ICELL8 technology keeps cardiovascular research pumping

Cardiovascular disease has been the number one cause of death in the world for the last fifteen years or more (Wang, H. et al. 2016; WHO, 2018; Heron, 2019), and researchers are using single-cell transcriptomics to better understand the cells that comprise the heart muscle—both cardiomyocytes (CMs) and non-cardiomyocytes (non-CMs)—to find new treatments for cardiomyopathies. However, due to the size and irregular shape of cardiomyocytes, isolation can be a challenge, especially when high-throughput is desirable. Many automated dispensers rupture the cell membranes due to narrow dispense apertures or other structural limitations.

The solution for some cardiac researchers has been to turn to the ICELL8 Single-Cell System. The unique large-bore multisample nanodispenser has been used successfully for gentler handling of the large cell types required in their studies, providing greater confidence in having sufficient candidates for downstream analysis after single-cell isolation. In this blog, we will discuss two recent publications from Fuwai Hospital in Beijing, both on the topic of hypertrophy.

In a January 2020 Nature article, Wang, L. et al. recognized a lack of a clear cellular map of the heart, which makes it difficult to characterize the cellular behaviors related to cardiac function. Using the ICELL8 system's prevalidated 3′ DE application, they looked at both CMs and non-CMs in normal, hypertrophic, and partially recovered mouse hearts and were able to capture, visualize, and study >12,000 cells across 14 donors. Through transcriptome profiling, they identified heterogeneity with cardiomyocytes in atrial and ventricular areas of the heart.

Ren et al. took this research a step further with the goal of finding pharmaceutical treatments that can help mitigate cardiac disease, publishing their findings in the American Heart Association's Circulation in February 2020. They set out to look at the transcriptomes of cardiomyocytes through their progression of normal to hypertrophic state, and their interaction with non-CM cells. They used the ICELL8 system to separate cells into subtypes using in vivo mouse models, and then, after staining with Hoechst and propidium iodide, leveraged the imaging function of the system to categorize wells containing single cells in the nanowell plate. Identifying isolated cardiomyocytes allowed them to select which wells to target for downstream library prep, eliminating excess use of reagents and ensuring sufficient, validated samples for sequencing.

These two new studies by Fuwai Hospital, using the ICELL8 system, have provided valuable insights into the nature of cardiac hypertrophy. While the heart of the matter hasn't been pinned down yet, studies like these are a beat in the path to reaching it.

Large and oddly-shaped cells like cardiomyocytes are gently dispensed by the large-bore nozzle of the ICELL8 system, aiding researchers in isolating this cell type.

References:

Wang, H. et al. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet (2016).

World Health Organization. Global Health Estimates 2016: Deaths by Cause, Age, Sex, by Country and by Region, 2000–2016. Geneva. World Health Organization (2018).

Heron, M. National Vital Statistics Reports Volume 68, Number 6, June 24, 2019, Deaths: Leading Causes for 2017. National Vital Statistics Reports (2019).

Wang, L. et al. Single-cell reconstruction of the adult human heart during heart failure and recovery reveals the cellular landscape underlying cardiac function. Nat. Cell Biol. 22, 108–119 (2020).

Ren, Z. et al. Single-Cell Reconstruction of Progression Trajectory Reveals Intervention Principles in Pathological Cardiac Hypertrophy. Circulation https://doi.org/10.1161/CIRCULATIONAHA.119.043053 (2020).