Wnt3a-coated beads can induce asymmetric divisions of mouse embryonic stem cells (mESCs), resulting in one self-renewed mESC and one differentiating epiblast stem cell. This provides an opportunity for studying histone inheritance pattern at a single-cell resolution in cell culture. Here, we report that mESCs with Wnt3abead induction display nonoverlapping preexisting (old) versus newly synthesized (new) histone H3 patterns, but mESCs without Wnt3a beads have largely overlapping patterns. Furthermore, H4K20me2/3, an old histone-enriched modification, displays a higher instance of asymmetric distribution on chromatin fibers from Wnt3a-induced mESCs than those from non-induced mESCs. These locally distinct distributions between old and new histones have both cellular specificity in Wnt3a-induced mESCs and molecular specificity for histones H3 and H4. Given that post-translational modifications at H3 and H4 carry the major histone modifications, our findings provide a mammalian cell culture system to study histone inheritance for maintaining stem cell fate and for resetting it during differentiation.
Our findings suggest differences in brain functional connectivity between smokers and non-smokers. This study sheds new insights into the neural mechanisms of tobacco dependence.
CTP synthase (CTPS) is an important metabolic enzyme that catalyzes the rate-limiting reaction of de novo synthesis of the nucleotide CTP. Since 2010, a series of studies have demonstrated that CTPS can form filamentous structures termed cytoophidia in bacteria and eukaryotes. However, it remains unknown whether cytoophidia exist in archaea, the third domain of life. UsingHaloarcula hispanica as a model system, here we demonstrate that CTPS forms distinct intracellular compartments in archaeal cells.Under stimulated emission depletion (STED) microscopy, we find that some HhCTPS compartments have elongated filamentous structures, resembling cytoophidia in bacteria and eukaryotes.When Haloarcula cells are cultured in low-salt medium, the occurrence of cytoophidia increases dramatically. Moreover, overexpression of CTPS or glutamine analog treatment promotes cytoophidium assembly in H. hispanica. Our study reveals that CTPS forms cytoophidia in all three domains of life, suggesting that this is an ancient property of CTPS.
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