Nodal/SMAD2 and Bone Morphogenic Protein 4 RNA Expression in Microgravity. Implications for Spacial Orientation Signaling in Hematopoesis and the Implications for the Hematosuppressive Effects of Space Flight

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.4286-4286
• Main Author: Spigelman, Zachary Simon
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-149904

Introduction: Nodal proteins are members of the TGF alpha family which direct right left orientation in the developing embryo. Nodal/SMAD2 signaling controls BMP4 expression and with canonical Wnt signaling, regulates the posteriorization of the primitive streak, development of the mesoderm, development of early hematopoetic stem cells, and the property of self renewal in adult hematopoiesis. This study investigated the extent that microgravity alters expression of these spatially orienting proteins of BMP4, Nodal, Wnt, and SMAD2 thus influencing the anemia, thrombocytopenia, and immune alteration associated with space flight. Method: The Gene Expression Omnibus Database (GEO) of the National Institutes of Health was accessed to define RNA expression of Nodal, SMAD2, Wnt and BMP4 in hematopoetic cells in microgravity. Initial queries for “Low Gravity” studies resulted in 565 investigations within the GEO Omnibus. Of the 565 studies, the GSE136939, GSE101102, and the GSE101309 datasets were explored which assessed the lymphoid and macrophage cell lines TK6, U937, and Jurkat. RNA expression with normal and microgravity environments were compared. In the U937 cells hypergravity environments were also studied. Nodal, Lefty, Wnt, BMP4, as well as the NODAL signaling cascade proteins of SMAD 1/5, SMAD2, SMAD3, and the inhibitory SMAD 7. Affymetrix Expression Arrays were utilized for the TK^ and Jurkat cells assays. The U937 cell lines were assayed with NimbleGen Human Gene Assay Arrays. Results: Significant decreases in BMP4 expression were seen in microgravity environments (P value,