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- Rutter, Lindsay, et al.
(författare)
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A New Era for Space Life Science : International Standards for Space Omics Processing
- 2020
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Ingår i: PATTERNS. - : Elsevier BV. - 2666-3899. ; 1:9, s. 100148-
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Forskningsöversikt (refereegranskat)abstract
- Space agencies have announced plans for human missions to the Moon to prepare for Mars. However, the space environment presents stressors that include radiation, microgravity, and isolation. Understanding how these factors affect biology is crucial for safe and effective crewed space exploration. There is a need to develop countermeasures, to adapt plants and microbes for nutrient sources and bioregenerative life support, and to limit pathogen infection. Scientists across the world are conducting space omics experiments onmodel organisms and, more recently, on humans. Optimal extraction of actionable scientific discoveries fromtheseprecious datasets will only occur at the collective level with improved standardization. To address this shortcoming, we established ISSOP (International Standards for Space Omics Processing), an international consortium of scientists who aim to enhance standard guidelines between space biologists at a global level. Here we introduce our consortium and share past lessons learned and future challenges related to spaceflight omics.
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| 2. |
- Suzuki, Toshiyasu, et al.
(författare)
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b-Catenin Drives Butyrophilin-like Molecule Loss and gd T-cell Exclusion in Colon Cancer
- 2023
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Ingår i: CANCER IMMUNOLOGY RESEARCH. - : AMER ASSOC CANCER RESEARCH. - 2326-6066. ; 11:8, s. 1137-1155
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Tidskriftsartikel (refereegranskat)abstract
- Intraepithelial lymphocytes (IEL) expressing y8 T-cell receptors (y8TCR) play key roles in elimination of colon cancer. However, the precise mechanisms by which progressing cancer cells evade immu-nosurveillance by these innate T cells are unknown. Here, we investigated how loss of the Apc tumor suppressor in gut tissue could enable nascent cancer cells to escape immunosurveillance by cytotoxic y8IELs. In contrast with healthy intestinal or colonic tissue, we found that y8IELs were largely absent from the micro-environment of both mouse and human tumors, and that butyr-ophilin-like (BTNL) molecules, which can critically regulate y8IEL through direct y8TCR interactions, were also downregulated in tumors. We then demonstrated that 13-catenin activation through loss of Apc rapidly suppressed expression of the mRNA encoding the HNF4A and HNF4G transcription factors, preventing their binding to promoter regions of Btnl genes. Reexpression of BTNL1 and BTNL6 in cancer cells increased y8IEL survival and activation in coculture assays but failed to augment their cancer-killing ability in vitro or their recruitment to orthotopic tumors. However, inhibition of 13-catenin signaling via genetic deletion of Bcl9/Bcl9L in either Apc-deficient or mutant 13-catenin mouse models restored Hnf4a, Hnf4g, and Btnl gene expression and y8 T-cell infiltration into tumors. These observations highlight an immune-evasion mechanism specific to WNT-driven colon cancer cells that disrupts y8IEL immunosurveillance and furthers cancer progression.
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