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.

p75 Neurotrophin Receptor in the Skin: Beyond Its Neurotrophic Function

“…In addition, p75 NTR -positive TA cells display a higher proliferative capacity and a better colony forming efficiency, as compared to p75 NTR -negative cells. Finally, human reconstructed epidermis derived from p75 NTR -positive TA cells express markers of early differentiation (73). This indicates that p75 NTR identifies a population of early TA cells.…”

“…In fact, silencing p75 NTR prevents calcium-induced keratinocyte differentiation and converts TA cells into a KSC phenotype. Moreover, overexpression of p75 NTR in KSC results in a keratinocyte subpopulation with the features of TA cells (73). These results indicate that p75 NTR could act as a “switch on-off” protein that critically regulates KSC-progeny transition and differentiation in human epidermis (Figure 1).…”

“…p75 NTR levels are strikingly reduced in psoriatic TA (57), and the lack of p75 NTR seems to account for the reduced apoptosis of psoriatic keratinocytes. Indeed, BDNF fail to induce cell death in these cells, while overexpression of p75 NTR restores their susceptibility to apoptosis (73). These findings suggest that alterations of the TA cell in psoriasis are at least in part due to a defect in p75 NTR .…”

Fast isolation and expansion of multipotent cells from adipose tissue based on chitosan-selected primary culture

“…The CD271 positive ASCs may retain the sphere-forming ability of NCSCs on chitosan which separate them from the CD271 negative cells on chitosan. On the other hand, literature has indicated that CD271 was upregulated in subconfluent keratinocytes under high calcium conditions [52]. In our previous study, we found that calcium binding capacity of chitosan membranes was found to change the cell-substrate and cellecell interactions to modulate the process of spheroid formation.…”

P75 neurotrophin receptor activates epidermal stem cell differentiation via ERK, JNK and AKT pathways

“…p75NTR, a member of tumor necrosis factor receptor superfamily, comprises three domains, including an extracellular domain, a transmembrane domain, and an intracellular domain. Of three domains, the extracellular domain has four cysteine rich repeats, and is required for interaction of NGF-p75NTR [17][18][19]. Once NGFp75NTR compounds occur, p75NTR can regulate cell apoptosis, proliferation and differentiation.…”