scholarly journals Mitochondrial aerobic respiration is activated during hair follicle stem cell differentiation, and its dysfunction retards hair regeneration

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1821 ◽  
Author(s):  
Yan Tang ◽  
Binping Luo ◽  
Zhili Deng ◽  
Ben Wang ◽  
Fangfen Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Differentiation ◽  
Hair Follicle ◽  
Pyruvate Dehydrogenase ◽  
Mitochondrial Respiration ◽  
Redox Balance ◽  
Aerobic Respiration ◽  
Mitochondrial Morphology ◽  
Differentiated Cells ◽  
Hair Regeneration

Background.Emerging research revealed the essential role of mitochondria in regulating stem/progenitor cell differentiation of neural progenitor cells, mesenchymal stem cells and other stem cells through reactive oxygen species (ROS), Notch or other signaling pathway. Inhibition of mitochondrial protein synthesis results in hair loss upon injury. However, alteration of mitochondrial morphology and metabolic function during hair follicle stem cells (HFSCs) differentiation and how they affect hair regeneration has not been elaborated upon.Methods.We compared the difference in mitochondrial morphology and activity between telogen bulge cells and anagen matrix cells. Expression levels of mitochondrial ROS and superoxide dismutase 2 (SOD2) were measured to evaluate redox balance. In addition, the level of pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase (PDH) were estimated to present the change in energetic metabolism during differentiation. To explore the effect of the mitochondrial metabolism on regulating hair regeneration, hair growth was observed after application of a mitochondrial respiratory inhibitor upon hair plucking.Results.During HFSCs differentiation, mitochondria became elongated with more abundant organized cristae and showed higher activity in differentiated cells. SOD2 was enhanced for redox balance with relatively stable ROS levels in differentiated cells. PDK increased in HFSCs while differentiated cells showed enhanced PDH, indicating that respiration switched from glycolysis to oxidative phosphorylation during differentiation. Inhibiting mitochondrial respiration in differentiated hair follicle cells upon hair plucking repressed hair regenerationin vivo.Conclusions.Upon HFSCs differentiation, mitochondria are elongated with more abundant cristae and show higher activity, accompanying with activated aerobic respiration in differentiated cells for higher energy supply. Also, dysfunction of mitochondrial respiration delays hair regeneration upon injury.

scholarly journals Mitochondrial aerobic respiration is activated during hair follicle stem cells differentiation and its dysfunction retards hair regeneration

2016 ◽  
Author(s):  
Yan Tang ◽  
Binping Luo ◽  
Zhili Deng ◽  
Ben Wang ◽  
Fangfen L Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hair Follicle ◽  
Pyruvate Dehydrogenase ◽  
Redox Balance ◽  
Aerobic Respiration ◽  
Mitochondrial Morphology ◽  
Differentiated Cells ◽  
Hair Regeneration ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

Background. Emerging researches revealed the essential role of mitochondria in regulating stem/progenitor cell differentiation of neural progenitor cells, mesenchymal stem cells and other stem cells through reactive oxygen species (ROS), Notch or other signaling pathway. And inhibition of mitochondrial synthesis protein resulted in extension of hair loss upon injury. However, alteration of mitochondrial morphology and metabolic function during hair follicle stem cells (HFSCs) differentiation and how it affects hair regeneration has not been elaborated. Methods. We compared the difference between telogen bulge cells and anagen matrix cells in mitochondrial morphology and activity. Expression levels of mitochondrial ROS and superoxide dismutase 2 (SOD2) were measured for evaluating redox balance. Besides, pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase (PDH) were detected to present the change in energetic metabolism during differentiation. To explore the effect of the mitochondrial metabolism on regulating hair regeneration, hair growth was observed after application of a mitochondrial respiratory inhibitor upon hair plucking. Results. During HFSCs differentiation, mitochondria became elongated with more abundant organized cristae and showed higher activity in differentiated cells. SOD2 was enhanced for redox balance with relatively poised ROS expression levels in differentiated cells. PDK increased in HFSCs while differentiated cells showed enhanced PDH, indicating that respiration converted from glycolysis to oxidative phosphorylation during differentiation. Inhibiting mitochondrial respiration in differentiated hair follicle cells upon hair plucking held back hair regeneration in vivo. Conclusions. Upon HFSCs differentiation, mitochondria was elongated with more abundant cristae and showed higher activity, accompanied with activated aerobic respiration in differentiated cells for higher energy supply. And dysfunction of mitochondrial respiration delays hair regeneration upon injury.

scholarly journals Mitochondrial aerobic respiration is activated during hair follicle stem cells differentiation and its dysfunction retards hair regeneration

2016 ◽  
Author(s):  
Yan Tang ◽  
Binping Luo ◽  
Zhili Deng ◽  
Ben Wang ◽  
Fangfen L Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hair Follicle ◽  
Pyruvate Dehydrogenase ◽  
Redox Balance ◽  
Aerobic Respiration ◽  
Mitochondrial Morphology ◽  
Differentiated Cells ◽  
Hair Regeneration ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

