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Single-cell RNA-seq Identifies Dynamic Cardiac Transition Program from Adipose Derived Cells Induced by Leukemia Inhibitory Factor

ABSTRACT: Single-cell RNA-seq Identifies Dynamic Cardiac Transition Program from Adipose Derived Cells Induced by Leukemia Inhibitory Factor

PROVIDER: PRJNA690563 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13380207_1.fastq.gz	Fastqsanger.gz
	SRR13380207_2.fastq.gz	Fastqsanger.gz
	SRR13380208_1.fastq.gz	Fastqsanger.gz
	SRR13380208_2.fastq.gz	Fastqsanger.gz
	SRR13380209_1.fastq.gz	Fastqsanger.gz

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Single-cell RNA-seq Identifies Dynamic Cardiac Transition Program from Adipose Derived Cells Induced by Leukemia Inhibitory Factor

Project description:Adipose-derived cells (ADCs) from white adipose tissue (WAT) are promising stem cell candidates due to large innate regenerative reserves and achievement of clinically meaningful cardiac regeneration. However, due to the heterogeneity of ADCs and unsolved molecular mechanism underpins of cardiac acquisition, the ADC-Cardiac transition efficiency remains low. Here, we found a population of ADCs reacted to leukemia inhibitory factor (LIF) and differentiated into functional beating cardiomyocyte-like cells. With single cells sequencing, we profiled 39,432 single cell transcriptomes at multiple time points throught the cardiac transition course. Combined with FACS, we identified three distinct pdgfra+ ADC populations that responded differently to the LIF signaling and transited to cardiomyocyte like cells. Dynamic trajectories derived from pseudotime analysis on ADCs navigate a trajectory with two branches that correspond to two alternative fate decisions. Analysis of starting branch revealed Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling is the crucial event in initiation of myogenic program. The ending two branches represented activated myofibroblast and cardiomyocyte like cells. Collectively, our findings offer a high-resolution dissection of ADC heterogeneity and cell fate dynamics during ADCs-Cardiac transition, thus shed new insights into potential cardiac stem cells for future usage.

2022-10-26 | GSE164410 | GEO

Single-Cell RNA-Seq Identifies Dynamic Cardiac Transition Program from ADCs Induced by Leukemia Inhibitory Factor.

Project description:Adipose-derived cells (ADCs) from white adipose tissue are promising stem cell candidates because of their large regenerative reserves and the potential for cardiac regeneration. However, given the heterogeneity of ADC and its unsolved mechanisms of cardiac acquisition, ADC-cardiac transition efficiency remains low. In this study, we explored the heterogeneity of ADCs and the cellular kinetics of 39,432 single-cell transcriptomes along the leukemia inhibitory factor (LIF)-induced ADC-cardiac transition. We identified distinct ADC subpopulations that reacted differentially to LIF when entering the cardiomyogenic program, further demonstrating that ADC-myogenesis is time-dependent and initiates from transient changes in nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. At later stages, pseudotime analysis of ADCs navigated a trajectory with 2 branches corresponding to activated myofibroblast or cardiomyocyte-like cells. Our findings offer a high-resolution dissection of ADC heterogeneity and cell fate during ADC-cardiac transition, thus providing new insights into potential cardiac stem cells.

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Dynamic patterns of DNA methylation in the normal prostate epithelial differentiation program are targets of aberrant methylation in prostate cancer

Project description:Understanding the epigenetic control of normal differentiation programs might yield principal information about critical regulatory states that are disturbed in cancer. We utilized the established non-malignant HPr1-AR prostate epithelial cell model that upon androgen exposure commits to a luminal cell differentiation trajectory from that of a basal-like state. We profile the dynamic transcriptome associated with this transition at multiple time points (0hr, 1hr, 24hr, 96hr), and confirm that expression patterns are strongly indicative of a progressive basal to luminal cell differentiation program based on human expression signatures. Furthermore, we establish dynamic patterns of DNA methylation associated with this program by use of whole genome bisulfite sequencing (WGBS).

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Dynamic patterns of DNA methylation in the normal prostate epithelial differentiation program are targets of aberrant methylation in prostate cancer [BiSulfite-seq]

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mTORC1 controls a dynamic program of TOP mRNA translation via LARP1

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Quiescent glioblastoma cells shift to an epithelial-mesenchymal transition-like gene program

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HOX13-dependent chromatin accessibility underlies the transition towards the digit development program

Project description:HOX13-dependent chromatin accessibility underlies the transition towards the digit development program

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A conserved differentiation program facilitates inhibitory neuron production in the developing mouse and human cerebellum

Project description:A conserved differentiation program facilitates inhibitory neuron production in the developing mouse and human cerebellum

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A specific lipid metabolic profile is associated with the epithelial mesenchymal transition program

Project description:Several studies have identified a specific metabolic program that is associated with the process of epithelial-mesenchymal transition (EMT). Whereas much is known about the association between glucose metabolism and EMT, the contribution of lipid metabolism is not still completely understood. Here, we studied epithelial and mesenchymal breast cancer cells by proteomic and lipidomic approaches and identified significant differences that characterised these models concerning specific metabolic enzymes and metabolites including fatty acids and phospholipids. Higher levels of monounsaturated fatty acids together with increased expression of enzymes of de novo fatty acid synthesis is the distinct signature of epithelial with respect to mesenchymal cells that, on the contrary, show reduced lipogenesis, higher polyunsaturated fatty acids level and increased expression of genes involved in the triglyceride (TAG) synthesis and lipid droplets formation. In the mesenchymal model, the diacylglycerol acyltransferase (DGAT)-1 appears to be the major enzyme involved in TAG synthesis and inhibition of DGAT1, but not DGAT2, drastically reduces the incorporation of labeled palmitate into TAG. Moreover, knockdown of β-catenin demonstrated that this metabolic phenotype in under the control of a network of transcriptional factors and that β-catenin has a specific role in the regulation of lipid metabolism in mesenchymal cells.

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