The dermal papilla (DP) provide instructive signals required to activate epithelial progenitors and initiate hair follicle regeneration. DP cell numbers fluctuate over the hair cycle, and hair loss ...is associated with gradual depletion/atrophy of DP cells. How DP cell numbers are maintained in healthy follicles remains unclear. We performed in vivo fate mapping of adult hair follicle dermal sheath (DS) cells to determine their lineage relationship with DP and found that a subset of DS cells are retained following each hair cycle, exhibit self-renewal, and repopulate the DS and the DP with new cells. Ablating these hair follicle dermal stem cells and their progeny retarded hair regrowth and altered hair type specification, suggesting that they function to modulate normal DP function. This work identifies a bipotent stem cell within the adult hair follicle mesenchyme and has important implications toward restoration of hair growth after injury, disease, and aging.
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•Self-renewing hair follicle dermal stem cells (hfDSCs) reside in the dermal sheath•hfDSCs regenerate the dermal sheath and populate the dermal papilla with new cells•The hair follicle niche contains active and quiescent hfDSCs•hfDSCs and their progeny modulate hair growth and specify hair type
Using in vivo fate mapping, Rahmani et al. demonstrate the existence of a bipotent dermal stem cell (hfDSC) that resides in adult hair follicles. At the beginning of each regenerative cycle, hfDSCs repopulate the inductive dermal papilla and dermal sheath and ultimately function to modulate hair growth rate and specify hair type.
Ependymal cells are multi-ciliated cells that form the brain’s ventricular epithelium and a niche for neural stem cells (NSCs) in the ventricular-subventricular zone (V-SVZ). In addition, ependymal ...cells are suggested to be latent NSCs with a capacity to acquire neurogenic function. This remains highly controversial due to a lack of prospective in vivo labeling techniques that can effectively distinguish ependymal cells from neighboring V-SVZ NSCs. We describe a transgenic system that allows for targeted labeling of ependymal cells within the V-SVZ. Single-cell RNA-seq revealed that ependymal cells are enriched for cilia-related genes and share several stem-cell-associated genes with neural stem or progenitors. Under in vivo and in vitro neural-stem- or progenitor-stimulating environments, ependymal cells failed to demonstrate any suggestion of latent neural-stem-cell function. These findings suggest remarkable stability of ependymal cell function and provide fundamental insights into the molecular signature of the V-SVZ niche.
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•High-fidelity genetic labeling and analysis of ependymal cells in the adult V-SVZ•Ependymal cells are transcriptionally distinct from neural stem cells•Ependymal cells express cilia genes (e.g., FoxJ1), not angiogenic genes (e.g., Flt1)•Ependymal cells don’t behave as neural stem cells or progenitors in vitro or in vivo
Targeted labeling of ependymal cells in a transgenic mouse model provides insights into the molecular signature of the ventricular-subventricular zone niche but is not consistent with ependymal cell neurogenic capacity at that site.
Dermal fibroblasts exhibit considerable heterogeneity during homeostasis and in response to injury. Defining lineage origins of reparative fibroblasts and regulatory programs that drive fibrosis or, ...conversely, promote regeneration will be essential for improving healing outcomes. Using complementary fate-mapping approaches, we show that hair follicle mesenchymal progenitors make limited contributions to wound repair. In contrast, extrafollicular progenitors marked by the quiescence-associated factor Hic1 generated the bulk of reparative fibroblasts and exhibited functional divergence, mediating regeneration in the center of the wound neodermis and scar formation in the periphery. Single-cell RNA-seq revealed unique transcriptional, regulatory, and epithelial-mesenchymal crosstalk signatures that enabled mesenchymal competence for regeneration. Integration with scATAC-seq highlighted changes in chromatin accessibility within regeneration-associated loci. Finally, pharmacological modulation of RUNX1 and retinoic acid signaling or genetic deletion of Hic1 within wound-activated fibroblasts was sufficient to modulate healing outcomes, suggesting that reparative fibroblasts have latent but modifiable regenerative capacity.
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•Hair follicle (HF) dermal stem cells make minor contributions to skin and HF neogenesis•Extrafollicular Hic1+ progenitors regenerate injured dermis and populate neogenic HFs•Distinct transcriptional and epigenetic changes mediate fibroblast heterogeneity•Runx1, retinoic acid, and Hic1 control mesenchymal regenerative competence
Abbasi et al. show that interfollicular (but not hair follicle-associated) mesenchymal progenitors generate the bulk of reparative fibroblasts in skin wounds. Wound microenvironments remodel the regulatory landscape of recruited fibroblasts, resulting in regeneration centrally and scar-formation peripherally. Pharmacogenetic modulation of regeneration-associated regulators within wound-activated fibroblasts modifies healing outcomes.
Skin aging is accompanied by hair loss due to impairments in hair follicle (HF) epithelial progenitor cells and their mesenchymal niche. This inductive mesenchyme, called dermal papilla (DP), ...undergoes progressive cell loss and eventual miniaturization that contributes to HF pathogenesis. Using laser ablation and fate mapping, we show that HF dermal stem cells (hfDSCs) reconstitute the damaged DP and maintain hair growth, suggesting that hfDSC dysfunction may trigger degeneration of the inductive niche. Fate mapping over 24 months revealed progressive hfDSC depletion, and in vivo clonal analysis of aged hfDSCs showed impaired self-renewal and biased differentiation. Single-cell RNA-seq confirmed hfDSCs as a central precursor, giving rise to divergent mesenchymal trajectories. In aged skin, hfDSCs exhibited senescent-like characteristics, and senescence-associated secretory phenotypes were identified in the aging HF mesenchyme. These results clarify fibroblast dynamics within the HF and suggest that progressive dysfunction within the mesenchymal progenitor pool contributes to age-related hair loss.
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•In vivo ablation of anagen DP cells initiates activation and repopulation by hfDSCs•Single-cell RNA-seq reveals dysfunction of aged HF mesenchyme and progressive loss•hfDSCs are seconded to replenish the DP cells in aged HFs•Aging causes hfDSC dysfunction and depletion of the progenitor pool
Shin et al. demonstrate that HF mesenchymal progenitors become dysfunctional with advanced age and are unable to repopulate the DP. This progenitor dysfunction leads to a net loss of inductive mesenchymal cells within each HF, consequently contributing to progressive hair loss.
Abstract
An MIL-100 (Fe)/graphene oxide (GO) hybrid, a fairly-known composite, was made through a simple one-step procedure and played a highlighted role in the photo-induced oxidative ...functionalization of the benzylic C–H bond. To identify the given binary composite, various techniques were applied: FT-IR, P-XRD, SEM, nitrogen absorption–desorption analysis, TGA, TEM, and UV–Visible DRS spectra. Proportions of GO used within the structure of the prepared composite differently ranged from low to high amount, and the most optimized ratio met at 38.5% of GO as the most efficient catalyst. Additionally, the reaction ran in Glycerol/K
2
CO
3
(2:1) as the optimal solvent. The elemental roles of O
2
·
−
and OH
−
were supposed to be the major ones for running a tandem oxidation-Knoevenagel reaction. The heterogeneity and reusability of the catalyst were also examined and confirmed after five successive runs.
In mammalian testis, contractile peritubular myoid cells (PMCs) regulate the transport of sperm and luminal fluid, while secreting growth factors and extracellular matrix proteins to support the ...spermatogonial stem cell niche. However, little is known about the role of testicular smooth muscle cells during postnatal testicular development. Here we report age-dependent expression of hypermethylated in cancer 1 (
; also known as
) in testicular smooth muscle cells, including PMCs and vascular smooth muscle cells, in the mouse. Postnatal deletion of
in smooth muscle cells led to their increased proliferation and resulted in dilatation of seminiferous tubules, with increased numbers of PMCs. These seminiferous tubules contained fewer Sertoli cells and more spermatogonia, and fibronectin was not detected in their basement membrane. The expression levels of genes encoding smooth muscle contractile proteins,
and
, were downregulated in the smooth muscle cells lacking
, and the seminiferous tubules appeared to have reduced contractility. These data imply a role for
in determining the size of seminiferous tubules by regulating postnatal smooth muscle cell proliferation, subsequently affecting spermatogenesis in adulthood.
Plasmonic nanostructures can be used to tackle the shortcomings of conventional photosensitizers in photodynamic therapy (PDT) of cancers, including their low reactive oxygen species (ROS) quantum ...yield, stability, and targetability. However, the positive role of plasmonic nanostructures is not limited to their ability for ROS generation or singlet oxygen formation. The main advantage of plasmonic nanostructures relies on the collective oscillation of free electrons, the so-called surface plasmon resonance (SPR), which can trigger plenty of optical phenomena in their near-field. Surface plasmon resonance is highly dependent on the morphology, size, and composition of the plasmonic nanostructure, which can give one the ability to control the wavelength of light-matter interaction, which is highly desirable in PDT applications. This review has focused on the conjugation of plasmonic nanostructures with organic compounds, biological compounds, ceramic nanoparticles, polymeric nanoparticles, metal-organic frameworks (MOFs), and magnetic nanoparticles from a mechanistic point of view. Hybridization of plasmonic nanoparticles would enable plenty of optical mechanisms beneficial for the PDT process that has been extensively discussed by presenting the most recent efforts in each category. This review can be a useful guideline for researchers working on enhancing the efficiency of the PDT process and those interested in plasmon-enhanced phenomena by emphasizing the underlying mechanisms.
Plasmonic nanoparticles are hybridized with organic compounds, biological compounds, ceramic nanoparticles, metal-organic frameworks, and magnetic nanoparticles as a new class of nano-photosensitizers for cancer treatment.
K2CO3/Glycerin as a deep eutectic solvent (DES) was anchored covalently onto functionalized magnetic nanoparticles and showed a significant activity towards the oxidation of various alcohols under ...mild conditions with a short reaction time and good to high yield. A combination of the magnetic nanoparticles and deep eutectic solvent offers a novel, green, reusable catalyst with easy separation. Also, the catalyst structure was well characterized using techniques such as FT‐IR spectroscopy, XRD, SEM, TGA, BET, VSM, TEM, and energy‐dispersive X‐ray spectroscopy (EDS).
K2CO3/Glycerine as a deep eutectic solvent was anchored covalently onto magnetic Fe3O4@SiO2 core‐shell nanoparticles. This heterogeneous catalyst was effectively used for the selective oxidation of alcohols to corresponding carbonyl products with up to 95 % yields.
The adult hair follicle (HF) undergoes successive regeneration driven by resident epithelial stem cells and neighboring mesenchyme. Recent work described the existence of HF dermal stem cells ...(hfDSCs), but the genetic regulation of hfDSCs and their daughter cell lineages in HF regeneration remains unknown. Here we prospectively isolate functionally distinct mesenchymal compartment in the HF (dermal cup DC; includes hfDSCs and dermal papilla) and define the transcriptional programs involved in hfDSC function and acquisition of divergent mesenchymal fates. From this, we demonstrate cross-compartment mesenchymal signaling within the HF niche, whereby DP-derived R-spondins act to stimulate proliferation of both hfDSCs and epithelial progenitors during HF regeneration. Our findings describe unique transcriptional programs that underlie the functional heterogeneity among specialized fibroblasts within the adult HF and identify a novel regulator of mesenchymal progenitor function during tissue regeneration.
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•Transcriptional compartmentalization of the hair follicle mesenchyme•Hair follicle dermal stem cells (hfDSCs) exhibit a unique gene expression profile•DP-derived R-spondins coordinately activate hfDSCs and epithelial progenitors•Gene expression profiling of hair follicle dermal stem cells
Biological Sciences; Developmental Biology; Stem Cells Research
The dermal papilla (DP) is one of two principal mesenchymal compartments of the hair follicle (HF). We previously reported that a population of HF dermal stem cells (hfDSCs) function to regenerate ...the dermal sheath (DS), but intriguingly also contribute new cells to the adult DP at the onset of anagen hair growth to maintain normal cycling of HFs and support the production of large hair fibres. Here, we asked whether injury altered the behaviour of hfDSCs and their progeny in order to support wound‐induced hair growth (WIHG) and if the response was modulated by hair cycle stage. αSMACreERT2:ROSAYFP mice received tamoxifen to label the DS, including hfDSCs. Full‐thickness excisions were made on the dorsal skin during various stages of the hair cycle. The skin was harvested at the subsequent anagen. Interestingly, there was an increase in the magnitude of recruitment of hfDSC progeny into the DP after injury compared to follicles entering natural second anagen. This bias towards a DP fate only occurred when a wound was induced during certain stages of the HC. In summary, injury modifies the fate of hfDSCs progeny, biasing them towards recruitment into the DP, with the hair cycle stage also influencing this response.
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