Use of human intra-tissue stem/progenitor cells and induced pluripotent stem cells for hair follicle regeneration

Ohyama, Manabu

doi:10.1186/s41232-019-0093-1

Cited by 30 publications

(26 citation statements)

References 98 publications

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“…The hair follicle is a unique mini organ that self-renews throughout its lifetime. Many stem cell populations reside within human hair follicles and enable their regeneration [ 66 ]. Stem cell pluripotency plays a crucial role in cell fate decisions by controlling self-renewal and differentiation [ 44 , 67 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Signatures of Selection for Cashmere Traits in Chinese Goats

Jin

Lü

Fei

et al. 2020

Animals

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Inner Mongolia and Liaoning cashmere goats in China are well-known for their cashmere quality and yield. Thus, they are great models for identifying genomic regions associated with cashmere traits. Herein, 53 Inner Mongolia cashmere goats, Liaoning cashmere goats and Huanghuai goats were genotyped, and 53,347 single-nucleotide polymorphisms (SNPs) were produced using the Illumina Caprine 50K SNP chip. Additionally, we identified some positively selected SNPs by analyzing Fst and XP-EHH. The top 5% of SNPs had selection signatures. After gene annotation, 222 and 173 candidate genes were identified in Inner Mongolia and Liaoning cashmere goats, respectively. Several genes were related to hair follicle development, such as TRPS1, WDR74, LRRC14, SPTLC3, IGF1R, PADI2, FOXP1, WNT10A and CSN3. Gene enrichment analysis of these cashmere trait-associated genes related 67 enriched signaling pathways that mainly participate in hair follicle development and stem cell pluripotency regulation. Furthermore, we identified 20 overlapping genes that were selected in both cashmere goat breeds. Among these overlapping genes, WNT10A and CSN3, which are associated with hair follicle development, are potentially involved in cashmere production. These findings may improve molecular breeding of cashmere goats in the future.

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Section: Discussionmentioning

confidence: 99%

Genetic Signatures of Selection for Cashmere Traits in Chinese Goats

Jin

Lü

Fei

et al. 2020

Animals

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“…For cell fate 3, we enriched the apoptotic signaling pathway, Rab protein signal transduction, PID DELTA NP63 pathway, PID P73 pathway, PID BETA CATENIN NUC pathway, PID P53 DOWNSTREAM pathway, ERAD pathway, and PID MTOR 4 pathway in geneset1, which further revealed the function of the middle cell 1 in hair follicle apoptosis in cell fate 2. In addition, we enriched the TNFR2 non-canonical NF-kB pathway in geneset2, Wnt signaling pathway, signaling by NOTCH, and MAPK6/MAPK4 signaling, to reveal the function of intermediate cells 0 in hair follicle development [45,46]. These two intermediate cells revealed a crosstalk process of apoptosis and development during hair follicle transition [47].…”

Section: Discussionmentioning

confidence: 99%

Single-cell sequencing reveals the intermediate cell state and function of dermal papilla cells in the hair follicle cycle of cashmere goats

Yang¹,

Liu²,

Che³

et al. 2020

Preprint

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Background: Human hair loss and regeneration has stimulated interest in the natural hair cycle worldwide; however, such research is difficult because the periodicity of human or mouse hair is not visually obvious. Dermal papilla cells (DP cells) play an important role in the development of hair follicles, but knowledge of the differentiation and mechanisms of DP stem cells during transition through the hair follicle cycle are still limited, although some studies have reported that DP cells may have an intermediate cell state during differentiation, the classification and function of specific cell states are not clear. Results: Here, we used cashmere goats, that have obvious periodicity of hair follicles, as model animals and, based on unbiased single cell RNA sequencing, we identified and isolated DP cell data. Pseudotime ordering analysis was used to successfully construct a DP cell lineage differentiation trajectory and revealed the sequential activation of key genes, signaling pathways, and functions involved in cell fate decisions. At the same time, we analyzed the mechanisms of different cell fates and revealed the function of four different intermediate cells: Intermediate cells 10 showed important functions in the growth of cashmere and maintenance of cashmere attachment to the skin; intermediate cells 1 revealed important functions in the process of apoptosis and cashmere shedding of secondary hair follicles; intermediate cells 0 initiated new follicular cycles and completed the migration of hair follicles and the occurrence of cashmere; and intermediate cells 15 are suggested to be DP progenitor cells. Conclusions: In development and apoptosis, inner bulge cells not only earlier than outer bulge cells, but occurred faster and was more thorough,this helps a deeper understanding of the role of bulge cells. Pseudogenes play another important role in function which promoted the competitive endogenous RNA (ceRNA) hybridization of pseudogenes.In different hair follicle cycles, DP cells will differentiate into different intermediate state cells and perform different functions, and the marker genes of the cells also changed. Intermediate cells 10 showed important functions in the growth of cashmere and maintenance of cashmere attachment to the skin; intermediate cells 1 revealed important functions in the process of apoptosis and cashmere shedding of secondary hair follicles; intermediate cells 0 initiated new follicular cycles and completed the migration of hair follicles and the occurrence of cashmere; and intermediate cells 15 are DP progenitor cells, this conclusion provides an unprecedented deeper understanding of the function of DP cells.

