title: Role of STIM1 in survival and neural differentiation of mouse embryonic stem cells independent of Orai1-mediated Ca2+ entry.
abstract: Store-operated Ca(2+) entry (SOCE) is an important Ca(2+) influx pathway in non-excitable cells. STIM1, an ER Ca(2+) sensor, and Orai1, a plasma membrane Ca(2+) selective channel, are the two essential components of the Ca(2+) release activated channel (CRAC) responsible for SOCE activity. Here we explored the role of STIM1 and Orai1 in neural differentiation of mouse embryonic stem (ES) cells. We found that STIM1 and Orai1 were expressed and functionally active in ES cells, and expressions of STIM1 and Orai1 were dynamically regulated during neural differentiation of mouse ES cells. STIM1 knockdown inhibited the differentiation of mouse ES cells into neural progenitors, neurons, and astrocytes. In addition, STIM1 knockdown caused severe cell death and markedly suppressed the proliferation of neural progenitors. Surprisingly, Orai1 knockdown had little effect on neural differentiation of mouse ES cells, but the neurons derived from Orai1 knockdown ES cells, like those from STIM1 knockdown cells, had defective SOCE. Taken together, our data indicate that STIM1 is involved in both early neural differentiation of ES cells and survival of early differentiated ES cells independent of Orai1-mediated SOCE.
authors.affiliation: Department of Physiology, University of Hong Kong, Hong Kong, China.
authors.forename: Baixia
authors.initials: B
authors.lastname: Hao
authors.affiliation: Department of Physiology, University of Hong Kong, Hong Kong, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Physiology, University of Hong Kong, Hong Kong, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Physiology, University of Hong Kong, Hong Kong, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Physiology, University of Hong Kong, Hong Kong, China.
authors.forename: King-Ho
authors.initials: KH
authors.lastname: Cheung
authors.affiliation: Department of Physiology, University of Hong Kong, Hong Kong, China. Electronic address: jbyue@me.com.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Yue
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D051379:Mice; D000071740:ORAI1 Protein; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D000071740:ORAI1 Protein; C520430:Orai1 protein, mouse; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D002118:Calcium