title: Bifunctional ectodermal stem cells around the nail display dual fate homeostasis and adaptive wounding response toward nail regeneration.
abstract: Regulation of adult stem cells (SCs) is fundamental for organ maintenance and tissue regeneration. On the body surface, different ectodermal organs exhibit distinctive modes of regeneration and the dynamics of their SC homeostasis remain to be unraveled. A slow cycling characteristic has been used to identify SCs in hair follicles and sweat glands; however, whether a quiescent population exists in continuously growing nails remains unknown. Using an in vivo label retaining cells (LRCs) system, we detected an unreported population of quiescent cells within the basal layer of the nail proximal fold, organized in a ring-like configuration around the nail root. These nail LRCs express the hair stem cell marker, keratin 15 (K15), and lineage tracing show that these K15-derived cells can contribute to both the nail structure and peri-nail epidermis, and more toward the latter. Thus, this stem cell population is bifunctional. Upon nail plucking injury, the homeostasis is tilted with these SCs dominantly delivering progeny to the nail matrix and differentiated nail plate, demonstrating their plasticity to adapt to wounding stimuli. Moreover, in vivo engraftment experiments established that transplanted nail LRCs can actively participate in functional nail regeneration. Transcriptional profiling of isolated nail LRCs revealed bone morphogenetic protein signaling favors nail differentiation over epidermal fate. Taken together, we have found a previously unidentified ring-configured population of bifunctional SCs, located at the interface between the nail appendage organ and adjacent epidermis, which physiologically display coordinated homeostatic dynamics but are capable of rediverting stem cell flow in response to injury.
authors.affiliation: Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, Department of Pathology, and.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Leung
authors.affiliation: Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, Department of Pathology, and.
authors.forename: Eve
authors.initials: E
authors.lastname: Kandyba
authors.affiliation: Norris Medical Library, University of Southern California, Los Angeles, CA 90033; and.
authors.forename: Yi-Bu
authors.initials: YB
authors.lastname: Chen
authors.affiliation: Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research.
authors.forename: Seth
authors.initials: S
authors.lastname: Ruffins
authors.affiliation: Department of Pathology, and International Research Center of Wound Repair and Regeneration, Institute of Clinical Medicine, Cheng Kung University, Tainan City 70101, Taiwan.
authors.forename: Cheng-Ming
authors.initials: CM
authors.lastname: Chuong
authors.affiliation: Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, Department of Pathology, and kkobiela@med.usc.edu.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kobielak
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D004475:Ectoderm / Q000166:cytology*; D000078404:Epidermal Cells; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006706:Homeostasis; D006724:Hoof and Claw / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D012038:Regeneration; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D014158:Transcription, Genetic; D014945:Wound Healing
chemical_list: D019485:Bone Morphogenetic Proteins; D049452:Green Fluorescent Proteins
keywords: BMP signaling; nail proximal fold stem cells; nail stem cells; skin stem cells