title: Highly upregulated Lhx2 in the Foxn1-/- nude mouse phenotype reflects a dysregulated and expanded epidermal stem cell niche.
abstract: Hair cycling is a prime example of stem cell dependent tissue regeneration and replenishment, and its regulatory mechanisms remain poorly understood. In the present study, we evaluated the effect of a blockage in terminal keratinocytic lineage differentiation in the Foxn1(-/-) nude phenotype on the epithelial progeny. Most notably we found a constitutive upregulation of LIM homeobox protein 2 (Lhx2), a marker gene of epithelial stem cellness indispensible for hair cycle progression. However, histological evidence along with an erratic, acyclic rise of otherwise suppressed CyclinD1 levels along with several key markers of keratinocyte lineage differentiation indicate a frustrated expansion of epithelial stem cell niches in skin. In addition, CD49f/CD34/CD200-based profiling demonstrated highly significant shifts in subpopulations of epithelial progeny. Intriguingly this appeared to include the expansion of Oct4+ stem cells in dermal fractions of skin isolates in the Foxn1 knock-out opposed to wild type. Overall our findings indicate that the Foxn1(-/-) phenotype has a strong impact on epithelial progeny and thus offers a promising model to study maintenance and regulation of stem cell niches within skin not feasible in other in vitro or in vivo models.
authors.affiliation: Center for Engineering in Medicine, Shriners Hospitals for Children and Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. bohrs@partners.org
authors.forename: Stefan
authors.initials: S
authors.lastname: Bohr
authors.forename: Suraj J
authors.initials: SJ
authors.lastname: Patel
authors.forename: Radovan
authors.initials: R
authors.lastname: Vasko
authors.forename: Keyue
authors.initials: K
authors.lastname: Shen
authors.forename: Guofeng
authors.initials: G
authors.lastname: Huang
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
authors.forename: Francois
authors.initials: F
authors.lastname: Berthiaume
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000166:cytology*; D055153:Stem Cell Niche / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; C489783:LHX2 protein, human; D060850:LIM-Homeodomain Proteins; C489784:Lhx2 protein, mouse; D050814:Octamer Transcription Factor-3; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors; C090140:Whn protein; D019938:Cyclin D1