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“…Following the previously described protocol for the chamber assay [ 4 ], epidermal and dermal cells were isolated from BALB/cCrSlc mouse embryos (E18–19) and transplanted into the chambers grafted onto the fascia of SCID mice. FGF7 (5 μg/mL), FGF9 (5 μg/mL), or PBS as control was injected at the dose of 100 μL through minute pole on the top of silicon chambers [ 14 ] every other day for 2 weeks, before the silicon chambers were removed. Four weeks after the removal, the regenerated back skin was harvested for the histopathological analysis.…”

Section: Methodsmentioning

confidence: 99%

Altered FGF expression profile in human scalp-derived fibroblasts upon WNT activation: implication of their role to provide folliculogenetic microenvironment

et al. 2020

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Background Hair follicle (HF) formation and growth are sustained by epithelial-mesenchymal interaction via growth factors and cytokines. Pivotal roles of FGFs on HF regeneration and neogenesis have been reported mainly in rodent models. FGF expression is regulated by upstream pathways, represented by canonical WNT signaling; however, how FGFs influence on human folliculogenesis remains elusive. The aim of this study is to assess if human scalp-derived fibroblasts (sFBs) are able to modulate their FGF expression profile in response to WNT activation and to evaluate the influence of WNT-activated or suppressed FGFs on folliculogenesis. Methods Dermal papilla cells (DPCs), dermal sheath cells (DSCs), and sFBs were isolated from the human scalp and cultured independently. The gene expression profile of FGFs in DPCs, DSCs, and sFBs and the influence of WNT activator, CHIR99021, on FGF expression pattern in sFBs were evaluated by reverse transcription polymerase chain reaction, which were confirmed at protein level by western blotting analysis. The changes in the expression of DPC or keratinocyte (KC) biomarkers under the presence of FGF7 or 9 were examined in both single and co-culture assay of DPCs and/or KCs. The influence of FGF 7 and FGF 9 on hair morphogenesis and growth was analyzed in vivo using mouse chamber assay. Results In single culture, sFBs were distinguished from DPCs and DSCs by relatively high expression of FGF5 and FGF18, potential inducers of hair cycle retardation or catagen phase. In WNT-activated state, sFBs downregulated FGF7 while upregulating FGF9, a positive regulator of HF morphogenesis, FGF16 and FGF20 belonging to the same FGF subfamily. In addition, CHIR99021, a WNT activator, dose-dependently modulated FGF7 and 9 expression to be folliculogenic. Altered expressions of FGF7 and FGF9 by CHIR99021 were confirmed at protein level. Supplementation of FGF9 to cultured DPCs resulted in upregulation of representative DP biomarkers and this tendency was sustained, when DPCs were co-cultured with KCs. In mouse chamber assay, FGF9 increased both the number and the diameter of newly formed HFs, while FGF7 decreased HF diameter. Conclusion The results implied that sFBs support HF formation by modulating regional FGF expression profile responding to WNT activation.

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Use of human intra-tissue stem/progenitor cells and induced pluripotent stem cells for hair follicle regeneration

Cited by 30 publications

References 98 publications

Genetic Signatures of Selection for Cashmere Traits in Chinese Goats

Genetic Signatures of Selection for Cashmere Traits in Chinese Goats

Single-cell sequencing reveals the intermediate cell state and function of dermal papilla cells in the hair follicle cycle of cashmere goats

Altered FGF expression profile in human scalp-derived fibroblasts upon WNT activation: implication of their role to provide folliculogenetic microenvironment

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