Application of Slice Culture System for Successional Dental Lamina in Diphyodont Mammals.

Replacement teeth develop from the successional dental lamina (SDL). Understanding how SDL transitions from quiescence to initiation is crucial for preserving dental lamina stem cells in the jawbone microenvironment and for complete tooth regeneration. Miniature pigs are good models for studying human tooth replacement because of their similarities to humans. However, the molecular mechanisms and cellular composition that initiate SDL development remain unclear. One possible reason for this is the limitations of the current methods for culturing SDL in vitro, such as the inability to directly observe tooth morphological changes during culture and low tissue viability. This study aimed to improve the in vitro culture method for SDL. Using a McIlwain Tissue Chopper, we obtained mandibular slices containing deciduous canine and SDL of permanent canine. The slices were approximately 500 µm thick and were cultured on a Transwell membrane supported with metal grids over medium. The SDL developed into the bud stage on the second day and entered the cap stage on the fifth day in vitro. The expression of proliferation markers, cell death markers, and key odontogenetic genes in vitro was similar to that observed in vivo. In conclusion, we successfully applied a slice culture system to the SDL of miniature pigs. This slice culture method allowed us to directly visualize SDL initiation and further elucidate the molecular mechanisms underlying the initiation of permanent tooth development.

Halide Anions Tuning of Lead-Free Perovskite-Type Ferroelectric Semiconductors with Inverse High-Temperature Symmetry Breaking.

There is a noticeable gap in the literature regarding research on halogen-substitution-regulated ferroelectric semiconductors featuring multiple phase transitions. Here, a new category of 1D perovskite ferroelectrics (DFP)2 SbX5 (DFP+ = 3,3-difluoropyrrolidium, X- = I- , Br- , abbreviated as I-1 and Br-2) with twophase transitions (PTs) is reported. The first low-temperature PT is a mmmFmm2 ferroelectric PT, while the high-temperature PT is a counterintuitive inverse temperature symmetry-breaking PT. By the substitution of iodine with bromine, the Curie temperature (Tc) significantly increases from 348 K of I-1 to 374 K of Br-2. Their ferroelectricity and pyroelectricity are improved (Ps value from 1.3 to 4.0 µC cm-2 , pe value from 0.2 to 0.48 µC cm-2  K-1 for I-1 and Br-2), while their optical bandgaps increased from 2.1 to 2.7 eV. A critical slowing down phenomenon is observed in the dielectric measurement of I-1 while Br-2 exhibits the ferroelastic domain. Structural and computational analyses elucidate that the order-disorder movement of cations and the distortion of the chain perovskite [SbX5 ]2- anions skeleton lead to PT. The semiconductor properties are determined by [SbX5 ]2- anions. The findings contribute to the development of ferroelectric semiconductors and materials with multiple PTs and provide materials for potential applications in the optoelectronic field.

The oligodontia phenotype in a X-linked hypohidrotic ectodermal dysplasia patient with a novel EVC2 variant.

Objectives: To analyse the pathogenic genes in a patient with hypohidrotic ectodermal dysplasia (HED) and explore the relationship between pathogenic genes and the oligodontia phenotype. Methods: Clinical data and peripheral blood were collected from a patient with HED. Pathogenic genes were analysed by whole-exon sequencing (WES) and verified by Singer sequencing. The secondary and tertiary structures of the variant proteins were predicted to analyse their toxicity. Results: The patient exhibited a severe oligodontia phenotype, wherein only two deciduous canines were left in the upper jaw. WES revealed a hemizygous EDA variant c.466C > T p.(Arg156Cys) and a novel heterozygous EVC2 variant c.1772T > C p.(Leu591Ser). Prediction of the secondary and tertiary structures of the EDA variant p.(Arg156Cys) and EVC2 variant p.(Leu591Ser) indicated impaired function of both molecules. Conclusion: The patient demonstrated a more severe oligodontia phenotype when compared with the other patients caused by the EDA variant c.466C > T. Since Evc2 is a positive regulator of the Sonic Hedgehog (Shh) signal pathway, we speculated that the EVC2 variant p.(Leu591Ser) may play a synergistic role in the oligodontia phenotype of HED, thereby exacerbating the oligodontia phenotype. Knowledge of oligodontia caused by multiple gene variants is of great significance for understanding individual differences in oligodontia phenotypes.

Compound heterozygous WNT10A missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia.

