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. 2021 Mar 30;22(7):3577.
doi: 10.3390/ijms22073577.

The Impact of Spaceflight and Microgravity on the Human Islet-1+ Cardiovascular Progenitor Cell Transcriptome

Victor Camberos  1 , Jonathan Baio  1 , Ana Mandujano  1 , Aida F Martinez  1 , Leonard Bailey  2 , Nahidh Hasaniya  2 , Mary Kearns-Jonker  1
Affiliations

The Impact of Spaceflight and Microgravity on the Human Islet-1+ Cardiovascular Progenitor Cell Transcriptome

Victor Camberos et al. Int J Mol Sci. .

Abstract

Understanding the transcriptomic impact of microgravity and the spaceflight environment is relevant for future missions in space and microgravity-based applications designed to benefit life on Earth. Here, we investigated the transcriptome of adult and neonatal cardiovascular progenitors following culture aboard the International Space Station for 30 days and compared it to the transcriptome of clonally identical cells cultured on Earth. Cardiovascular progenitors acquire a gene expression profile representative of an early-stage, dedifferentiated, stem-like state, regardless of age. Signaling pathways that support cell proliferation and survival were induced by spaceflight along with transcripts related to cell cycle re-entry, cardiovascular development, and oxidative stress. These findings contribute new insight into the multifaceted influence of reduced gravitational environments.

Keywords: cardiovascular; miRNA; microgravity; proliferation; spaceflight; stemness; transcriptomics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Induced transcripts from flown adult (left) and neonatal (right) cardiovascular progenitor cells were separated by fold change. (A) The distribution of upregulated transcripts in each fold change category is shown for flown adult CPCs. (B) KEGG analysis of transcripts with a fold change of 2–4.99, (C) 4–9.99, (D) 10–24.99, and (E) 25+ in flown adult CPCs. (F) The distribution of upregulated transcripts in each fold change category is shown for flown neonatal CPCs. (G) KEGG analysis of transcripts with a fold change of 2–4.99, (H) 4–9.99, (I) 10–24.99, and (J) 25+ in flown neonatal CPCs.
Figure 2
Figure 2
Spaceflight induces transcripts related to stemness. (A) StemChecker shows an increase in overlapping iPSC stemness markers in flown CPCs. (B) Other established stemness markers were impacted by spaceflight. (C) Differential gene expression in flown samples and ground controls in adult CPCs and (D) neonatal CPCs. (E) GPCR signaling was induced in CPCs cultured aboard the ISS. Individual fold changes for adult and neonatal groups are presented superimposed for comparison.
Figure 3
Figure 3
Spaceflight induced senescence genes that also play a role in stemness. (A) Adult CPCs induced 16% of senescence genes found in the CellAge database. (B) Ten senescence-inducing genes and five inhibiting genes were unique to the adult CPCs. (C) Neonatal CPCs induced 16% of CellAge senescence genes. (D) Sixteen genes were unique to neonatal CPCs: 12 inducing, 4 inhibiting. (E) Senescence-inducing genes that were shared between both age groups have dual roles in cell survival and proliferation.
Figure 4
Figure 4
Pathways related to survival and proliferation were positively induced by spaceflight. Representative pathways include (A) Notch, (B) ERBB, (C) Wnt, and (D) Hippo.
Figure 5
Figure 5
Gene transcripts associated with repair mechanisms were induced in flown CPCs compared to ground controls. Reparative processes that were induced by spaceflight include (A) cell cycle, (B) differentiation, (C) heart development, (D) oxidative stress, and (E) focal adhesion.
Figure 6
Figure 6
Predicted targets of miRNAs induced by spaceflight impact pathways related to cell cycle progression and survival. Differentially expressed miRNAs from flown adult and neonatal CPCs were mapped on a network using miRNet. KEGG analysis of predicted gene targets from adult and neonatal miRNAs reflects relevant regeneration and repair pathways.
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