Transflammation: How Innate Immune Activation and Free Radicals Drive Nuclear Reprogramming.
SIGNIFICANCE
Yamanaka and colleagues galvanized the field of stem cell biology and regenerative medicine by their generation of induced pluripotent stem cells. Evidence is emerging that activation of innate immune signaling is critical for efficient reprogramming to pluripotency and for the nuclear reprogramming occurring in transdifferentiation. Recent Advances: We have shown that innate immune signaling triggers a global change in the expression of epigenetic modifiers to enhance DNA accessibility. In this state of epigenetic plasticity, overexpression of lineage determination factors, and/or environmental cues and paracrine factors, can induce pluripotency, or can direct transdifferentiation to another somatic cell lineage. Accumulating evidence reveals that innate immune activation triggers the generation of reactive oxygen species and reactive nitrogen species, and that these free radicals are required for nuclear reprogramming to pluripotency or for transdifferentiation.


CRITICAL ISSUES
We have discovered a limb of innate immune signaling that regulates DNA accessibility, in part, by the action of free radicals to induce post-translational modification of epigenetic modifiers.


FUTURE DIRECTIONS
It is of scientific interest and clinical relevance to understand the mechanisms by which free radicals influence epigenetic plasticity, and how these mechanisms may be therapeutically modulated. Antioxid. Redox Signal. 00, 000-000.
['Meng|Shu|S|', 'Chanda|Palas|P|', 'Thandavarayan|Rajarajan A|RA|', 'Cooke|John P|JP|']
D000818:Animals D054338:Cell Transdifferentiation D065150:Cellular Reprogramming D053595:Embryonic Stem Cells D044127:Epigenesis, Genetic D005609:Free Radicals D006801:Humans D007113:Immunity, Innate D057026:Induced Pluripotent Stem Cells D051379:Mice D052247:Nitric Oxide Synthase Type II D017382:Reactive Oxygen Species D015398:Signal Transduction
transflammation innate immunity nuclear reprogramming induced pluripotent stem cells nitric oxide