Publications by authors named "Joshua H Lee"
Regulation of sarcomere formation and function in the healthy heart requires a titin intronic enhancer.
J Clin Invest
December 2024
Heterozygous truncating variants in the sarcomere protein titin (TTN) are the most common genetic cause of heart failure. To understand mechanisms that regulate abundant cardiomyocyte (CM) TTN expression, we characterized highly conserved intron 1 sequences that exhibited dynamic changes in chromatin accessibility during differentiation of human CMs from induced pluripotent stem cells (hiPSC-CMs). Homozygous deletion of these sequences in mice caused embryonic lethality, whereas heterozygous mice showed an allele-specific reduction in Ttn expression.
View Article and Find Full Text PDFNatural tissues are composed of diverse cells and extracellular materials whose arrangements across several length scales-from subcellular lengths (micrometre) to the organ scale (centimetre)-regulate biological functions. Tissue-fabrication methods have progressed to large constructs, for example, through stereolithography and nozzle-based bioprinting, and subcellular resolution through subtractive photoablation. However, additive bioprinting struggles with sub-nozzle/voxel features and photoablation is restricted to small volumes by prohibitive heat generation and time.
View Article and Find Full Text PDFArticle Synopsis
- Hypertrophic cardiomyopathy (HCM) involves thickening of the heart's left ventricular wall and is related to mutations in genes affecting sarcomere proteins.
- Researchers used engineered cardiac microtissues (CMTs) made of HCM-variant cardiomyocytes and healthy fibroblasts to study how these cells interact, revealing that fibroblast proliferation contributes to increased collagen and tissue stiffness.
- The study found that signals from the HCM-variant cardiomyocytes stimulate fibroblast growth, and blocking certain receptors can reduce this effect, highlighting a potential mechanism for the fibrotic changes seen in patients with HCM.
Article Synopsis
- - Tissue engineering aims to create vascularized tissues quickly, but existing methods struggle with balancing detail and speed, making them inefficient for scale.
- - A new technique called SPAN uses a unique approach to form a network of small, perfusable channels in tissues within minutes, regardless of the tissue's size.
- - SPAN allows for the seamless integration of functional blood vessels into tissue constructs and enables rapid assembly while supporting multiple cell types, advancing the future of tissue engineering.