Background. Emerging researches revealed the essential role of mitochondria in regulating stem/progenitor cell differentiation of neural progenitor cells, mesenchymal stem cells and other stem cells through reactive oxygen species (ROS), Notch or other signaling pathway. And inhibition of mitochondrial synthesis protein resulted in extension of hair loss upon injury. However, alteration of mitochondrial morphology and metabolic function during hair follicle stem cells (HFSCs) differentiation and how it affects hair regeneration has not been elaborated. Methods. We compared the difference between telogen bulge cells and anagen matrix cells in mitochondrial morphology and activity. Expression levels of mitochondrial ROS and superoxide dismutase 2 (SOD2) were measured for evaluating redox balance. Besides, pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase (PDH) were detected to present the change in energetic metabolism during differentiation. To explore the effect of the mitochondrial metabolism on regulating hair regeneration, hair growth was observed after application of a mitochondrial respiratory inhibitor upon hair plucking. Results. During HFSCs differentiation, mitochondria became elongated with more abundant organized cristae and showed higher activity in differentiated cells. SOD2 was enhanced for redox balance with relatively poised ROS expression levels in differentiated cells. PDK increased in HFSCs while differentiated cells showed enhanced PDH, indicating that respiration converted from glycolysis to oxidative phosphorylation during differentiation. Inhibiting mitochondrial respiration in differentiated hair follicle cells upon hair plucking held back hair regeneration in vivo. Conclusions. Upon HFSCs differentiation, mitochondria was elongated with more abundant cristae and showed higher activity, accompanied with activated aerobic respiration in differentiated cells for higher energy supply. And dysfunction of mitochondrial respiration delays hair regeneration upon injury.

Lineage potential, plasticity and environmental reprogramming of epithelial stem/progenitor cells

2014 ◽  
Vol 42 (3) ◽  
pp. 637-644 ◽  
Author(s):  
Alessandro W. Amici ◽  
Fatai O. Onikoyi ◽  
Paola Bonfanti
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Cell Therapy ◽  
Hair Follicle ◽  
Progenitor Cells ◽  
Environmental Cues ◽  
Full Potential ◽  
Thymic Epithelium ◽  
Differentiated Cells ◽  
Stratified Epithelia

Recent evidence supports and reinforces the concept that environmental cues may reprogramme somatic cells and change their natural fate. In the present review, we concentrate on environmental reprogramming and fate potency of different epithelial cells. These include stratified epithelia, such as the epidermis, hair follicle, cornea and oesophagus, as well as the thymic epithelium, which stands alone among simple and stratified epithelia, and has been shown recently to contain stem cells. In addition, we briefly discuss the pancreas as an example of plasticity of intrinsic progenitors and even differentiated cells. Of relevance, examples of plasticity and fate change characterize pathologies such as oesophageal metaplasia, whose possible cell origin is still debated, but has important implications as a pre-neoplastic event. Although much work remains to be done in order to unravel the full potential and plasticity of epithelial cells, exploitation of this phenomenon has already entered the clinical arena, and might provide new avenues for future cell therapy of these tissues.

A 3D Cellular Automaton for Cell Differentiation in a Solid Tumor with Plasticity

2018 ◽  
Vol 13 (01) ◽  
pp. 19-28 ◽  
Author(s):  
David H. Margarit ◽  
Lilia Romanelli ◽  
Alejandro J. Fendrik
Keyword(s):  
Stem Cells ◽  
Cell Differentiation ◽  
Cancer Stem Cells ◽  
Cellular Automaton ◽  
Solid Tumor ◽  
Spherical Symmetry ◽  
Differentiated Cells ◽  
Previous State

A model with spherical symmetry is proposed. We analyze the appropriate parameters of cell differentiation for different kinds of cells (Cancer Stem Cells (CSC) and Differentiated Cells (DC)). The plasticity (capacity to return from a DC to its previous state of CSC) is taken into account. Following this hypothesis, the dissemination of CSCs to another organ is analyzed. The location of the cells in the tumor and the plasticity range for possible metastasis is discussed.

Hair Follicle Stem Cells and Hair Regeneration

2020 ◽  
pp. 1-32
Author(s):  
Sung-Jan Lin ◽  
Wen-Yen Huang ◽  
Chih-Chiang Chen ◽  
Mingxing Lei ◽  
Jin-Bon Hong
Keyword(s):  
Stem Cells ◽  
Hair Follicle ◽  
Hair Regeneration ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

scholarly journals Axin2 marks quiescent hair follicle bulge stem cells that are maintained by autocrine Wnt/β-catenin signaling

2016 ◽  
Vol 113 (11) ◽  
pp. E1498-E1505 ◽  
Author(s):  
Xinhong Lim ◽  
Si Hui Tan ◽  
Ka Lou Yu ◽  
Sophia Beng Hui Lim ◽  
Roeland Nusse
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Hair Follicle ◽  
Extended Period ◽  
Lineage Tracing ◽  
Hair Cycle ◽  
Cell Potential ◽  
Differentiated Cells ◽  
Hair Follicle Stem Cells

How stem cells maintain their identity and potency as tissues change during growth is not well understood. In mammalian hair, it is unclear how hair follicle stem cells can enter an extended period of quiescence during the resting phase but retain stem cell potential and be subsequently activated for growth. Here, we use lineage tracing and gene expression mapping to show that the Wnt target gene Axin2 is constantly expressed throughout the hair cycle quiescent phase in outer bulge stem cells that produce their own Wnt signals. Ablating Wnt signaling in the bulge cells causes them to lose their stem cell potency to contribute to hair growth and undergo premature differentiation instead. Bulge cells express secreted Wnt inhibitors, including Dickkopf (Dkk) and secreted frizzled-related protein 1 (Sfrp1). However, the Dickkopf 3 (Dkk3) protein becomes localized to the Wnt-inactive inner bulge that contains differentiated cells. We find that Axin2 expression remains confined to the outer bulge, whereas Dkk3 continues to be localized to the inner bulge during the hair cycle growth phase. Our data suggest that autocrine Wnt signaling in the outer bulge maintains stem cell potency throughout hair cycle quiescence and growth, whereas paracrine Wnt inhibition of inner bulge cells reinforces differentiation.

scholarly journals In VitroNeural Differentiation of Bone Marrow Mesenchymal Stem Cells Carrying the FTH1 Reporter Gene and Detection with MRI

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Tong Mu ◽  
Yong Qin ◽  
Bo Liu ◽  
Xiaoya He ◽  
Yifan Liao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Differentiation ◽  
Reporter Gene ◽  
Neural Differentiation ◽  
Neuron Specific Enolase ◽  
Stem Cell Differentiation ◽  
Blue Staining ◽  
Differentiated Cells

Magnetic resonance imaging (MRI) based on the ferritin heavy chain 1 (FTH1) reporter gene has been used to trace stem cells. However, whether FTH1 expression is affected by stem cell differentiation or whether cell differentiation is affected by reporter gene expression remains unclear. Here, we explore the relationship between FTH1 expression and neural differentiation in the differentiation of mesenchymal stem cells (MSCs) carrying FTH1 into neuron-like cells and investigate the feasibility of using FTH1 as an MRI reporter gene to detect neurally differentiated cells. By inducing cell differentiation with all-trans retinoic acid and a modified neuronal medium, MSCs and MSCs-FTH1 were successfully differentiated into neuron-like cells (Neurons and Neurons-FTH1), and the neural differentiation rates were (91.56±7.89)% and (92.23±7.64)%, respectively. Neuron-specific markers, including nestin, neuron-specific enolase, and microtubule-associated protein-2, were significantly expressed in Neurons-FTH1 and Neurons without noticeable differences. On the other hand, FTH1 was significantly expressed in MSCs-FTH1 and Neurons-FTH1 cells, and the expression levels were not significantly different. The R2 value was significantly increased in MSCs-FTH1 and Neurons-FTH1 cells, which was consistent with the findings of Prussian blue staining, transmission electron microscopy, and intracellular iron measurements. These results suggest that FTH1 gene expression did not affect MSC differentiation into neurons and was not affected by neural differentiation. Thus, MRI reporter gene imaging based on FTH1 can be used for the detection of neurally differentiated cells from MSCs.

Hair Follicle Stem Cells and Hair Regeneration

2020 ◽  
pp. 265-296
Author(s):  
Sung-Jan Lin ◽  
Wen-Yen Huang ◽  
Chih-Chiang Chen ◽  
Mingxing Lei ◽  
Jin-Bon Hong
Keyword(s):  
Stem Cells ◽  
Hair Follicle ◽  
Hair Regeneration ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

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.

scholarly journals A Wnt5a-Cdc42 axis controls aging and rejuvenation of hair-follicle stem cells

2020 ◽  
Author(s):  
Rajiv L Tiwari ◽  
Pratibha Mishra ◽  
Nicola Martin ◽  
Nikhil Oommen George ◽  
Vadim Sakk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wnt Signaling ◽  
Hair Follicle ◽  
Canonical Wnt Signaling ◽  
Hair Regeneration ◽  
Hair Follicle Stem Cells ◽  
Elevated Activity ◽  
Canonical Wnt ◽  
Follicle Stem Cells

SummaryNormal hair growth occurs in cycles, comprising growth (anagen), cessation (catagen) and rest (telogen). Upon aging, the initiation of anagen is significantly delayed, which results in impaired hair regeneration. Hair regeneration is driven by hair follicle stem cells (HFSCs). We show here that aged HFSCs present with a decrease in canonical Wnt signaling and a shift towards non-canonical Wnt5a driven signaling which antagonizes canonical Wnt signaling. Elevated expression of Wnt5a in HFSCs upon aging results in elevated activity of the small RhoGTPase Cdc42 as well as a change in the spatial distribution of Cdc42 within HFSCs. Treatment of aged HFSC with a specific pharmacological inhibitor of Cdc42 activity termed CASIN to suppress the aging-associated elevated activity of Cdc42 restored canonical Wnt signaling in aged HFSCs. Treatment of aged mice in vivo with CASIN induced anagen onset and increased the percentage of anagen skin areas. Aging-associated functional deficits of HFSCs are at least in part intrinsic to HFSCs and can be restored by rational pharmacological approaches.

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