Yörüngesel uzay uçuşu sırasında PBMC’lerde PIN1 ile ilişkili bir gen panelinin keşifsel boylamsal analizi

Abstract

Uzay uçuşu, mikrogravite, radyasyon, sirkadiyen düzensizlik, izolasyon ve operasyonel stresin birlikte etkili olduğu çok faktörlü fizyolojik bir ortam oluşturmaktadır. Bu keşifsel çalışmada, Axiom-3 görevine katılan üç astronottan fırlatma öncesinde (L−7) ve Uluslararası Uzay İstasyonu’ndaki 4., 7. ve 10. günlerde alınan periferik kan mononükleer hücrelerine ait RNA dizileme verileri incelenmiştir. Fırlatma öncesinde ve suborbital uçuştan 3 saat sonra örneklenen ayrı bir Galactic-07 katılımcısı yalnızca tanımlayıcı bağlamda değerlendirilmiştir. Analiz, PIN1 ve hücre döngüsü, stres yanıtı, transkripsiyonel kontrol, doğuştan bağışıklık ve oksidatif yanıtlarla biyolojik olarak ilişkili diğer 10 gen olmak üzere toplam 11 genden oluşan önceden belirlenmiş bir panele odaklanmıştır. Katılımcı etkisini dikkate alan boylamsal analiz ve Benjamini–Hochberg düzeltmesi sonrasında PIN1, TP53, PML, MYC, NCF1, NCF2, IRF3, POLR2A ve SFN için zamanla ilişkili anlamlı değişiklikler belirlenmiştir. Bazı diğer genlerde aşağı yönlü tanımlayıcı ekspresyon örüntüleri gözlenmekle birlikte, bu değişiklikler çoklu test düzeltmesi sonrasında anlamlılık sınırına ulaşmamıştır. Küçük örneklem büyüklüğü ve ölçümlerin toplu PBMC mRNA düzeyiyle sınırlı olması nedeniyle bulgular PIN1 protein aktivitesindeki değişimi, göreve özgü düzenleyici bir ağı veya biyobelirteç performansını göstermemektedir. Sonuçlar, daha büyük astronot kohortlarında protein düzeyi, fonksiyonel ve hücre tipi çözünürlüklü analizlerle değerlendirilmesi gereken hipotez üretici transkripsiyonel örüntüler sunmaktadır.

Keywords

• PIN1 merkezli ağ
• Mikrogravite
• Uzay uçuşu transkriptomiği
• PBMC gen ekspresyonu
• Bağışıklık ve stres yanıtı

Project Number

1007-KAMAG-121L002 / Agreement No: TABM-HZT-23-25

Exploratory longitudinal analysis of a PIN1-associated gene panel in PBMCs during orbital spaceflight

Abstract

Spaceflight exposes astronauts to a combination of microgravity, radiation, circadian disruption, isolation, and operational stress that may influence immune and transcriptional regulation. In this exploratory study, we examined peripheral blood mononuclear cell RNA-sequencing data from three Axiom-3 astronauts sampled before launch (L−7) and on International Space Station Days 4, 7, and 10. A separate Galactic-07 participant sampled before launch and 3 h after suborbital flight was included for descriptive context only. The analysis focused on a preselected panel comprising PIN1 and ten biologically associated genes involved in cell-cycle regulation, stress responses, transcriptional control, innate immunity, and oxidative responses. Participant-adjusted longitudinal analysis identified significant overall time-associated variation in PIN1, TP53, PML, MYC, NCF1, NCF2, IRF3, POLR2A, and SFN after Benjamini–Hochberg correction. Several additional genes exhibited descriptive downward expression patterns without meeting the adjusted significance threshold. Because the cohort was small and the measurements were limited to bulk-PBMC mRNA abundance, the findings do not establish altered PIN1 protein activity, a mission-specific regulatory network, or biomarker performance. Instead, they provide hypothesis-generating evidence supporting further evaluation of PIN1-associated transcriptional responses in larger astronaut cohorts using protein-level, functional, and cell-type-resolved analyses.

Keywords

• PIN1-centered network
• Microgravity
• Spaceflight transcriptomics
• PBMC gene expression
• Immune and stress response

Supporting Institution

Through the Turkish Astronaut and Scientific Mission (TABM) Project (1007-KAMAG-121L002/Agreement No: TABM-HZT-23-25), the Scientific and Technological Research Council of Türkiye (TUBITAK) and the Turkish Space Agency (TUA) provided funding for this project.

Project Number

1007-KAMAG-121L002 / Agreement No: TABM-HZT-23-25

Ethical Statement

This article meets the standards of research and publication ethics.

Thanks

The infrastructure and experience created by these initiatives prepared the way for involvement in the MESSAGE Science Mission. We sincerely thank the Scientific and Technological Research Council of Türkiye (TUBITAK), the Turkish Space Agency (TUA) and Üsküdar University for their assistance during this process. The opinions and findings expressed in this publication are solely those of the authors and do not necessarily reflect the official views of the supporting institutions. Finally, we extend our sincere thanks to all research colleagues, data analysts, and technical staff whose contributions were essential to the success of the MESSAGE Science Mission.

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