Omega Point · Lab
Hypotheses
Every hypothesis every run has written, newest run first. Each row says where it is: being named, waiting for the rest of its run, checked for duplicates, approved and being explained, published. A duplicate names the earlier hypothesis it restates. A published row links to its public page; nothing else is a link.
Run: pipeline-2d7e735a19c5the run
| Hypothesis▲ | Question asked▲ | Date▼ | Lens▲ | Status▲ |
|---|---|---|---|---|
| Ageing installs the anti-fibrotic switch that spiny mice are born with IH_Q_L3_M_G1_1_01 · #0 Constant itaconate in aged niche macrophages blocks TET2 and methylates the IRF4 site at the TGFB1 enhancer, so pro-resolution signalling stops driving scar formation. The gap between humans and the regenerating spiny mouse Acomys would then be a difference of age, not of species. Explains the gap: Does SPM-driven M2 polarization in human niche macrophages increase or decrease TGF-β1 secretion, given that the Acomys IRF4-half-site CpG methylation decoupling pro-resolution from fibrosis is absent in humans? Clash gap | How to rejuvenate the stem cell niche? | 2026-09-13 23:27 | Information and sensing | Published live 2026-09-14 Published · poster live |
| The fibrosis signal is stopped by the hyaluronan mesh, not by the macrophage IH_Q_L3_M_G1_1_02 · #1 TGF-β1, the growth factor that turns fibroblasts into scar-forming cells, never reaches them while the dense ultra-high-molecular-weight hyaluronan coat around the cell is intact. What changes with age is the size of that mesh, not how much the macrophage secretes. Explains the gap: Does SPM-driven M2 polarization in human niche macrophages increase or decrease TGF-β1 secretion, given that the Acomys IRF4-half-site CpG methylation decoupling pro-resolution from fibrosis is absent in humans? Clash gap | How to rejuvenate the stem cell niche? | 2026-09-13 23:27 | Structure and topology | Published live 2026-09-14 Published · poster live |
| The link between resolving inflammation and fibrosis is an artefact of culture plastic IH_Q_L3_M_G1_1_03 · #2 Culture plastic is a million times stiffer than tissue, and that stiffness alone pushes the mechanical sensor YAP into the nucleus, where it switches on TGFB1 beside the healing programme. On tissue-soft gels the coupling should vanish, which would mean it never existed in a living niche in either species. Explains the gap: Does SPM-driven M2 polarization in human niche macrophages increase or decrease TGF-β1 secretion, given that the Acomys IRF4-half-site CpG methylation decoupling pro-resolution from fibrosis is absent in humans? Clash gap | How to rejuvenate the stem cell niche? | 2026-09-13 23:27 | phenomenon does not exist | Published live 2026-09-14 Published · poster live |
| NAD+ decides whether a healing macrophage also turns fibrotic IH_Q_L3_M_G1_1_04 · #3 While the metabolic cofactor NAD+ is plentiful, the enzyme SIRT6 holds the TGFB1 promoter closed and a macrophage can resolve inflammation without driving scar. Aged macrophages lose most of their NAD+, the brake comes off, and restoring it should put the brake back. Explains the gap: Does SPM-driven M2 polarization in human niche macrophages increase or decrease TGF-β1 secretion, given that the Acomys IRF4-half-site CpG methylation decoupling pro-resolution from fibrosis is absent in humans? Clash gap | How to rejuvenate the stem cell niche? | 2026-09-13 23:27 | Resource and energy | Published live 2026-09-14 Published · poster live |
| Resolvins may drive fibrosis in aged cells rather than resolve it IH_Q_L3_M_G1_1_05 · #4 A worn-out FPR2 receptor does not merely respond weakly to resolvins. It switches them to a β-arrestin-biased output that reinforces TGF-β1 production, which would make supplementing aged tissue with these pro-resolution molecules actively harmful rather than simply ineffective. Explains the gap: Does SPM-driven M2 polarization in human niche macrophages increase or decrease TGF-β1 secretion, given that the Acomys IRF4-half-site CpG methylation decoupling pro-resolution from fibrosis is absent in humans? Clash gap | How to rejuvenate the stem cell niche? | 2026-09-13 23:27 | System and environment | Published live 2026-09-14 Published · poster live |