Notch-Dependent Pituitary SOX2(+) Stem Cells Exhibit a Timed Functional Extinction in Regulation of the Postnatal Gland

Stem Cell Reports. 2015 Dec 8;5(6):1196-1209. doi: 10.1016/j.stemcr.2015.11.001.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Female
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Mice, Transgenic
  • Mutation
  • Pituitary Gland / cytology*
  • Pituitary Gland / metabolism
  • Receptors, Notch / metabolism*
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism*
  • Signal Transduction*
  • Stem Cells / cytology*
  • Stem Cells / metabolism

Substances

  • Homeodomain Proteins
  • Prophet of Pit-1 protein
  • Receptors, Notch
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse