Ptip safeguards the epigenetic control of skeletal stem cell quiescence and potency in skeletogenesis.

Stem cells remain in a quiescent state for long-term maintenance and preservation of potency; this process requires fine-tuning regulatory mechanisms. In this study, we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells (SSCs) in skeletogenesis governed by a key regulator, Ptip (also known as Paxip1, Pax interaction with transcription-activation domain protein-1). Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs, and loss of Ptip in type II collagen (Col2)+ progenitors causes abnormal activation and differentiation of SSCs, impaired growth plate morphogenesis, and long bone dysplasia. We also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1 (Pgk1) by repressing histone H3K27ac at the promoter region. Notably, inhibition of glycolysis improved the function of SSCs despite Ptip deficiency. To the best of our knowledge, this is the first study to establish an epigenetic framework based on Ptip, which safeguards skeletal stem cell quiescence and potency through metabolic control. This framework is expected to improve SSC-based treatments of bone developmental disorders.

CenhANCER: a comprehensive cancer enhancer database for primary tissues and cell lines.

Enhancers, which are key tumorigenic factors with wide applications for subtyping, diagnosis and treatment of cancer, are attracting increasing attention in the cancer research. However, systematic analysis of cancer enhancers poses a challenge due to the lack of integrative data resources, especially those from tumor primary tissues. To provide a comprehensive enhancer profile across cancer types, we developed a cancer enhancer database CenhANCER by curating public resources including all the public H3K27ac ChIP-Seq data from 805 primary tissue samples and 671 cell line samples across 41 cancer types. In total, 57 029 408 typical enhancers, 978 411 super-enhancers and 226 726 enriched transcription factors were identified. We annotated the super-enhancers with chromatin accessibility regions, cancer expression quantitative trait loci (eQTLs), genotype-tissue expression eQTLs and genome-wide association study risk single nucleotide polymorphisms (SNPs) for further functional analysis. The identified enhancers were highly consistent with accessible chromatin regions in the corresponding cancer types, and all the 10 super-enhancer regions identified from one colorectal cancer study were recapitulated in our CenhANCER, both of which testified the high quality of our data. CenhANCER with high-quality cancer enhancer candidates and transcription factors that are potential therapeutic targets across multiple cancer types provides a credible resource for single cancer analysis and for comparative studies of various cancer types. Database URL http://cenhancer.chenzxlab.cn/.

Ptip is essential for tooth development via regulating Wnt pathway.

OBJECTIVE: Epigenetic regulation plays important role in stem cell maintenance. Ptip was identified as epigenetic regulator, but the role in dental progenitor cells remains unclear. SUBJECTS AND METHODS: Dental mesenchymal progenitor cells were targeted by Sp7-icre and visualized in mTmG; Sp7-icre mice. The Ptipf/f ; Sp7-icre mice were generated and the phenotype of incisors and molars were shown by micro-computerized tomography, scanning electron microscope, hematoxylin & eosin staining, and immunofluorescence. Dental mesenchymal progenitor cells were sorted by fluorescence-activated cell sorting from lower incisors and RNA sequencing was performed. RESULTS: The Sp7-icre targets dental mesenchymal progenitor cells in incisors and molars. The Ptipf/f ; Sp7-icre mice showed spontaneous fractures in the cusp of upper incisors and lower incisors at 3 weeks (w), compensative overgrowth of lower incisors at 1 month (M), and overgrowth extended to the outside at 2 M. The molars showed shortened roots. The functions of odontoblasts and dental mesenchymal progenitor cells were impaired. Mechanically, loss of Ptip activates the Wnt pathway and upregulates the expression of Wls in dental mesenchymal progenitor cells. Also, the regenerative ability of lower incisors was significantly impaired. CONCLUSION: We first demonstrated that Ptip was crucial for tooth development via regulating Wnt signaling.

GenOrigin: A comprehensive protein-coding gene origination database on the evolutionary timescale of life.

The origination of new genes contributes to the biological diversity of life. New genes may quickly build their network, exert important functions, and generate novel phenotypes. Dating gene age and inferring the origination mechanisms of new genes, like primate-specific genes, is the basis for the functional study of the genes. However, no comprehensive resource of gene age estimates across species is available. Here, we systematically date the age of 9,102,113 protein-coding genes from 565 species in the Ensembl and Ensembl Genomes databases, including 82 bacteria, 57 protists, 134 fungi, 58 plants, 56 metazoa, and 178 vertebrates, using a protein-family-based pipeline with Wagner parsimony algorithm. We also collect gene age estimate data from other studies and uniformly distribute the gene age estimates to time ranges in a million years for comparison across studies. All the data are cataloged into GenOrigin (http://genorigin.chenzxlab.cn/), a user-friendly new database of gene age estimates, where users can browse gene age estimates by species, age, and gene ontology. In GenOrigin, the information such as gene age estimates, annotation, gene ontology, ortholog, and paralog, as well as detailed gene presence/absence views for gene age inference based on the species tree with evolutionary timescale, is provided to researchers for exploring gene functions.

An Improved 4H-SiC MESFET with a Partially Low Doped Channel.

An improved 4H-SiC metal semiconductor field effect transistor (MESFET) based on the double-recessed MESFET (DR-MESFET) for high power added efficiency (PAE) is designed and simulated in this paper and its mechanism is explored by co-simulation of ADS and ISE-TCAD software. This structure has a partially low doped channel (PLDC) under the gate, which increases the PAE of the device by decreasing the absolute value of the threshold voltage (Vt), gate-source capacitance (Cgs) and saturation current (Id). The simulated results show that with the increase of H, the PAE of the device increases and then decreases when the value of NPLDC is low enough. The doping concentration and thickness of the PLDC are respectively optimized to be NPLDC = 1 × 1015 cm-3 and H = 0.15 µm to obtain the best PAE. The maximum PAE obtained from the PLDC-MESFET is 43.67%, while the PAE of the DR-MESFET is 23.43%; the optimized PAE is increased by 86.38%.

Improved MRD 4H-SiC MESFET with High Power Added Efficiency.

An improved multi-recessed double-recessed p-buffer layer 4H-SiC metal semiconductor field effect transistor (IMRD 4H-SiC MESFET) with high power added efficiency is proposed and studied by co-simulation of advanced design system (ADS) and technology computer aided design (TCAD) Sentaurus software in this paper. Based on multi-recessed double-recessed p-buffer layer 4H-SiC metal semiconductor field effect transistor (MRD 4H-SiC MESFET), the recessed area of MRD MESFET on both sides of the gate is optimized, the direct current (DC), radio frequency (RF) parameters and efficiency of the device is balanced, and the IMRD MESFET with a best power-added efficiency (PAE) is finally obtained. The results show that the PAE of the IMRD MESFET is 68.33%, which is 28.66% higher than the MRD MESFET, and DC and RF performance have not dropped significantly. Compared with the MRD MESFET, the IMRD MESFET has a broader prospect in the field of microwave radio frequency.

Novel High-Energy-Efficiency AlGaN/GaN HEMT with High Gate and Multi-Recessed Buffer.

A novel AlGaN/GaN high-electron-mobility transistor (HEMT) with a high gate and a multi-recessed buffer (HGMRB) for high-energy-efficiency applications is proposed, and the mechanism of the device is investigated using technology computer aided design (TCAD) Sentaurus and advanced design system (ADS) simulations. The gate of the new structure is 5 nm higher than the barrier layer, and the buffer layer has two recessed regions in the buffer layer. The TCAD simulation results show that the maximum drain saturation current and transconductance of the HGMRB HEMT decreases slightly, but the breakdown voltage increases by 16.7%, while the gate-to-source capacitance decreases by 17%. The new structure has a better gain than the conventional HEMT. In radio frequency (RF) simulation, the results show that the HGMRB HEMT has 90.8%, 89.3%, and 84.4% power-added efficiency (PAE) at 600 MHz, 1.2 GHz, and 2.4 GHz, respectively, which ensures a large output power density. Overall, the results show that the HGMRB HEMT is a better prospect for high energy efficiency than the conventional HEMT.

Improved DRUS 4H-SiC MESFET with High Power Added Efficiency.

A 4H-SiC metal semiconductor field effect transistor (MESFET) with layered doping and undoped space regions (LDUS-MESFET) is proposed and simulated by ADS and ISE-TCAD software in this paper. The structure (LDUS-MESFET) introduced layered doping under the lower gate of the channel, while optimizing the thickness of the undoped region. Compared with the double-recessed 4H-SiC MESFET with partly undoped space region (DRUS-MESFET), the power added efficiency of the LDUS-MESFET is increased by 85.8%, and the saturation current is increased by 27.4%. Although the breakdown voltage of the device has decreased, the decrease is within an acceptable range. Meanwhile, the LDUS-MESFET has a smaller gate-source capacitance and a large transconductance. Therefore, the LDUS-MESFET can better balance DC and AC characteristics and improve power added efficiency (PAE).