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Ion Channels in Human Pluripotent Stem Cells and Their Neural Derivatives
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Ritika Raghavan, Robert Juniewicz, Maharaib Syed, Michael Lin, Peng Jiang
Human iPSCs and ESCs are morphologically identical and largely share electrophysiological properties at the pluripotent state. They appear to both be electrophysiologically homogenous, with both cell types exhibiting depolarization-activated delayed rectifier K+ currents (IKDR) and 4-aminopyradine (4-AP) sensitive currents but not voltage-gated sodium channel currents (INa), voltage-gated calcium currents (ICa)and Ca2+ activated K+ currents (IKCa) (33). At transcriptomic level, the expression of transcripts encoding ion channels could not be distinguished in hESCs and hiPSCs. KCNQ2 transcript has the highest expression in both hiPSCs and hESCs, which encodes the non-inactivating, slowly deactivating M-current (33,34). Also expressed in both hiPSC and hESCs are CNC4, which encodes delayed rectifier voltage-gated potassium channels (Kv3.4), and KCNS3 which encodes the silent modulatory α-subunit of IKDR channels (33). The detection of IKDR was at a high current density (47.5 ± 7.9 pA/pF at +40 mV) for both hESCs and hiPSCs and these IKDR are believed to have a role in proliferation (33,34). Tetraethylammonium (TEA), a blocker of IKDR, dose-dependently inhibited hESC proliferation with an EC50 of 11.6 ± 2.0mM and hiPSC proliferation with an EC50 of 7.8 ± 1.2 mM (33,34).
RNA-Seq investigation and in vivo study the effect of strontium ranelate on ovariectomized rat via the involvement of ROCK1
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Xiaojing Guo, Silong Wei, Mengmeng Lu, Zhengwei Shao, Jiayu Lu, Lunguo Xia, Kaili Lin, Derong Zou
Although our previous study has reported that SrR could promote osteogenic differentiation and angiogenic factor expression of OVX-rBMSCs [29], the underlying mechanisms involved have not been fully understood. First, we compared the gene-expression difference between control OVX-rBMSCs (n = 3) and OVX-rBMSCs with SrR treatment (n = 3) using RNA-sequencing analysis. We identified 90 out of 12,330 transcripts exhibited distinct expression patterns between control and SrR (Table 2). About 41 of the transcripts were increased in OVX-rBMSCs with SrR treatment. Among these transcripts, the five highest increase were Exoc7 (17.11-fold), Dhrs9 (14.46-fold), Cyp4f37 (10.86-fold), Ly6g5b (7.15-fold) and Kcns3 (7.07-fold). On the other hand, transcripts showed the five highest decrease were Nrg4 (0.12-fold), LOC100911576 (0.15-fold), Mir1956 (0.15-fold), Cecr2 (0.17-fold) and Brms1 (0.21-fold). Interestingly, ROCK1 which has been shown to promote osteogenesis was also found increased expression in OVX-rBMSCs with SrR treatment compared with the control OVX-rBMSCs (1.55-fold). To further determine the signalling pathways that were altered in OVX-rBMSCs, GSEA was performed. We found that ROCK1 was involved in two signalling pathways, including TGF-β signalling pathway (p = .015) and chemokine signalling pathway (p = .024) (Figure 1(a,b)), and the GSEA details in OVX-rBMSCs with SrR treatment and the control OVX-rBMSCs involving TGF-β signalling pathway (Figure 1(c)) and chemokine signalling pathway (Figure 1(d)) were also shown. These findings suggested that ROCK1 may associate with the effects of SrR on the osteogenic differentiation of OVX-rBMSCs and the role of ROCK1 is therefore further confirmed.