Quantitative analyses of single mitochondrial components reveal an early role of small-mitochondrial-networks in priming neoplasticity.

Unlabelled: Quantitative understanding of mitochondrial heterogeneity is necessary for elucidating the precise role of these multifaceted organelles in tumor cell development. We demonstrate an early mechanistic role of mitochondria in initiating neoplasticity by performing quantitative analyses of structure-function of single mitochondrial components coupled with single cell transcriptomics. We demonstrate that the large Hyperfused-Mitochondrial-Networks (HMNs) of keratinocytes promptly get converted to the heterogenous Small-Mitochondrial-Networks (SMNs) as the stem cell enriching dose of the model carcinogen, TCDD, depolarizes mitochondria.

Direct cardiac reprogramming via combined CRISPRa-mediated endogenous Gata4 activation and exogenous Mef2c and Tbx5 expression.

Direct cardiac reprogramming of fibroblasts into induced cardiomyocytes (iCMs) can be achieved by ectopic expression of cardiac transcription factors (TFs) via viral vectors. However, risks like genomic mutations, viral toxicity, and immune response limited its clinical application. Transactivation of endogenous TFs emerges as an alternative approach that may partially mitigate some of the risks.

Cardiac Aging in the Multi-Omics Era: High-Throughput Sequencing Insights.

Cardiovascular diseases are a leading cause of mortality worldwide, and the risks of both developing a disease and receiving a poor prognosis increase with age. With increasing life expectancy, understanding the mechanisms underlying heart aging has become critical. Traditional techniques have supported research into finding the physiological changes and hallmarks of cardiovascular aging, including oxidative stress, disabled macroautophagy, loss of proteostasis, and epigenetic alterations, among others.

Single-cell chromatin profiling reveals genetic programs activating proregenerative states in nonmyocyte cells.

Cardiac regeneration requires coordinated participation of multiple cell types whereby their communications result in transient activation of proregenerative cell states. Although the molecular characteristics and lineage origins of these activated cell states and their contribution to cardiac regeneration have been studied, the extracellular signaling and the intrinsic genetic program underlying the activation of the transient functional cell states remain largely unexplored. In this study, we delineated the chromatin landscapes of the noncardiomyocytes (nonCMs) of the regenerating heart at the single-cell level and inferred the cis-regulatory architectures and trans-acting factors that control cell type-specific gene expression programs.