scholarly journals Tp63-expressing adult epithelial stem cells cross lineages boundaries revealing latent hairy skin competence

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Stéphanie Claudinot ◽  
Jun-Ichi Sakabe ◽  
Hideo Oshima ◽  
Christèle Gonneau ◽  
Thimios Mitsiadis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Hair Follicle ◽  
Hair Follicles ◽  
Epidermal Cells ◽  
Epithelial Stem Cells ◽  
Sebaceous Glands ◽  
Embryonic Origin ◽  
Lineage Markers

Abstract The formation of hair follicles, a landmark of mammals, requires complex mesenchymal–epithelial interactions and it is commonly believed that embryonic epidermal cells are the only cells that can respond to hair follicle morphogenetic signals in vivo. Here, we demonstrate that epithelial stem cells of non-skin origin (e.g. that of cornea, oesophagus, vagina, bladder, prostate) that express the transcription factor Tp63, a master gene for the development of epidermis and its appendages, can respond to skin morphogenetic signals. When exposed to a newborn skin microenvironment, these cells express hair-follicle lineage markers and contribute to hair follicles, sebaceous glands and/or epidermis renewal. Our results demonstrate that lineage restriction is not immutable and support the notion that all Tp63-expressing epithelial stem cells, independently of their embryonic origin, have latent skin competence explaining why aberrant hair follicles or sebaceous glands are sometimes observed in non-skin tissues (e.g. in cornea, vagina or thymus).

scholarly journals Expansion of Hair Follicle Stem Cells Sticking to Isolated Sebaceous Glands to Generate in Vivo Epidermal Structures

2016 ◽  
Vol 25 (11) ◽  
pp. 2071-2082 ◽  
Author(s):  
Huishan Zhang ◽  
Huashan Zhao ◽  
Jingqiao Qiao ◽  
Shoubing Zhang ◽  
Shuang Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hair Follicle ◽  
Sebaceous Glands ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

scholarly journals Establishment of an Efficient Primary Culture System for Human Hair Follicle Stem Cells Using the Rho-Associated Protein Kinase Inhibitor Y-27632

2021 ◽  
Vol 9 ◽  
Author(s):  
Lihong Wen ◽  
Yong Miao ◽  
Zhexiang Fan ◽  
Jiarui Zhang ◽  
Yixuan Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hair Follicle ◽  
Culture System ◽  
Hair Follicles ◽  
Human Hair Follicle ◽  
Rock Inhibitor ◽  
Hair Follicle Stem Cells ◽  
Human Fibronectin ◽  
Follicle Stem Cells

BackgroundHair follicle tissue engineering is a promising strategy for treating hair loss. Human hair follicle stem cells (hHFSCs), which play a key role in the hair cycle, have potential applications in regenerative medicine. However, previous studies did not achieve efficient hHFSC expansion in vitro using feeder cells. Therefore, there is a need to develop an efficient primary culture system for the expansion and maintenance of hHFSCs.MethodsThe hHFSCs were obtained by two-step proteolytic digestion combined with microscopy. The cell culture dishes were coated with human fibronectin and inoculated with hHFSCs. The hHFSCs were harvested using a differential enrichment procedure. The effect of Rho-associated protein kinase (ROCK) inhibitor Y-27632, supplemented in keratinocyte serum-free medium (K-SFM), on adhesion, proliferation, and stemness of hHFSCs and the underlying molecular mechanisms were evaluated.ResultsThe hHFSCs cultured in K-SFM, supplemented with Y-27632, exhibited enhanced adhesion and proliferation. Additionally, Y-27632 treatment maintained the stemness of hHFSCs and promoted the ability of hHFSCs to regenerate hair follicles in vivo. However, Y-27632-induced proliferation and stemness in hHFSCs were conditional and reversible. Furthermore, Y-27632 maintained propagation and stemness of hHFSCs through the ERK/MAPK pathway.ConclusionAn efficient short-term culture system for primary hHFSCs was successfully established using human fibronectin and the ROCK inhibitor Y-27632, which promoted the proliferation, maintained the stemness of hHFSCs and promoted the ability to regenerate hair follicles in vivo. The xenofree culturing method used in this study provided a large number of high-quality seed cells, which have applications in hair follicle tissue engineering and stem cell therapy.

scholarly journals Pre-aggregation of scalp progenitor dermal and epidermal stem cells activates the WNT pathway and promotes hair follicle formation in in vitro and in vivo systems

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yiqun Su ◽  
Jie Wen ◽  
Junrong Zhu ◽  
Zhiwei Xie ◽  
Chang Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hair Follicle ◽  
Progenitor Cells ◽  
Wnt Pathway ◽  
Three Dimensional ◽  
Epidermal Cells ◽  
Type I ◽  
Epidermal Stem Cells

Abstract Background Billions of dollars are invested annually by pharmaceutical companies in search of new options for treating hair loss conditions; nevertheless, the challenge remains. One major limitation to hair follicle research is the lack of effective and efficient drug screening systems using human cells. Organoids, three-dimensional in vitro structures derived from stem cells, provide new opportunities for studying organ development, tissue regeneration, and disease pathogenesis. The present study focuses on the formation of human hair follicle organoids. Methods Scalp-derived dermal progenitor cells mixed with foreskin-derived epidermal stem cells at a 2:1 ratio aggregated in suspension to form hair follicle-like organoids, which were confirmed by immunostaining of hair follicle markers and by molecular dye labeling assays to analyze dermal and epidermal cell organization in those organoids. The hair-forming potential of organoids was examined using an in vivo transplantation assay. Results Pre-aggregation of dermal and epidermal cells enhanced hair follicle formation in vivo. In vitro pre-aggregation initiated the interactions of epidermal and dermal progenitor cells resulting in activation of the WNT pathway and the formation of pear-shape structures, named type I aggregates. Cell-tracing analysis showed that the dermal and epidermal cells self-assembled into distinct epidermal and dermal compartments. Histologically, the type I aggregates expressed early hair follicle markers, suggesting the hair peg-like phase of hair follicle morphogenesis. The addition of recombinant WNT3a protein to the medium enhanced the formation of these aggregates, and the Wnt effect could be blocked by the WNT inhibitor, IWP2. Conclusions In summary, our system supports the rapid formation of a large number of hair follicle organoids (type I aggregates). This system provides a platform for studying epithelial-mesenchymal interactions, for assessing inductive hair stem cells and for screening compounds that support hair follicle regeneration.

scholarly journals Polycomb repressive complex 2 in adult hair follicle stem cells is dispensable for hair regeneration

PLoS Genetics ◽  
2021 ◽  
Vol 17 (12) ◽  
pp. e1009948
Author(s):  
Pooja Flora ◽  
Meng-Yen Li ◽  
Phillip M. Galbo ◽  
Maider Astorkia ◽  
Deyou Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hair Follicle ◽  
Hair Follicles ◽  
Polycomb Repressive Complex ◽  
Polycomb Repressive Complex 2 ◽  
Activated State ◽  
Hair Regeneration ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

Hair follicle stem cells (HFSCs) are multipotent cells that cycle through quiescence and activation to continuously fuel the production of hair follicles. Prior genome mapping studies had shown that tri-methylation of histone H3 at lysine 27 (H3K27me3), the chromatin mark mediated by Polycomb Repressive Complex 2 (PRC2), is dynamic between quiescent and activated HFSCs, suggesting that transcriptional changes associated with H3K27me3 might be critical for proper HFSC function. However, functional in vivo studies elucidating the role of PRC2 in adult HFSCs are lacking. In this study, by using in vivo loss-of-function studies we show that, surprisingly, PRC2 plays a non-instructive role in adult HFSCs and loss of PRC2 in HFSCs does not lead to loss of HFSC quiescence or changes in cell identity. Interestingly, RNA-seq and immunofluorescence analyses of PRC2-null quiescent HFSCs revealed upregulation of genes associated with activated state of HFSCs. Altogether, our findings show that transcriptional program under PRC2 regulation is dispensable for maintaining HFSC quiescence and hair regeneration.

Hair Follicle Stem Cells Derived from Single Rat Vibrissa via Organ Culture Reconstitute Hair Follicles in Vivo

2012 ◽  
Vol 21 (6) ◽  
pp. 1075-1085 ◽  
Author(s):  
Shoubing Zhang ◽  
Huimin Hu ◽  
Huishan Zhang ◽  
Shuang Liu ◽  
Shu Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Organ Culture ◽  
Hair Follicle ◽  
Hair Follicles ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

scholarly journals Rac1 Is Crucial for Hair Follicle Integrity but Is Not Essential for Maintenance of the Epidermis

2006 ◽  
Vol 26 (18) ◽  
pp. 6957-6970 ◽  
Author(s):  
Anna Chrostek ◽  
Xunwei Wu ◽  
Fabio Quondamatteo ◽  
Rong Hu ◽  
Anna Sanecka ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Hair Follicles ◽  
Small Gtpase ◽  
Epidermal Keratinocytes ◽  
Sebaceous Glands ◽  
Cellular Processes ◽  
Normal Differentiation ◽  
Deficient Mice

ABSTRACT Rac1 is a small GTPase that regulates the actin cytoskeleton but also other cellular processes. To investigate the function of Rac1 in skin, we generated mice with a keratinocyte-restricted deletion of the rac1 gene. Rac1-deficient mice lost nearly all of their hair within a few weeks after birth. The nonpermanent part of mutant hair follicles developed constrictions; lost expression of hair follicle-specific keratins, E-cadherin, and α6 integrin; and was eventually removed by macrophages. The permanent part of hair follicles and the sebaceous glands were maintained, but no regrowth of full-length hair follicles was observed. In the skin of mutant mice, epidermal keratinocytes showed normal differentiation, proliferation, cell-cell contacts, and basement membrane deposition, demonstrating no obvious defects of Rac1-deficient epidermis in vivo. In vitro, Rac1-null keratinocytes displayed a strong spreading defect and slightly impaired adhesion. These data show that Rac1 plays an important role in sustaining the integrity of the lower part of hair follicles but not in maintenance of the epidermis.

scholarly journals Interfollicular epidermal stem-like cells for the recreation of the hair follicle epithelial compartment

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carla M. Abreu ◽  
Rogério P. Pirraco ◽  
Rui L. Reis ◽  
Mariana T. Cerqueira ◽  
Alexandra P. Marques
Keyword(s):  
Hair Follicle ◽  
Cell Sorting ◽  
Dermal Papilla ◽  
Epidermal Keratinocytes ◽  
Sebaceous Glands ◽  
Phenotypic Profile ◽  
Cell Source ◽  
Epithelial Compartment ◽  
The Ideal

Abstract Background Hair follicle (HF) development and growth are dependent on epithelial-mesenchymal interactions (EMIs). Dermal papilla (DP) cells are recognized as the key inductive mesenchymal player, but the ideal source of receptive keratinocytes for human HF regeneration is yet to be defined. We herein investigated whether human interfollicular epidermal keratinocytes with stem-like features (EpSlKCs), characterized by a α6bri/CD71dim expression, can replace human hair follicular keratinocytes (HHFKCs) for the recreation of the HF epithelium and respective EMIs. Methods The α6bri/CD71dim cellular fraction was selected from the whole interfollicular keratinocyte population through fluorescence-activated cell sorting and directly compared with follicular keratinocytes in terms of their proliferative capacity and phenotype. The crosstalk with DP cells was studied in an indirect co-culture system, and EpSlKC hair forming capacity tested in a hair reconstitution assay when combined with DP cells. Results EpSlKCs exhibited a phenotypic profile similar to follicular keratinocytes and were capable of increasing DP cell proliferation and, for short co-culture times, the number of alkaline phosphatase-active cells, suggesting an improvement of their inductivity. Moreover, the recreation of immature HFs and sebaceous glands was observed after EpSlKC and DP cell co-grafting in nude mice. Conclusions Our results suggest that EpSlKCs are akin to follicular keratinocytes and can crosstalk with DP cells, contributing to HF morphogenesis in vivo, thus representing an attractive epithelial cell source for hair regeneration strategies.

scholarly journals A Mouse Model for Studying Stem Cell Effects on Regeneration of Hair Follicle Outer Root Sheaths

2020 ◽  
Vol 15 (1) ◽  
pp. 41-50
Author(s):  
Jingxu Guo ◽  
Shuwei Li ◽  
Hongyang Wang ◽  
Tinghui Wu ◽  
Zhenhui Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mouse Model ◽  
Hair Follicle ◽  
Smooth Muscle Actin ◽  
Hair Follicles ◽  
Alpha Smooth Muscle Actin ◽  
Papillary Structure ◽  
Glass Membrane

AbstractObjectiveStem cells hold promise for treating hair loss. Here an in vitro mouse model was developed using outer root sheaths (ORSs) isolated from hair follicles for studying stem cell-mediated dermal papillary regeneration.MethodsUnder sterile conditions, structurally intact ORSs were isolated from hair follicles of 3-day-old Kunming mice and incubated in growth medium. Samples were collected daily for 5 days. Stem cell distribution, proliferation, differentiation, and migration were monitored during regeneration.ResultsCell proliferation began at the glass membrane periphery then spread gradually toward the membrane center, with the presence of CD34 and CD200 positive stem cells involved in repair initiation. Next, CD34 positive stem cells migrated down the glass membrane, where some participated in ORS formation, while other CD34 cells and CD200 positive cells migrated to hair follicle centers. Within the hair follicle matrix, stem cells divided, grew, differentiated and caused outward expansion of the glass membrane to form a dermal papillary structure containing alpha-smooth muscle actin. Neutrophils attracted to the wound site phagocytosed bacterial and cell debris to protect regenerating tissue from infection.ConclusionIsolated hair follicle ORSs can regenerate new dermal papillary structures in vitro. Stem cells and neutrophils play important roles in the regeneration process.

scholarly journals Therapeutic Potential of Stem Cells in Follicle Regeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Agnieszka Owczarczyk-Saczonek ◽  
Magdalena Krajewska-Włodarczyk ◽  
Anna Kruszewska ◽  
Łukasz Banasiak ◽  
Waldemar Placek ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Therapeutic Potential ◽  
Cell Activity ◽  
Hair Follicles ◽  
Treatment Technique ◽  
Androgenic Alopecia ◽  
The Metabolic Syndrome ◽  
Increased Risk

Alopecia is caused by a variety of factors which affect the hair cycle and decrease stem cell activity and hair follicle regeneration capability. This process causes lower self-acceptance, which may result in depression and anxiety. However, an early onset of androgenic alopecia is associated with an increased incidence of the metabolic syndrome and an increased risk of the cardiac ischaemic disease. The ubiquity of alopecia provides an encouragement to seek new, more effective therapies aimed at hair follicle regeneration and neoregeneration. We know that stem cells can be used to regenerate hair in several therapeutic strategies: reversing the pathological mechanisms which contribute to hair loss, regeneration of complete hair follicles from their parts, and neogenesis of hair follicles from a stem cell culture with isolated cells or tissue engineering. Hair transplant has become a conventional treatment technique in androgenic alopecia (micrografts). Although an autologous transplant is regarded as the gold standard, its usability is limited, because of both a limited amount of material and a reduced viability of cells obtained in this way. The new therapeutic options are adipose-derived stem cells and stem cells from Wharton’s jelly. They seem an ideal cell population for use in regenerative medicine because of the absence of immunogenic properties and their ease of obtainment, multipotential character, ease of differentiating into various cell lines, and considerable potential for angiogenesis. In this article, we presented advantages and limitations of using these types of cells in alopecia treatment.

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