Abstract
There have been many studies on the biological effects of simulated microgravity (SMG) on differentiated cells or adult stem cells. However, there has been no systematic study on the effects of SMG on embryonic stem (ES) cells. In this study, we investigated various effects (including cell proliferation, cell cycle distribution, cell differentiation, cell adhesion, apoptosis, genomic integrity and DNA damage repair) of SMG on mouse embryonic stem (mES) cells. Mouse ES cells cultured under SMG condition had a significantly reduced total cell number compared with cells cultured under 1 g gravity (1G) condition. However, there was no significant difference in cell cycle distribution between SMG and 1G culture conditions, indicating that cell proliferation was not impaired significantly by SMG and was not a major factor contributing to the total cell number reduction. In contrast, a lower adhesion rate cultured under SMG condition contributed to the lower cell number in SMG. Our results also revealed that SMG alone could not induce DNA damage in mES cells while it could affect the repair of radiation-induced DNA lesions of mES cells. Taken together, mES cells were sensitive to SMG and the major alterations in cellular events were cell number expansion, adhesion rate decrease, increased apoptosis and delayed DNA repair progression, which are distinct from the responses of other types of cells to SMG.
Highlights
Spaceflight results in a number of adverse effects such as bone loss [1], skeletal muscle atrophy [2], cardiovascular problems [3], immune system dysregulation [4], and alteration of sleep and circadian rhythms [5]
On day 2 and day 7 of the rotation, there was no significant difference between the simulated microgravity (SMG) group and the 1 g gravity (1G) group cells in the expression of these two genes (Figure 1B), confirming that the culture under SMG condition did not induce differentiation of mouse embryonic stem (mES) cells
We have systematically investigated the effects of SMG on mES cells and we found that mES cells were sensitive to SMG and the major alterations in cellular events were population growth inhibition, decreased adhesion rate, increased apoptosis and delayed DNA repair progression, which are unique to the responses of other types of cells to SMG
Summary
Spaceflight results in a number of adverse effects such as bone loss [1], skeletal muscle atrophy [2], cardiovascular problems [3], immune system dysregulation [4], and alteration of sleep and circadian rhythms [5]. Many of the above mentioned problems are due to the effects of MG at cellular level. Because of the cost effectiveness and limited access to space flight, simulating MG on Earth is widely used in space life research. A 3D clinostat is a device that generates multidirectional G force and cancels the cumulative gravity, effectively simulating certain aspects of MG. Using such devices, detailed experiments have been performed towards the understanding of the effects of MG on many cellular activities
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