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Single cell transcriptomic analysis of embyronic hearts with fibroblast ablation

ABSTRACT: single cell transcriptomic analysis of embyronic hearts with fibroblast ablation

PROVIDER: PRJNA1134740 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29791535_1.fastq.gz	Fastqsanger.gz
	SRR29791535_2.fastq.gz	Fastqsanger.gz
	SRR29791536_1.fastq.gz	Fastqsanger.gz
	SRR29791536_2.fastq.gz	Fastqsanger.gz
	SRR29791537_1.fastq.gz	Fastqsanger.gz

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Consequences of fibroblast ablation in adult murine hearts

Project description:Fibroblasts produce the majority of collagen in the heart and are thought to regulate extracellular matrix (ECM) turnover. However, the in vivo role of fibroblasts in structuring the basal ECM network is poorly understood. To examine the effects of fibroblast loss on the microenvironment in the adult murine heart, we generated mice with reduced fibroblast numbers and evaluated the tissue microenvironment during homeostasis and after injury. We determined that a 60-80% reduction in fibroblasts numbers did not overtly change the fibrillar collagen network but did alter the distribution and abundance of type VI collagen, a microfibrillar collagen that forms an open network with the basement membrane. In fibroblast ablated mice, myocardial infarction did not result in ventricular wall rupture, and heart function was more effectively preserved during angiotensin II/phenylephrine (AngII/PE) induced fibrosis. Analysis of cardiomyocyte contractility demonstrated weaker contractions and slower calcium release and reuptake in uninjured and AngII/PE infused fibroblast ablated animals. Moreover, fibroblast ablated hearts have a similar gene expression prolife to hearts with exercise-induced and physiological hypertrophy after AngII/PE infusion. These results suggest that hearts are resilient to a significant degree of fibroblast loss and that fibroblasts can directly impact cardiomyocyte function. Furthermore, a reduction in fibroblasts may have cardioprotective effects heart after injury suggesting that manipulation of the number of fibroblasts may have therapeutic value.

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single cell transcriptomic analysis of embyronic hearts with fibroblast ablation

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RNA-sequencing of unstressed and pressure-overloaded C57 mouse hearts with single or combined ablation of PKCdelta and PKCepsilon

Project description:Combinatorial ablation of the major cardiac-expressed novel protein kinase C isoforms, PKCdelta and PKCepsilon, in murine cadiac myocytes unmasked functionally redundant growth-limiting effects of these kinases in hemodynamically stressed adult hearts and during normal embryonic cardiac development, mediated in part by shared transcriptional de-repression of ERK and periostin signaling. 14 cardiac polyA+-RNA profiles from unstressed, 12 week-old C57BL/6J-background mice (4 wild-type, 3 postnatal cardiac PKCdelta ablation, 3 germline PKCepsilon knockout, 4 combined knockouts) and 15 profiles generated 4 weeks after TAC induction (4 wild-type, 3 PKCdelta, 4 PKCepsilon, 4 combined knockout) were generated on Illumina HiSeq 2000 instruments.

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