Dermal Papilla Cell Number Research Articles

189 Integrating single-cell and spatial transcriptomics of human hair follicles to define transcriptional signature of follicular dermal papilla

The follicular dermal papilla (DP) is a specialized hair mesenchymal cell that plays pivotal roles in hair follicle (HF) development and morphogenesis. Although transcriptome data exists for HF, characterization of human DPs at the single-cell level has been unsatisfactory due to the limited number of DP cells under single-cell dissociation condition. To generate a high proportion of mesenchymal cells, we manually isolated anagen HFs and DPs from three human scalp specimens and used these isolated populations for single-cell RNA sequencing (scRNA-seq).

Dermal papilla cell culture under hypoxia

Hair loss is most frequently associated with aging or hormonal imbalances, which result in follicular stem cells not being able to regenerate hair follicles (HFs). Many patients take medication or have hair transplantation to resolve hair loss, but there are limitations such as cost, side effects, and so on. Hair transplantation is a common way to treat severe hair loss. However, hair transplantation is based on redistribution of hair follicles without any new follicle formation. Lots of researchers have focused on developing methods to regenerate new hair follicles. Reduced HFs results in progressive hair thinning/loss, and is associated with a failure to maintain the right number of dermal papilla cells (DPC), which specifies hair size, shape and lifecycle. DPCs play a key role in hair regeneration. Therefore, tremendous efforts have been made to promote DPCs’ ability to induce new hair growth. This study looked at how to use hypoxia, a cue that regulates many processes in the body, to improve culture conditions (how the cells are grown in the lab) for DPCs, to help produce DPCs in vitro (in the lab) and maintain their hair inductivity in vivo (in people).

Characterization of Human Dermal Papilla Cells in Alginate Spheres

Maintenance of trichogenecity of dermal papilla cells (DPCs) have been a problem during cell therapy for androgenic alopecia, as they lose their regenerative potential in in vitro culture. Various spheroid culture techniques are used to increase and maintain trichogenecity of these cells. However, there are some critical drawbacks in these methods. Applying a hydrocell plate for sphere formation or hanging drop methods by hand would be difficult to control the size and cell density inside it. It would be difficult to commercialize or mass production for clinical therapy. In aim to address and overcome these drawbacks, we have introduced alginate sphere. The alginate sphere of DPCs were prepared by electrospinning at different voltages to control the size of sphere. Then the obtained alginate spheres were evaluated for cellular dynamics and density of DPCs under different conditions. In this study, we found that DPCs do not proliferate in alginate sphere. However, the number of DPCs were maintained and found to be in dormant state. Further, the dormant DPCs in the alginate sphere have upregulated DPC signature genes (SOX2, ALPL, WIF1, Noggin, BMP4 and VCAN) and proliferative capacity. Thus, we speculate that alginate sphere environment maintains the dormancy of DPCs with increased trichogenecity.

Stabilization of β-Catenin Does Not Increase Dermal Papilla Cell Number in the Hair Follicle

Stabilization of β-Catenin Does Not Increase Dermal Papilla Cell Number in the Hair Follicle

The dermal papilla: an instructive niche for epithelial stem and progenitor cells in development and regeneration of the hair follicle.

The dermal papilla (DP) of the hair follicle is both a chemical and physical niche for epithelial progenitor cells that regenerate the cycling portion of the hair follicle and generate the hair shaft. Here, we review experiments that revealed the importance of the DP in regulating the characteristics of the hair shaft and frequency of hair follicle regeneration. More recent work showed that the size of this niche is dynamic and actively regulated and reduction in DP cell number per follicle is sufficient to cause hair thinning and loss. The formation of the DP during follicle neogenesis provides a context to contemplate the mechanisms that maintain DP size and the potential to exploit these processes for hair preservation or restoration.

Dermal papilla cell number specifies hair size, shape and cycling and its reduction causes follicular decline

Although the hair shaft is derived from the progeny of keratinocyte stem cells in the follicular epithelium, the growth and differentiation of follicular keratinocytes is guided by a specialized mesenchymal population, the dermal papilla (DP), that is embedded in the hair bulb. Here we show that the number of DP cells in the follicle correlates with the size and shape of the hair produced in the mouse pelage. The same stem cell pool gives rise to hairs of different sizes or types in successive hair cycles, and this shift is accompanied by a corresponding change in DP cell number. Using a mouse model that allows selective ablation of DP cells in vivo, we show that DP cell number dictates the size and shape of the hair. Furthermore, we confirm the hypothesis that the DP plays a crucial role in activating stem cells to initiate the formation of a new hair shaft. When DP cell number falls below a critical threshold, hair follicles with a normal keratinocyte compartment fail to generate new hairs. However, neighbouring follicles with a few more DP cells can re-enter the growth phase, and those that do exploit an intrinsic mechanism to restore both DP cell number and normal hair growth. These results demonstrate that the mesenchymal niche directs stem and progenitor cell behaviour to initiate regeneration and specify hair morphology. Degeneration of the DP population in mice leads to the types of hair thinning and loss observed during human aging, and the results reported here suggest novel approaches to reversing hair loss.

Dermal papilla cell number specifies hair size, shape and cycling and its reduction causes follicular decline

Although the hair shaft is derived from the progeny of keratinocyte stem cells in the follicular epithelium, the growth and differentiation of follicular keratinocytes is guided by a specialized mesenchymal population, the dermal papilla (DP), that is embedded in the hair bulb. Here we show that the number of DP cells in the follicle correlates with the size and shape of the hair produced in the mouse pelage. The same stem cell pool gives rise to hairs of different sizes or types in successive hair cycles, and this shift is accompanied by a corresponding change in DP cell number. Using a mouse model that allows selective ablation of DP cells in vivo, we show that DP cell number dictates the size and shape of the hair. Furthermore, we confirm the hypothesis that the DP plays a crucial role in activating stem cells to initiate the formation of a new hair shaft. When DP cell number falls below a critical threshold, hair follicles with a normal keratinocyte compartment fail to generate new hairs. However, neighbouring follicles with a few more DP cells can re-enter the growth phase, and those that do exploit an intrinsic mechanism to restore both DP cell number and normal hair growth. These results demonstrate that the mesenchymal niche directs stem and progenitor cell behaviour to initiate regeneration and specify hair morphology. Degeneration of the DP population in mice leads to the types of hair thinning and loss observed during human aging, and the results reported here suggest novel approaches to reversing hair loss.

Restoration of the intrinsic properties of human dermal papilla in vitro

The dermal papilla (DP) plays pivotal roles in hair follicle morphogenesis and cycling. However, characterization and/or propagation of human DPs have been unsatisfactory because of the lack of efficient isolation methods and the loss of innate characteristics in vitro. We hypothesized that culture conditions sustaining the intrinsic molecular signature of the human DP could facilitate expansion of functional DP cells. To test this, we first characterized the global gene expression profile of microdissected, non-cultured human DPs. We performed a 'two-step' microarray analysis to exclude the influence of unwanted contaminants in isolated DPs and successfully identified 118 human DP signature genes, including 38 genes listed in the mouse DP signature. The bioinformatics analysis of the DP gene list revealed that WNT, BMP and FGF signaling pathways were upregulated in intact DPs and addition of 6-bromoindirubin-3'-oxime, recombinant BMP2 and basic FGF to stimulate these respective signaling pathways resulted in maintained expression of in situ DP signature genes in primarily cultured human DP cells. More importantly, the exposure to these stimulants restored normally reduced DP biomarker expression in conventionally cultured DP cells. Cell growth was moderate in the newly developed culture medium. However, rapid DP cell expansion by conventional culture followed by the restoration by defined activators provided a sufficient number of DP cells that demonstrated characteristic DP activities in functional assays. The study reported here revealed previously unreported molecular mechanisms contributing to human DP properties and describes a useful technique for the investigation of human DP biology and hair follicle bioengineering.

β-catenin Activity in the Dermal Papilla Regulates Morphogenesis and Regeneration of Hair

The activity of keratinocytes in the hair follicle is regulated by signals from a specialized mesenchymal niche, the dermal papilla (DP). Here, mice expressing cre recombinase in the DP were developed to probe the interaction between follicular keratinocytes and the DP in vivo. Inactivation of the beta-catenin gene within DP of fully developed hair follicles results in dramatically reduced proliferation of the progenitors and their progeny that generate the hair shaft, and, subsequently, premature induction of the destructive phase of the hair cycle. It also prevents regeneration of the cycling follicle from stem cells. Gene expression analysis reveals that beta-catenin activity in the DP regulates signaling pathways, including FGF and IGF, that can mediate the DP's inductive effects. This study reveals a signaling loop that employs Wnt/beta-catenin signaling in both epithelial progenitor cells and their mesenchymal niche to govern and coordinate the interactions between these compartments to guide hair morphogenesis.

Factors related to collagen gel contraction in hair follicle organotypic culture

To investigate the effects of rat tail collagen, hair follicle dermal papilla cells and hair follicle epithelium cells on collagen gel contraction in organotypic culture. The hair follicle organotypic culture was prepared with different concentrations of rat tail collagen, different number of dermal papilla cells and hair follicle epithelium cells in DMEM medium, after cultured for 10 days the diameter of collagen gel was measured. The concentration of rat tail collagen, hair follicle dermal papilla cells and hair follicle epithelium cells significantly influenced on collagen gel contraction in organotypic culture (P<0.01). The contraction of collagen gel was negatively related to the concentration of rat tail collagen, while the concentration of dermal papilla cells and hair follicle epithelium cells was positively related to the contraction of collagen gel. The key factor influencing collagen gel contraction in organotypic culture is the concentration of rat tail collagen, hair follicle dermal papilla cells and hair follicle epithelium cells.