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Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics [spatial]

ABSTRACT: We use spatial transcriptomics to establish regional transcriptional profile of neonatal heart tissue obtained at indicated timpoints after apical resection surgery.

ORGANISM(S): Mus musculus

PROVIDER: GSE188888 | GEO | 2021/12/20

REPOSITORIES: GEO

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Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics [RNA-seq]

Project description:We report the transcriptional changes occuring in fibroblasts obtained from mouse hearts subjected to apical resection surgery or sham surgery, compared to unmanipulated controls, at indicated timepoints.

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Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics.

Project description:The neonatal mammalian heart exhibits a remarkable regenerative potential, which includes fibrotic scar resolution and the generation of new cardiomyocytes. To investigate the mechanisms facilitating heart repair after apical resection in neonatal mice, we conducted bulk and spatial transcriptomic analyses at regenerative and non-regenerative timepoints. Importantly, spatial transcriptomics provided near single-cell resolution, revealing distinct domains of atrial and ventricular myocardium that exhibit dynamic phenotypic alterations during postnatal heart maturation. Spatial transcriptomics also defined the cardiac scar, which transitions from a proliferative to secretory phenotype as the heart loses regenerative potential. The resolving scar is characterized by spatially and temporally restricted programs of inflammation, epicardium expansion and extracellular matrix production, metabolic reprogramming, lipogenic scar extrusion, and cardiomyocyte restoration. Finally, this study revealed the emergence of a regenerative border zone defined by immature cardiomyocyte markers and the robust expression of Sprr1a. Taken together, our study defines the spatially and temporally restricted gene programs that underlie neonatal heart regeneration and provides insight into cardio-restorative mechanisms supporting scar resolution.

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Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics

Project description:This SuperSeries is composed of the SubSeries listed below.

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Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics [spatial]

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Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics

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Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics [RNA-seq]

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Murine neonatal cardiac B cells promote cardiomyocyte proliferation and heart regeneration

Project description:Since the proliferative capacity of cardiomyocytes is extremely limited in the adult mammalian hearts, the irreversible loss of cardiomyocytes following cardiac injury markedly reduces cardiac function, leading to cardiac remodeling and heart failure. However, the early neonatal mice have a strong ability in cardiomyocyte proliferation and cardiac regeneration after heart damage such as apical resection. Besides of cardiomyocytes, non-myocytes in heart tissue also play important roles in the regeneration process. Previous studies showed that cardiac macrophages, regulatory T cells and CD4+ T cells are all involved in regulating the myocardial regeneration process. However, the roles of other cardiac immune cells in cardiac regeneration remains to be elucidated. B cells is a prominent immune cell in injured heart; here we discovered the indispensable function of cardiac B cells in improving cardiomyocyte proliferation and heart regeneration in neonatal mice.

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Expression data from neonatal heart after apex resection

Project description:Apical resection in 1-day-old mice results in complete regenerated heart and normal cardiac function, which is characterized by significant cardiomyocyte proliferation with minimal fibrosis. Local damage on hearts of 1-day-old mice can amplify cardiomyocyte proliferation located in the whole ventricle rather than limited damage area. This response provides a reasonable screening model to identify novel genes involved in endogenous cardiac regeneration

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RNA seq analysis of regenerating hearts from three models of successful cardiac regeneration

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