Molecular biology of the stress response in the early embryo and its stem cells.

摘要: Stress is normal during early embryogenesis and transient, elevated stress commonplace. in the milieu of peri-implantation embryo a summation maternal hormones, other elements milieu, that signal preparedness for development implantation. Examples discussed here are leptin, adrenaline, cortisol, progesterone. These hormones nutritional status provide energy, but also diverts embryonic energy from an optimal developmental trajectory. communicate endocrine effects local although signaling mechanisms not well understood. Other vivo stresses affect such as infection inflammation, hypoxia, environmental toxins benzopyrene, dioxin, or metals, heat shock, hyperosmotic due to dehydration diabetes. In vitro, include shear handling, improper culture media oxygen levels, cryopreservation, manipulations introduce sperm mitochondria. We define any stimulus slows stem cell accumulation diminishes ability cells produce sufficient parenchymal products upon differentiation. Thus deflects downwards trajectories development, growth Typically inversely proportional proliferative rates, can be induction differentiation embryo. When modeling it most interesting ‘runting model’ where exposures slow do create excessive apoptosis morbidity. Windows sensitivity may occur when major new programs require large amounts exacerbated if flow decreases removes responses. windows correspond zygotic genome activation, mRNA program initiated at compaction, ion pumping required cavitation, first lineages, integration with uterine environment implantation, rapid proliferation cells, production certain lineages which highest sensitive mitochondrial inhibition. response insure placenta survive lower exposures, organism survives through compensatory prioritized differentiation, higher exposures. servomechanisms small set enzymes 500 protein kinases kinome; part coding hierarchically regulate activity proteins enzymes. Important mediate embryos their SAPK, p38MAPK, AMPK, PI3K, Akt, MEK1/2, MEKK4, PKA, IRE1 PERK. have cytosolic function survival low nuclear modifying transcription factor Some factors (TFs) important JunC, JunB, MAPKAPs, ATF4, XBP1, Oct1, Oct4, HIFs, Nrf2/KEAP, NFKB, MT1, Nfat5, HSF1/2 potency-maintaining Id2, Cdx2, Eomes, Sox2, Nanog, Rex1, Oct4. Clearly number substrates TFs numbers genes. The interaction its continuing central focus research. vitro regulation by leads reprogramming accumulation. Since more differentiated product produced fewer process compensates cells. Coupled stress-induced tendency prioritize increasing essential lineage decreasing later lineages. stress-specific, shared homeostatic cellular organismal responses