title: Atypical PKC-iota Controls Stem Cell Expansion via Regulation of the Notch Pathway.
abstract: The number of stem/progenitor cells available can profoundly impact tissue homeostasis and the response to injury or disease. Here, we propose that an atypical PKC, Prkci, is a key player in regulating the switch from an expansion to a differentiation/maintenance phase via regulation of Notch, thus linking the polarity pathway with the control of stem cell self-renewal. Prkci is known to influence symmetric cell division in invertebrates; however a definitive role in mammals has not yet emerged. Using a genetic approach, we find that loss of Prkci results in a marked increase in the number of various stem/progenitor cells. The mechanism used likely involves inactivation and symmetric localization of NUMB, leading to the activation of NOTCH1 and its downstream effectors. Inhibition of atypical PKCs may be useful for boosting the production of pluripotent stem cells, multipotent stem cells, or possibly even primordial germ cells by promoting the stem cell/progenitor fate.
authors.affiliation: Broad CIRM Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, 1425 San Pablo St., Los Angeles, CA 90033, USA.
authors.forename: In Kyoung
authors.initials: IK
authors.lastname: Mah
authors.affiliation: Department of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Soloff
authors.affiliation: Department of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hedrick
authors.affiliation: Broad CIRM Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, 1425 San Pablo St., Los Angeles, CA 90033, USA. Electronic address: fmariani@usc.edu.
authors.forename: Francesca V
authors.initials: FV
authors.lastname: Mariani
mesh_terms: D000818:Animals; D000066673:Cell Self Renewal; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000378:metabolism*; D000099293:Protein Kinase C-lambda
chemical_list: D007527:Isoenzymes; D011493:Protein Kinase C; D051881:Receptor, Notch1; D000099293:Protein Kinase C-lambda; C497762:Notch1 protein, mouse