Single cell sequencing of de-differentiated adipocytes induced by breast tumor
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ABSTRACT:
PROVIDER: PRJNA625271 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: The goals of this study are to determine adipocyte de-differentiation and the fate of these de-differentiated cells in breast tumor. Methods: Library prepared followed by 10X Genomics standard protocol. Transcriptome was generated by high throughput sequencing.
2022-09-02 | GSE148646 | GEO
Project description:Single cell sequencing of de-differentiated dermal adipocytes
| PRJNA531057 | ENA
Project description:Adipose tissue in the mammary gland undergoes dramatic remodeling during reproduction. Adipocytes are replaced by mammary alveolar structures during pregnancy and lactation, then reappear upon weaning. Here, we reveal that adipocytes in the mammary gland de-differentiate into Pdgfrα+ preadipocyte- and fibroblast-like cells during pregnancy, and remain de-differentiated during lactation. Upon weaning, de-differentiated fibroblasts proliferate and re-differentiate into adipocytes. In order to determine the molecular signature of these de-differentiated adipocytes in the mammary gland, we compared these cells with classical adipocytes. Using the AdipoChaser-mT/mG system, we pre-labeled mature adipocytes with GFP expression to characterize the features of these de-differentiated adipocytes (Figure 4A), and then purified CD31-/CD45-/PDGFRα+/Tomato+ and CD31-/CD45-/PDGFRα+/GFP+ cells from the stromal vascular fraction (SVF) of lactating mammary gland at the peak of lactation through FACS. Gene expression analyses showed that the CD31-/CD45-/PDGFRα+/Tomato+ cells were indeed enriched with Tomato expression, while the CD31-/CD45-/PDGFRα+/GFP+ cells were enriched with GFP expression (Figure 4C). We then collected CD31-/CD45-/PDGFRα+/GFP+ cells as single cells for subsequent single cell RNA-sequencing analysis (Figure 4D-G, Supplemental. Figure S1A-G). After the flow sorting and single cell RNA amplification, 26 CD31-/CD45-/PDGFRα+/GFP+ cells passed the quality control, and these cells were used for single-cell RNA-sequencing analysis. Due to technical difficulties in sorting single mature white adipocyte through flow cytometry, adipocytes differentiated from the immortalized murine-derived brown pre-adipocyte cell line were used as mature adipocyte control (Pradhan et al., 2017). Additionally, we also included population RNA-seq experiments, i.e. three mature white adipocyte samples, two GFP+, and six GFP- ones.
2018-06-17 | E-MTAB-6818 | biostudies-arrayexpress
Project description:Purpose: The goals of this study are to compare the de-differentiated dermal adipocytes with normal skin fibroblasts. Methods: Library prepared followed by 10X Genomics standard protocol. Transcriptome was generated by high throughput sequencing.
2019-09-16 | GSE129371 | GEO
Project description:Single-cell RNA-seq of de-differentiated mammary adipocytes during lactation
| PRJEB27175 | ENA
Project description:Cancer development and progression depend on tumor cell intrinsic factors, the tumor microenvironment and host characteristics. Despite the identification of the plasticity of adipocytes, the primary breast stromal cells, both in physiology and cancer, we lack a complete understanding of mechanisms that regulate adipocyte-tumor cell crosstalk. Here we dissected the breast cancer crosstalk with adipocytes and studied relevant molecules. We identified that the ability of breast cancer cells to dedifferentiate adipocytes is intrinsic subtype-dependent, with all breast cancer subtypes, except for HER2+ER+ subtype, capable of inducing this phenomenon. Crosstalk between breast cancer cells and adipocytes in vitro increased cancer stem-like features and recruitment of pro-tumorigenic immune cells, through chemokine production. Serum amyloid A1 (SAA1) was in vitro identified as a regulator of the adipocyte dedifferentiation program in triple-negative breast cancer (TNBC) through CD36 and P2XR7 signaling. In human TNBCs, SAA1 expression was associated with CAA infiltration, inflammation, stimulated lipolysis, stem-like properties and distinct tumor immune microenvironment. Our findings provide evidence that interaction between tumor cells and adipocytes through SAA1 release is relevant to the aggressiveness of TNBC, potentially supporting its targeting.
