Accessing and Assessing the Cell-Surface Glycocalyx Using DNA Origami.

The cell-surface glycocalyx serves as a physiological barrier regulating cellular accessibility to macromolecules and other cells. Conventional glycocalyx characterization has largely been morphological rather than functional. Here, we demonstrated direct glycocalyx anchoring of DNA origami nanotiles and performed a comprehensive comparison with traditional origami targeting to the phospholipid bilayer (PLB) using cholesterol. While DNA nanotiles effectively accessed single-stranded DNA initiators anchored on the glycocalyx, their accessibility to the underlying PLB was only permitted by extended nanotile-to-initiator spacing or by enzymatic glycocalyx degradation using trypsin or pathogenic neuraminidase. Thus, the DNA nanotiles, being expelled by the physiologic glycocalyx, provide an effective functional measure of the glycocalyx barrier integrity and faithfully predict cell-to-cell accessibility during DNA-guided multicellular assembly. Lastly, the glycocalyx-anchoring mechanism enabled enhanced cell-surface stability and cellular uptake of nanotiles compared to PLB anchoring. This research lays the foundation for future development of DNA nanodevices to access the cell surface.

Adipose Tissue Paracrine-, Autocrine-, and Matrix-Dependent Signaling during the Development and Progression of Obesity.

Obesity is an ever-increasing phenomenon, with 42% of Americans being considered obese (BMI ≥ 30) and 9.2% being considered morbidly obese (BMI ≥ 40) as of 2016. With obesity being characterized by an abundance of adipose tissue expansion, abnormal tissue remodeling is a typical consequence. Importantly, this pathological tissue expansion is associated with many alterations in the cellular populations and phenotypes within the tissue, lending to cellular, paracrine, mechanical, and metabolic alterations that have local and systemic effects, including diabetes and cardiovascular disease. In particular, vascular dynamics shift during the progression of obesity, providing signaling cues that drive metabolic dysfunction. In this review, paracrine-, autocrine-, and matrix-dependent signaling between adipocytes and endothelial cells is discussed in the context of the development and progression of obesity and its consequential diseases, including adipose fibrosis, diabetes, and cardiovascular disease.

Adipose Tissue Development Relies on Coordinated Extracellular Matrix Remodeling, Angiogenesis, and Adipogenesis.

Despite developing prenatally, the adipose tissue is unique in its ability to undergo drastic growth even after reaching its mature size. This development and subsequent maintenance rely on the proper coordination between the vascular niche and the adipose compartment. In this review, the process of adipose tissue development is broken down to explain (1) the ultrastructural matrix remodeling that is undertaken during simultaneous adipogenesis and angiogenesis, (2) the paracrine crosstalk involved during adipose development, (3) the mechanical regulators involved in adipose growth, and (4) the proteolytic and paracrine oversight for matrix remodeling during adipose development. It is crucial to gain a better understanding of the complex relationships that exist between adipose tissue and the vasculature during tissue development to provide insights into the pathological tissue expansion of obesity and to develop improved soft-tissue reconstruction techniques.

Recapitulating human cardio-pulmonary co-development using simultaneous multilineage differentiation of pluripotent stem cells.

The extensive crosstalk between the developing heart and lung is critical to their proper morphogenesis and maturation. However, there remains a lack of models that investigate the critical cardio-pulmonary mutual interaction during human embryogenesis. Here, we reported a novel stepwise strategy for directing the simultaneous induction of both mesoderm-derived cardiac and endoderm-derived lung epithelial lineages within a single differentiation of human-induced pluripotent stem cells (hiPSCs) via temporal specific tuning of WNT and nodal signaling in the absence of exogenous growth factors. Using 3D suspension culture, we established concentric cardio-pulmonary micro-Tissues (µTs), and expedited alveolar maturation in the presence of cardiac accompaniment. Upon withdrawal of WNT agonist, the cardiac and pulmonary components within each dual-lineage µT effectively segregated from each other with concurrent initiation of cardiac contraction. We expect that our multilineage differentiation model will offer an experimentally tractable system for investigating human cardio-pulmonary interaction and tissue boundary formation during embryogenesis.

Organs begin developing during the first few months of pregnancy, while the baby is still an embryo. These early stages of development are known as embryogenesis ­ a tightly organized process, during which the embryo forms different layers of stem cells. These cells can be activated to turn into a particular type of cell, such as a heart or a lung cell. The heart and lungs develop from different layers within the embryo, which must communicate with each other for the organs to form correctly. For example, chemical signals can be released from and travel between layers of the embryo, activating processes inside cells located in the different areas. In mouse models, chemical signals and cells travel between developing heart and lung, which helps both organs to form into the correct structure. But it is unclear how well the observations from mouse models translate to heart and lung development in humans. To find out more, Ng et al. developed a human model of heart and lung co-development during embryogenesis using human pluripotent stem cells. The laboratory-grown stem cells were treated with chemical signals, causing them to form different layers that developed into early forms of heart and lung cells. The cells were then transferred into a specific growing condition, where they arranged into three-dimensional structures termed microtissues. Ng et al. found that lung cells developed faster when grown in microtissues with accompanying developing heart cells compared to microtissues containing only developing lung cells. In addition, Ng et al. revealed that the co-developing heart and lung tissues automatically separate from each other during later stage, without the need for chemical signals. This human cell-based model of early forms of co-developing heart and lung cells may help provide researchers with new strategies to probe the underlying mechanisms of human heart and lung interaction during embryogenesis.