Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2023.08.20.554007

Transcriptome analyses of mouse cardiac myocytes and non-cardiomyocytes: postmitotic vs. proliferative cells

Takenaka, Y.·Hirasaki, M.·Inoue, I.·Ikeda, M.·Ohata, H.·Kakinuma, Y.
View original source ↗Export metadata ↓

Abstract

Adult heart mostly contains long-lived postmitotic cardiomyocytes and non-cardiomyocytes that have proliferative potential. Here, we isolated cardiomyocytes and non-cardiomyocytes from young and aged mouse heart, and performed transcriptome analyses by RNA sequencing to understand the differences of gene expression in postmitotic and proliferative cells. Gene ontology analyses revealed that genes associated with inflammatory response were upregulated in aged cardiac myocytes, whereas genes including two ATP synthases in mitochondrial respiratory complex V (Atp5l and Atp5J2) and two NADH dehydrogenases in complex I (Ndufa11 and Ndufv3) were significantly downregulated. In aged non-cardiomyocytes, genes related to inflammatory responses were also upregulated, while genes involved in cell cycle and DNA replication process were downregulated. We also found that the expression levels of some small nucleolar RNAs (snoRNAs) are decreased cardiomyocytes with aging. snoRNAs are deeply involved in RNA modification such as pseudouridylation stabilizing ribosomal RNA (rRNA) and mRNA splicing. Therefore, the age-related reduction in snoRNA expression may lead to the destabilization of rRNA, splicing dysfunction, and ultimately a decrease in protein synthesis capacity. A comparison with transcriptome results obtained for non-cardiomyocytes suggests that the decline in the expression of mitochondria-related genes and snoRNAs accompanying aging is specific to cardiomyocytes, implying their potential utility as one of novel aging markers in postmitotic cells.

Explore related subjects

physiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Takenaka, Y., Hirasaki, M., Inoue, I., Ikeda, M., Ohata, H., Kakinuma, Y.. 2023-08-21. Transcriptome analyses of mouse cardiac myocytes and non-cardiomyocytes: postmitotic vs. proliferative cells. https://doi.org/10.1101/2023.08.20.554007

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

IBD-Derived Colonic Fibroblasts Exhibit an Osteopontin-Enriched Secretome, and Osteopontin Restrains Human Colonic Organoid Maturation

Background: Intestinal fibroblasts are extensively remodeled in inflammatory bowel disease (IBD), yet the soluble stromal signals that directly influence epithelial maturation remain incompletely understood. We examined whether fibroblasts derived from inflamed IBD colon display an osteopontin (OPN; SPP1)-enriched secretory phenotype and whether extracellular OPN directly modifies non-neoplastic human colonic epithelium. Methods: Conditioned media from 5 noninflamed-associated fibroblast (NAF) and 4 inflammatory-associated fibroblast (IAF) cultures were analyzed in the validated multi-donor cytokine-array matrix, with orthogonal SPP1 RT-qPCR validation in a complementary fibroblast cohort. Recombinant OPN was then tested in human colonic organoids from 3 donors using donor-resolved molecular and functional analyses under standard, fibroblast-conditioned, and WNT-modified culture conditions. Donor identity defined biological replication. Results: OPN showed the strongest positive rank-based separation between IAF and NAF cultures: all 4 IAF values were higher than all 5 NAF values (Cliff's delta=1.00; exact Mann-Whitney P=0.0159; median ratio=3.64; Benjamini-Hochberg q=.19). Fibroblast RT-qPCR showed approximately 10-fold higher mean SPP1 expression in IAF than NAF cultures (P<.05). In organoids, OPN consistently reduced KRT20, FABP1, CA2, and MUC2 from Day 5 to Day 9. SOX9, HES1, and NOTCH1 increased at Day 9, whereas LGR5 and ALDH provided no evidence of canonical stem-cell expansion. Organoid-area and EdU responses were modest and donor dependent. Conclusions: IBD-derived colonic fibroblasts can display an OPN-enriched secretory phenotype. In human colonic organoids, OPN is sufficient to impair epithelial maturation, whereas its effects on growth and proliferation are variable and depend on the surrounding niche.

physiology↗
bioRxiv2026

A multiscale analysis of liver lobule fibrosis and its impact on drug propagation and metabolism - a DLA approach

Employing DLA methods, this paper explores the self-assembly of collagen fibers and resulting fibrosis at three scales up to the scale of regular lobule models. This allows a mechanistic exploration of the effects of collagen on drug transport (flow and diffusion) and metabolism. In addition, this method permits an analysis of fiber growth characteristics. First, variations of the DLA method of Parkinson et al (1994) will be used to generate multiple explicit collagen microfibril self-assembly using DLA particles in one dimension using cubic grid blocks of (4 mm)3 in a 240 x 20 x 20 grid model. The second stage will be to assess the consequences of various densities of these fibers in three dimensions on flow reductions at a higher scale. Here we utilize DLA methods in cubic grid blocks of (80 nm)3 to mimic 3D collagen self-assembly of fibrils. We then apply a pressure gradient or specified flow rates across a spatially gridded version of these models to quantify flow effects. This region represents a local zone of liver tissue affected by fibrosis. Analytic models of fibrotic effects on flow are employed for comparison. A third stage explores the implications of fibrosis in a liver lobule model using multiple grid blocks of size 3200 mm to represent the lobule tissue. Here, a continuum model of fiber density is employed, based on the previous two scales. The model also includes the effects of additional grid blocks representing sinusoidal flow paths found in the lobule. We contrast and quantify drug propagation and metabolism of molecular dissolved versus nanoparticle delivery vehicles in fibrotic media, achieved by upscaling explicit collagen distributions to appropriate average values.

physiology↗
bioRxiv2026

Pulmonary pressure load shapes right ventricular molecular remodelling in dilated cardiomyopathy

Right ventricular (RV) adaptation to pulmonary hypertension determines outcome in dilated cardiomyopathy (DCM), but the molecular mechanisms of the transition to decompensation remain unclear. We analysed RV tissue from explanted hearts of patients with end-stage DCM using single-nucleus RNA sequencing (n=21), mass spectrometry and Olink Reveal proteomics (both n=44), and integrated these molecular profiles with echocardiographic and right-heart catheterisation measures to identify molecular correlates of RV dysfunction. Mean pulmonary arterial pressure was the dominant correlate of RV transcriptional remodelling, particularly in cardiomyocytes, where higher pressure was associated with contractile remodelling, autophagy, vesicle trafficking and glucose metabolism. In contrast, RV decompensation was characterised by immune activation and reduced oxidative phosphorylation exclusively at the proteomic level. Integrative multi-omics factor analysis (MOFA) further identified fibrosis as the dominant molecular program shared across transcriptomic and proteomic layers. Together, these findings indicate molecular adaptation to pressure load and tissue fibrosis during progression towards RV failure.

physiology↗