SNIC
SUPR
SNIC SUPR
Newt Heart Regeneration Single Cell Sequencing
Dnr:

SNIC 2018/8-45

Type:

SNAC Small

Principal Investigator:

Kenneth Chien

Affiliation:

Karolinska Institutet

Start Date:

2018-03-22

End Date:

2019-04-01

Primary Classification:

10604: Cell Biology

Webpage:

Allocation

Abstract

Heart disease is the leading cause of mortality worldwide due to the limited regenerative capacity of the mammalian heart. Myocardial infarction causes massive cardiomyocyte apoptosis that is replaced by a fibrotic scar. Although fibrosis prevents ventricular wall rupture, its accumulation causes cardiac hypertrophy leading to heart failure, underlining the need for therapeutic strategies to resolve fibrosis. How to augment the fibrotic environment following a heart attack remains elusive. In contrast to mammals, certain vertebrates such as fish and amphibians can regenerate cardiac muscle without scarring. We are interested in studying cardiac regeneration and fibrosis reversal in the urodele amphibian species Pleurodeles waltl. We established a cryoinjury model that mimics the myocardial infarction in mammals and observed that similar to mammalian heart there is a great fibrotic response in the P. waltl heart following the injury. However, unlike the mammals, P. waltl is capable of reversing the fibrosis and regenerating the cardiac muscle. As we lack functional markers for the various cell types responsible for this phenotype, we collected single cells from uninjured and injured P. waltl hearts to perform single-cell sequencing experiments. Further functional studies will be performed with the candidates obtained from this analysis to identify key components of regeneration and fibrosis reversal. As fibrosis affects other organs such as kidney, liver and lung, impairing their function and causing a variety of debilitating diseases, analyzing the cellular and molecular mechanisms of cardiac fibrosis reversal will not only help treating heart disease but also benefit developing strategies to reverse organ fibrosis in general.