Effects of Spaceflight and Simulated Microgravity on YAP1 Expression in Cardiovascular Progenitors: Implications for Cell-Based Repair.

Victor Camberos,Larry V Lopez,Nahidh Hasaniya,Leonard Bailey,Mary Kearns-Jonker,Jonathan Baio

doi:10.3390/ijms20112742

Victor Camberos, Larry V Lopez + Show 4 more

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https://doi.org/10.3390/ijms20112742

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Abstract

Spaceflight alters many processes of the human body including cardiac function and cardiac progenitor cell behavior. The mechanism behind these changes remains largely unknown; however, simulated microgravity devices are making it easier for researchers to study the effects of microgravity. To study the changes that take place in cardiac progenitor cells in microgravity environments, adult cardiac progenitor cells were cultured aboard the International Space Station (ISS) as well as on a clinostat and examined for changes in Hippo signaling, a pathway known to regulate cardiac development. Cells cultured under microgravity conditions, spaceflight-induced or simulated, displayed upregulation of downstream genes involved in the Hippo pathway such as YAP1 and SOD2. YAP1 is known to play a role in cardiac regeneration which led us to investigate YAP1 expression in a sheep model of cardiovascular repair. Additionally, to mimic the effects of microgravity, drug treatment was used to induce Hippo related genes as well as a regulator of the Hippo pathway, miRNA-302a. These studies provide insight into the changes that occur in space and how the effects of these changes relate to cardiac regeneration studies.

Highlights

Space exploration is expanding rapidly and broadening our understanding of the world around us, as well as the cells within us
Several cell types have been cultured in space such as bone marrow progenitor cells [2], mouse embryonic stem cells [5], endothelial cells [3], and human cardiac progenitor cells (CPCs) [4]
Cell clones were isolated by single cell expansion and screened for the expression of markers specific to early cardiac progenitor cells as previously reported by our laboratory [30]

Summary

Introduction

Space exploration is expanding rapidly and broadening our understanding of the world around us, as well as the cells within us. Several cell types have been cultured in space such as bone marrow progenitor cells [2], mouse embryonic stem cells [5], endothelial cells [3], and human cardiac progenitor cells (CPCs) [4]. Culture in microgravity conditions has been shown to cause hypertrophy in osteoblast cells [6] and inhibits differentiation in mouse embryonic stem cells [5], but beneficial effects include an increase in the expression of transcripts encoding DNA repair genes in human fibroblasts [7] and an increase in migratory capacity in CPCs [4]. This study emphasizes the finding that transcriptional alterations in space can influence cell responses upon return to normal gravity and that the duration of exposure plays a significant role in the biological impact of microgravity. Alternative methods of studying microgravity play an important role in understanding the impact of microgravity on cell biology and how this information may be applied on Earth as well as in space

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