High-Performance Multifunctional Carbon Fibrous Sponges Derived from Pitch.

3D carbon-based porous sponges are recognized for significant potential in oil absorption and electromagnetic interference (EMI). However, their widespread application is hindered by a common compromise between high performance and affordability of mass production. Herein, a novel approach is introduced that involves laser-assisted micro-zone heating melt-blown spinning (LMHMS) to address this challenge by creating pitch-based submicron carbon fibers (PSCFs) sponge with 3D interconnected structures. These structures bestow the resulting sponge exceptional characteristics including low density (≈20 mg cm-3), high porosity (≈99%), remarkable compressibility (80% maximum strain), and superior conductivity (≈628 S m-1). The resultant PSCF sponges realize an oil/organic solvent sorption capacity over 56 g/g and possess remarkable regenerated ability. In addition to their effectiveness in cleaning up oil/organic solvent spills, they also demonstrated strong electromagnetic shielding capabilities, with a total shielding effectiveness (SE) exceeding 60 dB across the X-band GHz range. In virtue of extreme lightweight of ≈20 mg cm-3, the specific SE of the PSCF sponge reaches as high as ≈1466 dB cm3 g-1, surpassing the performance of numerous carbon-based porous structures. Thus, the unique blend of properties renders these sponges promising for transforming strategies in addressing oil/organic solvent contaminations and providing effective protection against EMI.

MnO(001) thin films on MgO(001) grown by reactive MBE using supersonic molecular beams.

MnO(001) thin films were grown on commercial MgO(001) substrates at 520 °C by reactive molecular beam epitaxy (MBE) using Mn vapor and O2-seeded supersonic molecular beams (SMBs) both with and without radio frequency (RF) plasma excitation. For comparison, MnO(001) films were grown by reactive MBE using O2 from a leak valve. X-ray photoelectron spectroscopy confirmed the Mn2+ oxidation state and 10%-15% excess oxygen near the growth surface. Reflection high-energy electron diffraction and x-ray diffraction evidenced that the films were rock salt cubic MnO with very strong (001) orientation. High-angle annular dark field scanning transmission electron microscopy with energy-dispersive x-ray spectroscopy demonstrated abrupt MnO/MgO interfaces and indicated [(001)MnO||(001)MgO] epitaxial growth. Ex situ atomic force microscopy of films deposited without RF excitation revealed smooth growth surfaces. An SMB-grown MnO(001) film was converted to Mn3O4 with strong (110) orientation by post-growth exposure to an RF-discharge (RFD) SMB source providing O atoms; the surface of the resultant film contained elongated pits aligned with the MgO110 directions. In contrast, using the RFD-SMB source for growth resulted in MnO(001) films with elongated growth pits and square pyramidal hillocks aligned along the MgO110 and 100 directions, respectively.

Components of the phosphatidylserine endoplasmic reticulum to plasma membrane transport mechanism as targets for KRAS inhibition in pancreatic cancer.

KRAS is mutated in 90% of human pancreatic ductal adenocarcinomas (PDACs). To function, KRAS must localize to the plasma membrane (PM) via a C-terminal membrane anchor that specifically engages phosphatidylserine (PtdSer). This anchor-binding specificity renders KRAS-PM localization and signaling capacity critically dependent on PM PtdSer content. We now show that the PtdSer lipid transport proteins, ORP5 and ORP8, which are essential for maintaining PM PtdSer levels and hence KRAS PM localization, are required for KRAS oncogenesis. Knockdown of either protein, separately or simultaneously, abrogated growth of KRAS-mutant but not KRAS-wild-type pancreatic cancer cell xenografts. ORP5 or ORP8 knockout also abrogated tumor growth in an immune-competent orthotopic pancreatic cancer mouse model. Analysis of human datasets revealed that all components of this PtdSer transport mechanism, including the PM-localized EFR3A-PI4KIIIα complex that generates phosphatidylinositol-4-phosphate (PI4P), and endoplasmic reticulum (ER)-localized SAC1 phosphatase that hydrolyzes counter transported PI4P, are significantly up-regulated in pancreatic tumors compared to normal tissue. Taken together, these results support targeting PI4KIIIα in KRAS-mutant cancers to deplete the PM-to-ER PI4P gradient, reducing PM PtdSer content. We therefore repurposed the US Food and Drug Administration-approved hepatitis C antiviral agent, simeprevir, as a PI4KIIIα inhibitor In a PDAC setting. Simeprevir potently mislocalized KRAS from the PM, reduced the clonogenic potential of pancreatic cancer cell lines in vitro, and abrogated the growth of KRAS-dependent tumors in vivo with enhanced efficacy when combined with MAPK and PI3K inhibitors. We conclude that the cellular ER-to-PM PtdSer transport mechanism is essential for KRAS PM localization and oncogenesis and is accessible to therapeutic intervention.

riboviz 2: a flexible and robust ribosome profiling data analysis and visualization workflow.

MOTIVATION: Ribosome profiling, or Ribo-seq, is the state-of-the-art method for quantifying protein synthesis in living cells. Computational analysis of Ribo-seq data remains challenging due to the complexity of the procedure, as well as variations introduced for specific organisms or specialized analyses. RESULTS: We present riboviz 2, an updated riboviz package, for the comprehensive transcript-centric analysis and visualization of Ribo-seq data. riboviz 2 includes an analysis workflow built on the Nextflow workflow management system for end-to-end processing of Ribo-seq data. riboviz 2 has been extensively tested on diverse species and library preparation strategies, including multiplexed samples. riboviz 2 is flexible and uses open, documented file formats, allowing users to integrate new analyses with the pipeline. AVAILABILITY AND IMPLEMENTATION: riboviz 2 is freely available at github.com/riboviz/riboviz.

Anti-Inflammatory Activity of Panax notoginseng Flower Saponins Quantified Using LC/MS/MS.

Panax notoginseng (Burk) F. H. Chen is a traditional Chinese medicinal and edible plant. However, Panax notoginseng flower (PNF) is rarely used. Therefore, the purpose of this study was to explore the main saponins and the anti-inflammatory bioactivity of PNF saponins (PNFS). We explored the regulation of cyclooxygenase 2 (COX-2), a key mediator of inflammatory pathways, in human keratinocyte cells treated with PNFS. A cell model of UVB-irradiation-induced inflammation was established to determine the influence of PNFS on inflammatory factors and their relationship with LL-37 expression. An enzyme-linked immunosorbent assay and Western blotting analysis were used to detect the production of inflammatory factors and LL37. Finally, liquid chromatography-tandem mass spectrometry was employed to quantify the main active components (ginsenosides Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1, and notoginsenoside R1) in PNF. The results show that PNFS substantially inhibited COX-2 activity and downregulated the production of inflammatory factors, indicating that they can be used to reduce skin inflammation. PNFS also increased the expression of LL-37. The contents of ginsenosides Rb1, Rb2, Rb3, Rc, and Rd in PNF were much higher than those of Rg1, and notoginsenoside R1. This paper provides data in support of the application of PNF in cosmetics.

Arbitrary distance measurement without dead zone by chirped pulse spectrally interferometry using a femtosecond optical frequency comb.

We demonstrate an arbitrary distance measurement method by chirped pulse spectrally interferometry (CPSI) using femtosecond optical frequency comb (OFC). In this paper, the chirped fiber Bragg grating (CFBG) is used to investigate the mapping relationship between displacement and the center frequency of the chirped spectral interferogram. We overcome the direction ambiguity of dispersive interferometry (DPI) ranging and expand the range of distance measurement to 18 cm. Besides, we achieve a full range of dead-zone free ranging by introducing a variable optical delay line (VODL). And through principles simulation and experiment, it is demonstrated that the measurement accuracy is 12 µm in comparison with an incremental He-Ne laser interferometer and the minimum Allen deviation is 52 nm at an average time of 1.76 ms. Similarly, in the experiment with long-distance of ∼30m, the accuracy reaches 20 µm, and 2.51 µm repeatability is achieved under harsh environment.

Improvement of Distance Measurement Based on Dispersive Interferometry Using Femtosecond Optical Frequency Comb.

Since the dispersive interferometry (DPI) based on optical frequency combs (OFCs) was proposed, it has been widely used in absolute distance measurements with long-distance and high precision. However, it has a serious problem for the traditional DPI based on the mode-locked OFC. The error of measurements caused by using the fast Fourier transform (FFT) algorithm to process signals cannot be overcome, which is due to the non-uniform sampling intervals in the frequency domain of spectrometers. Therefore, in this paper, we propose a new mathematical model with a simple form of OFC to simulate and analyze various properties of the OFC and the principle of DPI. Moreover, we carry out an experimental verification, in which we adopt the Lomb-Scargle algorithm to improve the accuracy of measurements of DPI. The results show that the Lomb-Scargle algorithm can effectively reduce the error caused by the resolution, and the error of absolute distance measurement is less than 12 µm in the distance of 70 m based on the mode-locked OFC.

Precision and repeatability improvement in frequency-modulated continuous-wave velocity measurement based on the splitting of beat frequency signals.

The basic principle of frequency-modulated continuous-wave lidars is to measure the velocity of a moving object through the Doppler frequency shift phenomenon. However, the vibration generated by the moving object will cause the spectrum to broaden and the precision and repeatability of speed measurement to decrease. In this paper, we propose a speed measurement method based on H13C14N gas cell absorption peak splitting the sweep signal of a large bandwidth triangular wave modulated frequency laser. This method obtains the speed of a continuously moving target by re-splicing an accurately-split frequency sweep signal, which effectively solves the problem of simultaneous processing of excessive amounts of data when measuring the speed of a continuously moving target. At the same time, the H13C14N gas cell absorbs the spectra of specific wavelengths, which reduces the phase delay of the beat signal corresponding to the up- and down-scanning, thus reducing the signal spectrum broadening caused by frequency deviation, and improving the speed measurement resolution and range effectively. The experimental results show that for speeds of up to 30mm/s, the mean error was less than 23µm/s and the mean standard deviation was less than 61µm/s.

Blockade of Kv1.3 potassium channel inhibits CD8+ T cell-mediated neuroinflammation via PD-1/Blimp-1 signaling.

Kv1.3 potassium channel is considered as a target for the treatment of autoimmune diseases such as multiple sclerosis (MS), since Kv1.3 blockade suppresses memory T cell activation including cytotoxic CD8+ T cells. However, the underlying signaling pathway related to autoimmune CD8+ T cell inhibition by Kv1.3 channel in neuroinflammatory diseases remains unclear. We found that ImK, a selective Kv1.3 blocker, reduced auto-reactive CD8+ T cell infiltration in the spinal cords of experimental autoimmune encephalomyelitis (EAE) rats, an animal model of MS. ImK suppressed transcriptional factor Blimp-1 expression and reduced the cytotoxicity of CD8+ T cells on neuronal cells. Furthermore, ImK upregulated co-inhibitory molecule PD-1 to inhibit B lymphocyte-induced maturation protein (Blimp-1) in an IL-2 independent way. In addition, PD-1 inhibitor impaired the suppression of ImK on CD8+ T cells and accelerated EAE progression. Our study demonstrated a novel regulatory mechanism of Kv1.3 blockade on modulating CD8+ T cell differentiation through PD-1/Blimp-1 signaling. This work expands the understanding of Kv1.3 channel for modulating neuroinflammation.

Direct Pore-Level Visualization and Verification of In Situ Oil-in-Water Pickering Emulsification during Polymeric Nanogel Flooding for EOR in a Transparent Three-Dimensional Micromodel.

Different from inorganic nanoparticles, nanosized cross-linked polymeric nanoparticles (nanogels) have been demonstrated to generate more stable Pickering emulsions under harsh conditions for a long term owing to their inherent high hydrophilicity and surface energy. In both core and pore scales, the emulsions are found to be able to form in situ during the nanofluid flooding process for an enhanced oil recovery (EOR) process. Due to the limitation of direct visualization in core scale or deficient pore geometries built by two-dimensional micromodels, the in situ emulsification by nanofluids and emulsion transport are still not being well understood. In this work, we use a three-dimensional transparent porous medium to directly visualize the in situ emulsification during the nanogel flooding process for EOR after water flooding. By synthesizing the nanogel with a fluorescent dye, we find the nanogels adsorbed on the oil-water interface to lower the total interfacial energy and emulsify the large oil droplets into small Pickering oil-in-water emulsions. A potential mechanism for in situ emulsification by nanogels is proposed and discussed. After nanogel flooding, the emulsions trapped in pore throats and those in the effluents are all found encapsulated by the nanogels. After nanogel flooding under different flow rates, the sphericity and diameter changes of remaining oil droplets are quantitatively compared and analyzed using grouped boxplots. It is concluded that in situ emulsification happens during nanogel injection due to the reduction of interfacial tension, which helps to increase the oil recovery rate under different flow rates and pore geometries.

A Flexible, Robust, and Gel-Free Electroencephalogram Electrode for Noninvasive Brain-Computer Interfaces.

Brain-computer interfaces (BCIs) enable direct and near-instant communication between the brain and electronic devices. One of the biggest remaining challenges is to develop an effective noninvasive BCI that allows the recording electrodes to avoid hair on human skin without the inconveniences and complications of using a conductive gel. In this study, we developed a cost-effective, easily manufacturable, flexible, robust, and gel-free silver nanowire/polyvinyl butyral (PVB)/melamine sponge (AgPMS) electroencephalogram (EEG) electrode that circumvents problems with hair. Because of surface metallization by the silver nanowires (AgNWs), the sponge has a high conductivity of 917 S/m while its weight remains the same. The flexible sponge framework and self-locking AgNWs combine to give the new electrode remarkable mechanical stability (the conductivity remains unchanged after 10 000 cycles at 10% compression) and the ability to bypass hair. A BCI application based on steady-state visual evoked potential (SSVEP) measurements on hairless skin shows that the BCI accuracy of the new electrode (86%) is approximately the same as that of conventional electrodes supported by a conductive gel (88%). Most importantly, the performance of the AgPMS on hairy skin is not significantly reduced, which indicates that the new electrode can replace conventional electrodes for both hairless and hairy skin BCIs and other EEG applications.

Ectopic fibroblast growth factor receptor 1 promotes inflammation by promoting nuclear factor-κB signaling in prostate cancer cells.

Initiation of expression of fibroblast growth factor receptor 1 (FGFR1) concurrent with loss of FGFR2 expression is a well-documented event in the progression of prostate cancer (PCa). Although it is known that some FGFR isoforms confer advantages in cell proliferation and survival, the mechanism by which the subversion of different FGFR isoforms contributes to PCa progression is incompletely understood. Here, we report that fibroblast growth factor (FGF) promotes NF-κB signaling in PCa cells and that this increase is associated with FGFR1 expression. Disruption of FGFR1 kinase activity abrogated both FGF activity and NF-κB signaling in PCa cells. Of note, the three common signaling pathways downstream of FGFR1 kinase, extracellular signal-regulated kinase 1/2 (ERK1/2), phosphoinositide 3-kinase (PI3K/AKT), and phosphoinositide phospholipase Cγ (PLCγ), were not required for FGF-mediated NF-κB signaling. Instead, transforming growth factor ß-activating kinase 1 (TAK1), a central regulator of the NF-κB pathway, was required for FGFR1 to stimulate NF-κB signaling. Moreover, we found that FGFR1 promotes NF-κB signaling in PCa cells by reducing TAK1 degradation and thereby supporting sustained NF-κB activation. Consistently, Fgfr1 ablation in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model reduced inflammation in the tumor microenvironment. In contrast, activation of the FGFR1 kinase in the juxtaposition of chemical-induced dimerization (CID) and kinase 1 (JOCK1) mouse model increased inflammation. As inflammation plays an important role in PCa initiation and progression, these findings suggest that ectopically expressed FGFR1 promotes PCa progression, at least in part, by increasing inflammation in the tumor microenvironment.

Pharmacologically targeting the myristoylation of the scaffold protein FRS2α inhibits FGF/FGFR-mediated oncogenic signaling and tumor progression.

Fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling facilitates tumor initiation and progression. Although currently approved inhibitors of FGFR kinase have shown therapeutic benefit in clinical trials, overexpression or mutations of FGFRs eventually confer drug resistance and thereby abrogate the desired activity of kinase inhibitors in many cancer types. In this study, we report that loss of myristoylation of fibroblast growth factor receptor substrate 2 (FRS2α), a scaffold protein essential for FGFR signaling, inhibits FGF/FGFR-mediated oncogenic signaling and FGF10-induced tumorigenesis. Moreover, a previously synthesized myristoyl-CoA analog, B13, which targets the activity of N-myristoyltransferases, suppressed FRS2α myristoylation and decreased the phosphorylation with mild alteration of FRS2α localization at the cell membrane. B13 inhibited oncogenic signaling induced by WT FGFRs or their drug-resistant mutants (FGFRsDRM). B13 alone or in combination with an FGFR inhibitor suppressed FGF-induced WT FGFR- or FGFRDRM-initiated phosphoinositide 3-kinase (PI3K) activity or MAPK signaling, inducing cell cycle arrest and thereby inhibiting cell proliferation and migration in several cancer cell types. Finally, B13 significantly inhibited the growth of xenograft tumors without pathological toxicity to the liver, kidney, or lung in vivo In summary, our study suggests a possible therapeutic approach for inhibiting FGF/FGFR-mediated cancer progression and drug-resistant FGF/FGFR mutants.

Facile and High-Yield Replacement Reaction-Assisted Synthesis of Silver Dendrites by Jet for Conductive Ink.

Metallic dendrites with uniform morphology, high purity, and large yield remain challenging to synthesize. In this work, single-crystalline silver (Ag) dendrites with uniform morphology, high purity, and large yield are successfully synthesized by employing single replacement reaction between aqueous silver nitrate (AgNO3) and solid copper (Cu) by jet. The combined effect of diffusion-limited aggregation and the locally oriented attachment of Ag particles is responsible for the formation of silver dendrites under nonequilibrium conditions. Finally, the potential applications of as-synthesized silver dendrites are demonstrated by successfully preparing silver-based conductive ink for flexible electronics and wearable equipment. The conductive pattern exhibits resistivity of 7.2 µΩ·cm, showing good conductivity of the prepared conductive material. This facile and time-efficient synthetic route can be extended to synthesize other noble metal nanostructures with desired morphologies by adopting selective precursor salt concentrations and substrate metals with proper redox potentials.

Dietary sn-2 palmitic triacylglycerols reduced faecal lipids, calcium contents and altered lipid metabolism in Sprague-Dawley rats.

In this study, the impact of dietary sn-2 palmitic triacylglycerol (sn-2 PTAG) on faecal lipids, calcium excretion and lipid metabolic alternation was investigated in Sprague-Dawley (SD) rats fed with high-fat diet containing either palm olein (PO, sn-2 palmitic acid (PA) of 14.8%), sn-2 PTAG50 (sn-2 PA of 56.4%) or sn-2 PTAG70 (sn-2 PA of 72.4%), respectively. After 4-week feeding period, SD rats fed with sn-2 PTAGs showed reduced faecal soap fatty acids, neutral lipid and calcium excretion compared to those of PO-fed rats, whereas a significant difference was only observed for the sn-2 PTAG70-fed rats (p < .05). Moreover, dietary sn-2 PTAG70 also showed a significant effect on decreasing serum triacylglycerol (TAG) level, reducing perirenal adipocyte size and regulating lipid metabolism in small intestine and perirenal adipose tissue of SD rats. Significantly increased mRNA levels of genes involved in intestinal lipid anabolism as well as lipid catabolism were both observed in the sn-2 PTAG70-fed rats (p < .05). Meanwhile, dietary sn-2 PTAG70 also significantly up-regulated lipolysis, mitochondrial fatty acid oxidation and thermogenesis-related gene and protein levels in perirenal adipose tissue, which might be correlated with the reduced perirenal adipocyte size. Taken together, our findings indicated that sn-2 PTAG70 may have some beneficial effects on intestinal lipid utilisation and lipid metabolic activity for energy supply in visceral adipose tissue.

Type 2 Fibroblast Growth Factor Receptor Signaling Preserves Stemness and Prevents Differentiation of Prostate Stem Cells from the Basal Compartment.

Prostate stem cells (P-SCs) are capable of giving rise to all three lineages of prostate epithelial cells, which include basal, luminal, and neuroendocrine cells. Two types of P-SCs have been identified in both human and mouse adult prostates based on prostasphere or organoid cultures, cell lineage tracing, renal capsule implantation, and expression of luminal- and basal-specific proteins. The sphere-forming P-SCs are from the basal cell compartment that express P63, and are therefore designated as basal P-SCs (P-bSCs). Luminal P-SCs (P-lSCs) express luminal cytokeratins and Nkx3.1. Herein, we report that the type 2 FGF receptor (FGFR2) signaling axis is crucial for preserving stemness and preventing differentiation of P-bSCs. FGFR2 signaling mediated by FGFR substrate 2α (FRS2α) is indispensable for formation and maintenance of prostaspheres derived from P63(+) P-bSCs. Ablation of Fgfr2 in P63(+) cells in vitro causes the disintegration of prostaspheres. Ablation of Fgfr2 in vivo reduces the number of P63-expressing basal cells and enriches luminal cells. This suggests a basal stem cell-to-luminal cell differentiation. In addition, ablation of Fgfr2 in P63(+) cells causes defective postnatal development of the prostate. Therefore, the data indicate that FGFR2 signaling is critical for preserving stemness and preventing differentiation of P-bSCs.

Prostate Sphere-forming Stem Cells Are Derived from the P63-expressing Basal Compartment.

Prostate stem cells (P-SCs) are capable of giving rise to all three lineages of prostate epithelial cells, including basal, luminal, and neuroendocrine cells. Multiple methods have been used to identify P-SCs in adult prostates. These include in vivo renal capsule implantation of a single epithelial cell with urogenital mesenchymal cells, in vitro prostasphere and organoid cultures, and lineage tracing with castration-resistant Nkx3.1 expression (CARN), in conjunction with expression of cell type-specific markers. Both organoid culture and CARN tracing show the existence of P-SCs in the luminal compartment. Although prostasphere cells predominantly express basal cell-specific cytokeratin and P63, the lineage of prostasphere-forming cells in the P-SC hierarchy remains to be determined. Using lineage tracing with P63(CreERT2), we show here that the sphere-forming P-SCs are P63-expressing cells and reside in the basal compartment. Therefore we designate them as basal P-SCs (P-bSCs). P-bSCs are capable of differentiating into AR(+) and CK18(+) organoid cells, but organoid cells cannot form spheres. We also report that prostaspheres contain quiescent stem cells. Therefore, the results show that P-bSCs represent stem cells that are early in the hierarchy of overall prostate tissue stem cells. Understanding the contribution of the two types of P-SCs to prostate development and prostate cancer stem cells and how to manipulate them may open new avenues for control of prostate cancer progression and relapse.

Enhanced perovskite morphology and crystallinity for high performance perovskite solar cells using a porous hole transport layer from polystyrene nanospheres.

Organic-inorganic metal halide perovskites have led to remarkable advancements in emerging photovoltaics. The rapid increase in the power conversion efficiency (PCE) of PSCs has been mainly achieved by improving perovskite morphology and crystallinity. Herein, we report a simple and effective means to improve perovskite grain sizes using a porous hole transport layer (i.e. , PEDOT: PSS in this work). We used polystyrene nanospheres as a sacrificial template to fabricate the porous-PEDOT:PSS. The growth of the CH3NH3PbI3 perovskite film on the porous-PEDOT:PSS substrate yields a dramatic improvement in crystallinity and an enhancement in perovskite grain sizes. When the porous structure was applied as a hole transport layer in PSCs with planar heterojunction structures, the efficiency was significantly enhanced from 15.33% for the planar device to 17.32%. This simple method for enhancing perovskite morphology and crystallinity paves the way for its application to other device architectures for enhanced photovoltaic performance.

Type 1 fibroblast growth factor receptor in cranial neural crest cell-derived mesenchyme is required for palatogenesis.

Cleft palate is a common congenital birth defect. The fibroblast growth factor (FGF) family has been shown to be important for palatogenesis, which elicits the regulatory functions by activating the FGF receptor tyrosine kinase. Mutations in Fgf or Fgfr are associated with cleft palate. To date, most mechanistic studies on FGF signaling in palate development have focused on FGFR2 in the epithelium. Although Fgfr1 is expressed in the cranial neural crest (CNC)-derived palate mesenchyme and Fgfr1 mutations are associated with palate defects, how FGFR1 in palate mesenchyme regulates palatogenesis is not well understood. Here, we reported that by using Wnt1(Cre) to delete Fgfr1 in neural crest cells led to cleft palate, cleft lip, and other severe craniofacial defects. Detailed analyses revealed that loss-of-function mutations in Fgfr1 did not abrogate patterning of CNC cells in palate shelves. However, it upset cell signaling in the frontofacial areas, delayed cell proliferation in both epithelial and mesenchymal compartments, prevented palate shelf elevation, and compromised palate shelf fusion. This is the first report revealing how FGF signaling in CNC cells regulates palatogenesis.

Fibroblast growth factor signaling is essential for self-renewal of dental epithelial stem cells.

A constant supply of epithelial cells from dental epithelial stem cell (DESC) niches in the cervical loop (CL) enables mouse incisors to grow continuously throughout life. Elucidation of the cellular and molecular mechanisms underlying this unlimited growth potential is of broad interest for tooth regenerative therapies. Fibroblast growth factor (FGF) signaling is essential for the development of mouse incisors and for maintenance of the CL during prenatal development. However, how FGF signaling in DESCs controls the self-renewal and differentiation of the cells is not well understood. Herein, we report that FGF signaling is essential for self-renewal and the prevention of cell differentiation of DESCs in the CL as well as in DESC spheres. Inhibiting the FGF signaling pathway decreased proliferation and increased apoptosis of the cells in DESC spheres. Suppressing FGFR or its downstream signal transduction pathways diminished Lgr5-expressing cells in the CL and promoted cell differentiation both in DESC spheres and the CL. Furthermore, disruption of the FGF pathway abrogated Wnt signaling to promote Lgr5 expression in DESCs both in vitro and in vivo. This study sheds new light on understanding the mechanism by which the homeostasis, expansion, and differentiation of DESCs are regulated.