Project description:Progenitor/stem cell populations of the aorta have been poorly characterized and their self-renewal factors unknown. In this report, we demonstrate that sphere forming progenitor/stem cells, here within termed aortic neurospheres (ANS), can be cultivated from the aorta that are similar to skin-derived precursors (SKPs). Extensive mRNA transcript profiling revealed that ANS abundantly expressed the Inhibin βA transcript, of which the secreted protein dominantly formed the Inhibin βA-βA complex, or Activin A, in the proliferation medium. Co-localization of Activin A, Nestin and Sox2 was observed in the adventitial and peri-adventitial regions of the aorta, indicative of a progenitor/stem cell niche in vivo. Blockade of Activin A signaling, through the neutralization of the Type II Activin receptors ActRIIA and ActRIIB, resulted in the asymmetric differentiation, and epithelial-to-mesenchymal transition of the ANS, respectively. When treated with the latter neutralizing antibody, translocation of the ActRIIB receptor to the nucleus was observed in cells on the periphery of the sphere. Examination of the ActRIIB protein sequence showed the presence of a putative nuclear localization signal of the PY family that was conserved across species. The results from this study demonstrate that Activin A is a self-renewal factor required for maintaining ANS progenitor/stem cell identity and multipotency.
Project description:Progenitor/stem cell populations of the aorta have been poorly characterized and their self-renewal factors unknown. In this report, we demonstrate that sphere forming progenitor/stem cells, here within termed aortic neurospheres (ANS), can be cultivated from the aorta that are similar to skin-derived precursors (SKPs). Extensive mRNA transcript profiling revealed that ANS abundantly expressed the Inhibin βA transcript, of which the secreted protein dominantly formed the Inhibin βA-βA complex, or Activin A, in the proliferation medium. Co-localization of Activin A, Nestin and Sox2 was observed in the adventitial and peri-adventitial regions of the aorta, indicative of a progenitor/stem cell niche in vivo. Blockade of Activin A signaling, through the neutralization of the Type II Activin receptors ActRIIA and ActRIIB, resulted in the asymmetric differentiation, and epithelial-to-mesenchymal transition of the ANS, respectively. When treated with the latter neutralizing antibody, translocation of the ActRIIB receptor to the nucleus was observed in cells on the periphery of the sphere. Examination of the ActRIIB protein sequence showed the presence of a putative nuclear localization signal of the PY family that was conserved across species. The results from this study demonstrate that Activin A is a self-renewal factor required for maintaining ANS progenitor/stem cell identity and multipotency.
Project description:Progenitor/stem cell populations of the aorta have been poorly characterized and their self-renewal factors unknown. In this report, we demonstrate that sphere forming progenitor/stem cells, here within termed aortic neurospheres (ANS), can be cultivated from the aorta that are similar to skin-derived precursors (SKPs). Extensive mRNA transcript profiling revealed that ANS abundantly expressed the Inhibin βA transcript, of which the secreted protein dominantly formed the Inhibin βA-βA complex, or Activin A, in the proliferation medium. Co-localization of Activin A, Nestin and Sox2 was observed in the adventitial and peri-adventitial regions of the aorta, indicative of a progenitor/stem cell niche in vivo. Blockade of Activin A signaling, through the neutralization of the Type II Activin receptors ActRIIA and ActRIIB, resulted in the asymmetric differentiation, and epithelial-to-mesenchymal transition of the ANS, respectively. When treated with the latter neutralizing antibody, translocation of the ActRIIB receptor to the nucleus was observed in cells on the periphery of the sphere. Examination of the ActRIIB protein sequence showed the presence of a putative nuclear localization signal of the PY family that was conserved across species. The results from this study demonstrate that Activin A is a self-renewal factor required for maintaining ANS progenitor/stem cell identity and multipotency.
Project description:This assay assessed genome-wide chromatin occupancy by transcription factor PBX1, alongside activity-associated histone mark H3K27ac in a primary adult neurogenic population (adult neurospheres, aNS, isolated from the ventricular-subventricular zone, V-SVZ) capable of differentiating into all neural lineages.
Project description:We found the impaired renal function accompanied with severe cardiac dysfunction in mice co-treated with angiotensin II, nephrectomy and salt (ANS), and identified the increased level of plasma histamine in ANS-treated mice. Interestingly, pro-inflammatory genes were increased in kidneys of ANS-treated animals, which were down-regulated by histamine H3 receptor (H3R) agonist. Purpose: To evaluate the molecular mechanisms underlying the effect of the H3R agonist on the ANS-induced renal and cardiac inflammation, we performed a comprehensive analysis of ANS-mediated gene expression changes with/without H3R agonist in kidneys and hearts using RNA sequencing (RNA-Seq). Results: To investigate differentially expressed genes (false discovery rate (FDR) p<0.05, fold change >2) among three groups, we performed pairwise comparisons of RNA-Seq data using the CLC Genomics Workbench software. In comparison with the control of kidney group, 1,283 (1,010 up- and 273 down-regulated) unique genes were significantly changed in the ANS-treated group. Meanwhile, the data set of ANS-treated kidneys with H3R agonist revealed significant changes in 234 (65 up- and 169 down-regulated) genes as compared with the control groups. In case of hearts, the ANS-treated group revealed that 85 (66 up- and 19 down-regulated) unique genes were significantly changed compared to the control groups. Furthermore, in comparison with the ANS-treated with H3R agonist group, one up-regulated gene was significantly changed in the ANS-treated group.