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Simulated Microgravity Reprograms Human Megakaryocyte Biology: Phenotypic, Transcriptomic, and Autophagic Evidence from a Ground-Based Analogue Study

Year: 2026

Type: article

Abstract: Megakaryocytes (MKs) integrate inflammatory, immune, and hemostatic functions, and their dysregulation may promote inflammation and thrombosis, key risks for spaceflight crew health. Despite this relevance, MK responses to spaceflight-related gravitational changes remain poorly defined. Using a NASA-approved randomizing gravitational-vector system (RCCS), CD34⁺ hematopoietic progenitor cells were differentiated into MKs under simulated microgravity conditions. Viability, proliferation, proplatelet formation, morphology, flow cytometry, and transcriptomic profiling (RNA-seq) were used to identify gravity-sensitive processes. Simulated microgravity altered MK growth dynamics and showed a trend toward reduced viability, and flow cytometry demonstrated significantly enhanced expression of megakaryocytic maturation markers. Microgravity conditions further revealed disrupted autophagic flux indicative of an early-stage inhibition. RNA-seq identified significant transcriptional changes involving immune and inflammatory signaling, transcription, protein biogenesis, lipid regulation, and mitochondrial management. Together, these findings uncover previously unrecognized gravitational control of MK development and function, addressing critical knowledge gaps in spaceflight-associated thromboinflammatory risk and informing countermeasure development for long-duration and deep-space missions.

Source: Life Sciences in Space Research

DOI: 10.1016/j.lssr.2026.11.001