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: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:Single cell sequencing of de-differentiated dermal adipocytes
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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
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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: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:Thymidylate synthase maintains the de-differentiated state of triple negative breast cancers
| PRJNA506989 | ENA
Project description:Obesity is a known risk factor for breast cancer. To identify genes and underlying pathways in human breast cancer cells affected by interaction with mature adipocytes, two estrogen-receptor positive (ER+) breast cancer cell lines, MCF-7 and T47D, and the triple-negative (TN) breast cancer cell line MDA-MB-231 were cultivated in a co-culture system with or without differentiated murine 3T3-L1 adipocytes for the purpose of a microarray gene expression analysis. The use of in vitro differentiated 3T3-L1 adipocytes allowed comparable experimental conditions for each of the co-culture experiments with human breast cancer cell lines. For co-cultivation analyses of 3T3-L1 and breast cancer cells, we set up a two-dimensional transwell system, which enables intercellular communication through soluble factors secreted into the medium but inhibits intermixture of the different cell types. Following 5 days of co-culture with or without differentiated adipocytes, total RNA was isolated from the human breast cancer cells and subjected to microarray gene expression analyses.
2018-06-22 | E-MTAB-6855 | biostudies-arrayexpress