title: Cytokeratin15-positive basal epithelial cells targeted in graft-versus-host disease express a constitutive antiapoptotic phenotype.
abstract: The normal gene expression profile of rete-tip keratinocytes targeted in human graft-versus-host disease (GVHD) remains unexplored. Murine lingual epithelium, unlike murine skin, consists of a basal layer that resembles human cutaneous rete ridges and harbors rete tip-associated cells that express cytokeratin 15 (K15), a marker for epithelial stem cells. Target cell apoptosis in murine GVHD preferentially involves subpopulations of basal cells that (1) reside at tips of lingual rete ridge-like prominences (RLPs), (2) constitutively express K15 protein, (3) express the proapoptotic protein Bax early in disease progression, and (4) coincide spatially with putative epithelial stem cells. Here, we show by real-time reverse transcription-PCR that immunohistochemistry-guided laser-captured K15-positive (K15+) murine basal cells constitutively express quantitatively higher mRNA levels for K15 but lower mRNA levels of Bax than do K15- basal cells, consistent with the presumed stem cell nature of K15+ basal cells. Moreover, apoptosis gene array screening of K15+ microdissected basal cells demonstrated a dominant trend toward the preferential expression of genes associated with protection from apoptosis. Accordingly, genes that regulate apoptotic vulnerability are differentially expressed in basal layer subpopulations distinguishable by K15 expression.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhan
authors.forename: Sabina
authors.initials: S
authors.lastname: Signoretti
authors.forename: Diana
authors.initials: D
authors.lastname: Whitaker-Menezes
authors.forename: Thea M
authors.initials: TM
authors.lastname: Friedman
authors.forename: Robert
authors.initials: R
authors.lastname: Korngold
authors.forename: George F
authors.initials: GF
authors.lastname: Murphy
mesh_terms: D000818:Animals; D017209:Apoptosis; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006086:Graft vs Host Disease / Q000378:metabolism* / Q000473:pathology; D053569:Keratin-15 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015603:Keratinocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000032:analysis / Q000235:genetics
chemical_list: D053569:Keratin-15; D051028:bcl-2-Associated X Protein