2024-01-15 | PXD041186 | Pride
Project description:Analysis of gene expression levels of HER2-positive breast cancer cells exposed to the conditioned medium from adipocytes. The hypothesis tested in the present study was that adipocytes secrete factors that induce the resistance of cancer cells to antibody-dependent cellular cytotoxicity mediated by trastuzumab. The results provide insight into the genes that may be involved in the adipocyte-induced cancer resistance to trastuzumab treatment. BT474 cells or SKBR3 cells were exposed to the conditioned medium (CM) from differentiated hMADS (#hMADS) or to the control medium for 2 h. Total RNA was extracted and analyzed. The experiment was performed in triplicate.
2015-04-01 | E-GEOD-52660 | biostudies-arrayexpress
Project description:The progression of noninvasive ductal carcinoma in situ to invasive ductal carcinoma for patients with breast cancer results in a significantly poorer prognosis and is the precursor to metastatic disease. In this work, we have identified insulin-like growth factor–binding protein 2 (IGFBP2) as a potent adipocrine factor secreted by healthy breast adipocytes that acts as a barrier against invasive progression. In line with this role, adipocytes differentiated from patient-derived stromal cells were found to secrete IGFBP2, which significantly inhibited breast cancer invasion. This occurred through binding and sequestration of cancer-derived IGF-II. Moreover, depletion of IGF-II in invading cancer cells using small interfering RNAs or an IGF-II–neutralizing antibody ablated breast cancer invasion, highlighting the importance of IGF-II autocrine signaling for breast cancer invasive progression. Given the abundance of adipocytes in the healthy breast, this work exposes the important role they play in suppressing cancer progression and may help expound upon the link between increased mammary density and poorer prognosis.
2023-07-13 | PXD036479 | Pride
Project description:A high degree of cell plasticity seems to promote malignant tumour progression, and an epithelial-mesenchymal transition (EMT) is suspected to provide cancer cells with increased cell plasticity for the development of metastasis and therapy resistance. Here, we have tested whether the EMT-induced cancer cell plasticity can be therapeutically exploited and we report the efficient conversion of breast cancer cells, which have undergone an EMT, into post-mitotic adipocytes. Delineation of the molecular pathways underlying such transdifferentiation has motivated a combination therapy with a MEK inhibitor and Rosiglitazone to demonstrate the conversion of invasive cancer cells into adipocytes and the repression of primary tumor invasion and metastasis formation in mouse models of breast cancer. The results indicate the high potential to utilize the increased cell plasticity of invasive cancer cells for differentiation therapy and they raise the possibility to employ pharmacological treatments to interfere with tumor invasion and metastasis.
2019-01-23 | GSE89553 | GEO
Project description:Cancer cells frequently boost nucleotide metabolism (NM) to support their increased proliferation, but the consequences of elevated NM on tumor de-differentiation are mostly unexplored. Here, we identified a role for thymidylate synthase (TS), a NM enzyme and established drug target, in cancer cell de-differentiation and investigated its clinical significance in breast cancer (BC). In vitro, TS knockdown increased the population of CD24+ differentiated cells, and attenuated migration and sphere-formation. RNA-seq profiling indicated a repression of epithelial-to-mesenchymal transition (EMT) signature genes upon TS knockdown, and TS-deficient cells showed an increased ability to invade and metastasize in vivo, consistent with the occurrence of a partial EMT phenotype. Mechanistically, TS enzymatic activity was found essential for the maintenance of the EMT/stem-like state by fueling a dihydropyrimidine dehydrogenase – dependent pyrimidine catabolism. In patient tissues, TS levels were found significantly higher in poorly differentiated and in triple negative BC, and strongly correlated with worse prognosis. The present study provides the rationale to study in-depth the role of NM at the crossroads of proliferation and differentiation, and depicts new avenues for the design of novel drug combinations for the treatment of BC
2019-02-01 | GSE122953 | GEO