title: Notch-Dependent Pituitary SOX2(+) Stem Cells Exhibit a Timed Functional Extinction in Regulation of the Postnatal Gland.
abstract: Although SOX2(+) stem cells are present in the postnatal pituitary gland, how they are regulated molecularly and whether they are required for pituitary functions remain unresolved questions. Using a conditional knockout animal model, here we demonstrate that ablation of the canonical Notch signaling in the embryonic pituitary gland leads to progressive depletion of the SOX2(+) stem cells and hypoplastic gland. Furthermore, we show that the SOX2(+) stem cells initially play a significant role in contributing to postnatal pituitary gland expansion by self-renewal and differentiating into distinct lineages in the immediate postnatal period. However, we found that within several weeks postpartum, the SOX2(+) stem cells switch to an essentially dormant state and are no longer required for homeostasis/tissue adaptation. Our results present a dynamic tissue homeostatic model in which stem cells provide an initial contribution to the growth of the neonatal pituitary gland, whereas the mature gland can be maintained in a stem cell-independent fashion.
authors.affiliation: Howard Hughes Medical Institute, Department and School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA. Electronic address: xzhu@salk.edu.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Howard Hughes Medical Institute, Department and School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Tollkuhn
authors.affiliation: Howard Hughes Medical Institute, Department and School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Havilah
authors.initials: H
authors.lastname: Taylor
authors.affiliation: Howard Hughes Medical Institute, Department and School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA. Electronic address: mrosenfeld@ucsd.edu.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenfeld
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008822:Mice, Transgenic; D009154:Mutation; D010902:Pituitary Gland / Q000166:cytology* / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C102134:Prophet of Pit-1 protein; D051880:Receptors, Notch; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse