as a fibroblast checkpoint impeding anti-tumor immunity - scRNA-seq of murine KPC models

ABSTRACT: Clinical trials targeting cancer-associated fibroblasts (CAFs)—crucial pro-tumoral factors in cancer—have almost all failed. This may be ascribed to their intrinsic functional plasticity and the opaque regulatory circuits underlying their heterogeneous phenotypes within tumors. We address these by developing a systematic screening approach for patient-derived fibroblasts using complementary CRISPR interference (CRISPRi) and activation (CRISPRa)-based Perturb-seq . An anti-tumoral interferon (IFN)-I response-associated program is identified as the primary antagonism axis counteracting TGFβ-driven pro-tumoral myofibroblast activation. ADAM12 emerges as a molecular checkpoint mediating this relationship. Its ablation elicits IFN-I responsive programs, reconfigures myofibroblast population structures into progenitor-like states, revitalizes T cell-based immune responses, and induces tumor rejection across various murine models. Further combined with human genomics data analysis, our findings position ADAM12 as a potential target for fibroblasts, paving the way for actionable therapeutic interventions.

ORGANISM(S): Mus musculus

PROVIDER: GSE278983 | GEO | 2025/12/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Single-cell screens identify ADAM12 as a fibroblast checkpoint impeding anti-tumor immunity - RNA-seq of C57BL/6 murine models

Project description:Clinical trials targeting cancer-associated fibroblasts (CAFs)—crucial pro-tumoral factors in cancer—have almost all failed. This may be ascribed to their intrinsic functional plasticity and the opaque regulatory circuits underlying their heterogeneous phenotypes within tumors. We address these by developing a systematic screening approach for patient-derived fibroblasts using complementary CRISPR interference (CRISPRi) and activation (CRISPRa)-based Perturb-seq . An anti-tumoral interferon (IFN)-I response-associated program is identified as the primary antagonism axis counteracting TGFβ-driven pro-tumoral myofibroblast activation. ADAM12 emerges as a molecular checkpoint mediating this relationship. Its ablation elicits IFN-I responsive programs, reconfigures myofibroblast population structures into progenitor-like states, revitalizes T cell-based immune responses, and induces tumor rejection across various murine models. Further combined with human genomics data analysis, our findings position ADAM12 as a potential target for fibroblasts, paving the way for actionable therapeutic interventions.

2025-12-16 | GSE278980 | GEO

Single-cell screens identify ADAM12 as a fibroblast checkpoint impeding anti-tumor immunity - scRNA-seq of co-injection murine models

2025-12-16 | GSE278975 | GEO

Single-cell screens identify ADAM12 as a fibroblast checkpoint impeding anti-tumor immunity - scRNA-seq of Adam12CKO Mouse Model CD45- cells

Project description:Clinical trials targeting cancer-associated fibroblasts (CAFs)—crucial pro-tumoral factors in cancer—have almost all failed. This may be ascribed to their intrinsic functional plasticity and the opaque regulatory circuits underlying their heterogeneous phenotypes within tumors. We address these by developing a systematic screening approach for patient-derived fibroblasts using complementary CRISPR interference (CRISPRi) and activation (CRISPRa)-based perturb-seq. An anti-tumoral interferon (IFN)-I response-associated program is identified as the primary antagonism axis counteracting TGFβ-driven pro-tumoral myofibroblast activation. ADAM12 emerges as a molecular checkpoint mediating this relationship. Its ablation elicits IFN-I responsive programs, reconfigures myofibroblast population structures into progenitor-like states, revitalizes T cell-based immune responses, and induces tumor rejection across various murine models. Further combined with human genomics data analysis, our findings position ADAM12 as a potential target for fibroblasts, paving the way for actionable therapeutic interventions.

2025-12-16 | GSE313761 | GEO

Single-cell screens identify ADAM12 as a fibroblast checkpoint impeding anti-tumor immunity - RNA-seq of B16F10 lung melanoma murine models

2025-12-16 | GSE278974 | GEO

Molecular profiling of ADAM12+ MSCs in B16-OVA melanomas

Project description:This study investigates the transcriptome of ADAM12+ mesenchymal stromal cells (MSCs) in B16-OVA (MO5) melanomas

2023-10-05 | GSE206795 | GEO

Gene expression analysis in heart from wild-type or ADAM12 knockout mice under heart failure condition.

