Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-5-30
pubmed:abstractText
The current belief is that the epidermal sebaceous gland (SG) is maintained by unipotent stem cells that are replenished by multipotent stem cells in the hair follicle (HF) bulge. However, sebocytes can be induced by c-Myc (Myc) activation in interfollicular epidermis (IFE), suggesting the existence of bipotential stem cells. We found that every SZ95 immortalized human sebocyte that underwent clonal growth in culture generated progeny that differentiated into both sebocytes and cells expressing involucrin and cornifin, markers of IFE and HF inner root sheath differentiation. The ability to generate involucrin positive cells was also observed in a new human sebocyte line, Seb-E6E7. SZ95 xenografts differentiated into SG and IFE but not HF. SZ95 cells that expressed involucrin had reduced Myc levels; however, this did not correlate with increased expression of the Myc repressor Blimp1, and Blimp1 expression did not distinguish cells undergoing SG, IFE, or HF differentiation in vivo. Overexpression of Myc stimulated sebocyte differentiation, whereas overexpression of beta-catenin stimulated involucrin and cornifin expression. In transgenic mice simultaneous activation of Myc and beta-catenin revealed mutual antagonism: Myc blocked ectopic HF formation and beta-catenin reduced SG differentiation. Overexpression of the Myc target gene Indian hedgehog did not promote sebocyte differentiation in culture and cyclopamine treatment, while reducing proliferation, did not block Myc induced sebocyte differentiation in vivo. Our studies provide evidence for a bipotential epidermal stem cell population in an in vitro model of human epidermal lineage selection and highlight the importance of Myc as a regulator of sebocyte differentiation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1549-4918
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1241-52
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18308950-Animals, pubmed-meshheading:18308950-Biological Markers, pubmed-meshheading:18308950-Cell Differentiation, pubmed-meshheading:18308950-Cell Line, pubmed-meshheading:18308950-Cell Line, Transformed, pubmed-meshheading:18308950-Cell Lineage, pubmed-meshheading:18308950-Cornified Envelope Proline-Rich Proteins, pubmed-meshheading:18308950-Epidermis, pubmed-meshheading:18308950-Hedgehog Proteins, pubmed-meshheading:18308950-Humans, pubmed-meshheading:18308950-Membrane Proteins, pubmed-meshheading:18308950-Mice, pubmed-meshheading:18308950-Mice, Inbred BALB C, pubmed-meshheading:18308950-Protein Precursors, pubmed-meshheading:18308950-Proto-Oncogene Proteins c-myc, pubmed-meshheading:18308950-Repressor Proteins, pubmed-meshheading:18308950-Sebaceous Glands, pubmed-meshheading:18308950-Stem Cells, pubmed-meshheading:18308950-Transplantation, Heterologous, pubmed-meshheading:18308950-beta Catenin
pubmed:year
2008
pubmed:articleTitle
Characterization of bipotential epidermal progenitors derived from human sebaceous gland: contrasting roles of c-Myc and beta-catenin.
pubmed:affiliation
Massachusetts General Hospital, Center for Regenerative Medicine, Boston, Massachusetts, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural