title: CD271 mediates stem cells to early progeny transition in human epidermis.
abstract: CD271 is the low-affinity neurotrophin (p75NTR) receptor that belongs to the tumor necrosis factor receptor superfamily. Because in human epidermis, CD271 is predominantly expressed in transit-amplifying (TA) cells, we evaluated the role of this receptor in keratinocyte differentiation and in the transition from keratinocyte stem cells (KSCs) to progeny. Calcium induced an upregulation of CD271 in subconfluent keratinocytes, which was prevented by CD271 small interfering RNA. Furthermore, CD271 overexpression provoked the switch of KSCs to TA cells, whereas silencing CD271 induced TA cells to revert to a KSC phenotype, as shown by the expression of β1-integrin and by the increased clonogenic ability. CD271(+) keratinocytes sorted from freshly isolated TA cells expressed more survivin and keratin 15 (K15) compared with CD271(-) cells and displayed a higher proliferative capacity. Early differentiation markers and K15 were more expressed in the skin equivalent generated from CD271(+) TA than from those derived from CD271(-) TA cells. By contrast, late differentiation markers were more expressed in skin equivalents from CD271(-) than in reconstructs from CD271(+) TA cells. Finally, skin equivalents originated from CD271(-) TA cells displayed a psoriatic phenotype. These results indicate that CD271 is critical for keratinocyte differentiation and regulates the transition from KSCs to TA cells.
authors.affiliation: Laboratory of Cutaneous Biology, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Truzzi
authors.affiliation: Laboratory of Cutaneous Biology, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Saltari
authors.affiliation: Laboratory of Cutaneous Biology, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Palazzo
authors.affiliation: Laboratory of Cutaneous Biology, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Lotti
authors.affiliation: Laboratory of Cutaneous Biology, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Petrachi
authors.affiliation: Laboratory of Cutaneous Biology, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Katiuscia
authors.initials: K
authors.lastname: Dallaglio
authors.affiliation: Department of Life Science, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gemelli
authors.affiliation: Laboratory of Cell Biology and Advanced Cancer Therapies, Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Grisendi
authors.affiliation: Laboratory of Cell Biology and Advanced Cancer Therapies, Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Dominici
authors.affiliation: Laboratory of Cutaneous Biology, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: carlo.pincelli@unimore.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Pincelli
authors.affiliation: Laboratory of Cutaneous Biology, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Marconi
mesh_terms: D002118:Calcium / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D053569:Keratin-15 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011565:Psoriasis / Q000473:pathology; D034741:RNA, Small Interfering / Q000494:pharmacology; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D053569:Keratin-15; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D017475:Receptors, Nerve Growth Factor; D000077022:Survivin; D002118:Calcium