Project description:To investigated global changes caused by pressure overload-induced heart failure in ADAM12 knockout mice using a microarray analysis. A disintegrin and metalloproteinase (ADAM) 12 is has long been considered to promote cardiac dysfunction based on according to the finding report that a small molecule ADAM12 inhibitor, KB-R7785 ameliorated cardiac function in a transverse aortic constriction (TAC) model by inhibiting the through inhibition of proteolytic activation of HB-EGF signaling. HoweverOn the other hand, this compound has poor selectivity for ADAM12, and the role of ADAM12 inon cardiac dysfunction has not yet been investigated usingby genetic loss-of-function mice. Anoperation. ADAM12 deficiency resulted in significantly more expanded cardiac fibrosis accompanied byaccompanying with increased collagen-related gene expression in their failing hearts. The results of a genome-wide transcriptional analysis suggested a strongly enhanced highly elevated focal adhesion- and fibrosis-related signaling pathway in ADAM12 knockout hearts. The present results study revealed that the loss of ADAM12 enhanced focal adhesion and canonical TGF-β signaling by regulating the abundance of the integrin β1 and TGF-β receptors.

2019-10-18 | GSE137442 | GEO

Adam12 and lnc015192 act as ceRNAs in breast cancer by regulating miR-34a

Project description:Long non-coding RNAs (lncRNAs) are involved in the pathology of various tumors. However, the role of lncRNA in breast cancer remains unclear. We performed microarrays to identify the differentially expressed mRNAs and lncRNAs in breast tissues with or without miR-34a knockout. In vitro and in vivo assays were preformed to explore the biological effects of the differentially expressed mRNA and lncRNA in breast cancer cells. We found that Adam12 and lnc015192 were significantly upregulated in miR-34a knockout breast tissues. Knockdown of Adam12 and lnc015192 inhibited breast cancer cells migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Further study indicated that lnc015192 acted as a competing endogenous RNA (ceRNA) for miR-34a to regulate Adam12 expression. Taken together, our findings demonstrate how Adam12 and lnc015192 induce breast cancer metastasis and offer novel therapeutic targets for breast cancer.

2018-08-01 | GSE111587 | GEO

Depletion of ADAM12+ MSCs normalizes the tumor stromal microenvironment

Project description:This study investigates transcriptomic changes occurring in PDPN+PDGFRa+ stromal cells from murine B16-OVA melanomas (MO5) when ADAM12+ mesenchymal stromal cells (MSCs) are depleted.

2023-10-05 | GSE206794 | GEO

Single-cell screens identify ADAM12 as a fibroblast checkpoint impeding anti-tumor immunity

Project description:Single-cell screens identify ADAM12 as a fibroblast checkpoint impeding anti-tumor immunity

| PRJNA1169870 | ENA

Gene expression analysis of murine normal mammary gland fibroblasts (mNFs) after perturbing the expression of ASPA (silencing and over-expression)

Project description:Metabolic reprogramming is a hallmark of cancer, and the field has predominantly focused on investigating metabolic alterations in tumour cells. However, the relevance, mechanism and consequences of metabolic adaptations in stromal cells remains largely unexplored. Here, we identify Aspartoacylase (ASPA) as a metabolic enzyme consistently repressed in tumour stroma and cancer-associated fibroblasts (CAFs). Loss of ASPA is associated with the accumulation of its substrate, N-acetylaspartate (NAA), and we corroborate the relevance of this metabolite in the control of macrophage polarization. Importantly, we report an unprecedented reciprocal crosstalk of ASPA with TGFβ signalling. TGFβ suppresses ASPA expression, whereas ASPA restrains TGFβ-dependent myofibroblast conversion and the generation of aggressive pro-tumoral responses in fibroblasts. Analyses of human specimens revealed a strong negative prognostic value for ASPA in different tumour types, associated with pro-tumoral macrophages and TGFβ signalling levels. Our findings unveil ASPA expression in fibroblasts as a previously unknown gatekeeper of TGFβ responses and activation in cancer, and shed light into the intratumoral metabolic crosstalk that governs the process of cancer progression.

2025-12-10 | GSE304425 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data