title: Microgravity Reduces the Differentiation and Regenerative Potential of Embryonic Stem Cells.
abstract: Mechanical unloading in microgravity is thought to induce tissue degeneration by various mechanisms, including inhibition of regenerative stem cell differentiation. To address this hypothesis, we investigated the effects of microgravity on early lineage commitment of mouse embryonic stem cells (mESCs) using the embryoid body (EB) model of tissue differentiation. We found that exposure to microgravity for 15 days inhibits mESC differentiation and expression of terminal germ layer lineage markers in EBs. Additionally, microgravity-unloaded EBs retained stem cell self-renewal markers, suggesting that mechanical loading at Earth's gravity is required for normal differentiation of mESCs. Finally, cells recovered from microgravity-unloaded EBs and then cultured at Earth's gravity showed greater stemness, differentiating more readily into contractile cardiomyocyte colonies. These results indicate that mechanical unloading of stem cells in microgravity inhibits their differentiation and preserves stemness, possibly providing a cellular mechanistic basis for the inhibition of tissue regeneration in space and in disuse conditions on earth.
authors.affiliation: 1 Space Biosciences Division, NASA Ames Research Center , Moffett Field, California.|2 School of Biotechnology and Biomolecular Sciences, University of New South Wales , Sydney, Australia .
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Blaber
authors.affiliation: 1 Space Biosciences Division, NASA Ames Research Center , Moffett Field, California.
authors.forename: Hayley
authors.initials: H
authors.lastname: Finkelstein
authors.affiliation: 1 Space Biosciences Division, NASA Ames Research Center , Moffett Field, California.
authors.forename: Natalya
authors.initials: N
authors.lastname: Dvorochkin
authors.affiliation: 3 FILMSS Wyle, Space Biology, NASA Ames Research Center , Moffett Field, California.
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Sato
authors.affiliation: 1 Space Biosciences Division, NASA Ames Research Center , Moffett Field, California.
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Yousuf
authors.affiliation: 2 School of Biotechnology and Biomolecular Sciences, University of New South Wales , Sydney, Australia .|4 Australian Centre for Astrobiology, University of New South Wales , Sydney, Australia .
authors.forename: Brendan P
authors.initials: BP
authors.lastname: Burns
authors.affiliation: 1 Space Biosciences Division, NASA Ames Research Center , Moffett Field, California.
authors.forename: Ruth K
authors.initials: RK
authors.lastname: Globus
authors.affiliation: 1 Space Biosciences Division, NASA Ames Research Center , Moffett Field, California.
authors.forename: Eduardo A C
authors.initials: EA
authors.lastname: Almeida
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D058732:Embryoid Bodies / Q000166:cytology*; D051379:Mice; D014893:Weightlessness