BACKGROUND: The aim of this study was to analyse the differences in the phenotypes of missing teeth between a pair of brothers with hypohidrotic ectodermal dysplasia (HED) and to investigate the underlying mechanism by comparing the mutated gene loci between the brothers with whole-exome sequencing. METHODS: The clinical data of the patients and their mother were collected, and genomic DNA was extracted from peripheral blood samples. By Whole-exome sequencing filtered for a minor allele frequency (MAF) ≤0.05 non-synonymous single-nucleotide variations and insertions/deletions variations in genes previously associated with tooth agenesis, and variations considered as potentially pathogenic were assessed by SIFT, Polyphen-2, CADD and ACMG. Sanger sequencing was performed to detect gene variations. The secondary and tertiary structures of the mutated proteins were predicted by PsiPred 4.0 and AlphaFold 2. RESULTS: Both brothers were clinically diagnosed with HED, but the younger brother had more teeth than the elder brother. An EDA variation (c.878 T > G) was identified in both brothers. Additionally, compound heterozygous variations of WNT10A (c.511C > T and c.637G > A) were identified in the elder brother. Digenic variations in EDA (c.878 T > G) and WNT10A (c.511C > T and c.637G > A) in the same patient have not been reported previously. The secondary structure of the variant WNT10A protein showed changes in the number and position of α-helices and ß-folds compared to the wild-type protein. The tertiary structure of the WNT10A variant and molecular simulation docking showed that the site and direction where WNT10A binds to FZD5 was changed. CONCLUSIONS: Compound heterozygous WNT10A missense variations may exacerbate the number of missing teeth in HED caused by EDA variation.

Supershear Rayleigh wave imaging for quantitative assessment of biomechanical properties of brain using air-coupled optical coherence elastography.

Recently, supershear Rayleigh waves (SRWs) have been proposed to characterize the biomechanical properties of soft tissues. The SRWs propagate along the surface of the medium, unlike surface Rayleigh waves, SRWs propagate faster than bulk shear waves. However, their behavior and application in biological tissues is still elusive. In brain tissue elastography, shear waves combined with magnetic resonance elastography or ultrasound elastography are generally used to quantify the shear modulus, but high spatial resolution elasticity assessment in 10 µm scale is still improving. Here, we develop an air-coupled ultrasonic transducer for noncontact excitation of SRWs and Rayleigh waves in brain tissue, use optical coherent elastography (OCE) to detect, and reconstruct the SRW propagation process; in combing with a derived theoretical model of SRWs on a free boundary surface, we quantify the shear modulus of brain tissue with high spatial resolution. We first complete validation experiments using a homogeneous isotropic agar phantom, and the experimental results clearly show the SRW is 1.9649 times faster than the bulk shear waves. Furthermore, the propagation velocity of SRWs in both the frontal and parietal lobe regions of the brain is all 1.87 times faster than the bulk shear wave velocity. Finally, we evaluated the anisotropy in different brain regions, and the medulla oblongata region had the highest anisotropy index. Our study shows that the OCE system using the SRW model is a new potential approach for high-resolution assessment of the biomechanical properties of brain tissue.

Enhanced Electrocaloric Effect of Lead Scandium Tantalate by Zirconium Doping.

The electrocaloric effect (ECE) is a novel technology that offers high efficiency and environmental friendliness, making it suitable for solid-state refrigeration applications. Among the extensively studied ECE materials, lead scandium tantalate (PST) stands out for its excellent performance. However, its applications are restricted by its narrow working temperature range. To overcome this limitation, we explore the enhancement of the ECE through zirconium ion doping. We synthesized PbSc0.5-0.5xTa0.5-0.5xZrxO3 samples (x = 0, 0.025, 0.05, 0.075). The introduction of zirconium ions led to an increase in the Curie temperature from 28.9 °C (x = 0) to 55.5 °C (x = 0.075). Additionally, the relaxation factor γ of the ceramics increased from 1.40 (x = 0) to 1.59 (x = 0.075). The temperature span (Tspan) exhibited a rising trend with increasing x, reaching 10.9 K at x = 0.075. The maximum temperature change (ΔTmax) was observed at x = 0.025, with a value of 1.94 K. X-ray diffraction (XRD) patterns revealed that zirconium ion doping influenced the B-site ordering degree, thereby regulating the ECE. To further validate the results, we employed direct measurements and thermodynamic calculations. Overall, the regulation of ionic ordering through zirconium doping effectively enhances the ECE performance. These findings contribute to the development of advanced materials for solid-state refrigeration technologies.

AKT from dental epithelium to papilla promotes odontoblast differentiation.

Epithelial-mesenchymal interactions occur during tooth development. The dental epithelium (DE) is regarded as the signal center that regulates tooth morphology. However, the mechanism by which DE regulates the differentiation of mesenchyme-derived dental papilla (DP) into odontoblasts remains unclear. Using miniature pigs as a model, we analyzed the expression profiles of the DE and DP during odontoblast differentiation using high-throughput RNA sequencing. The phosphatidylinositol-3-kinase (PI3K)/AKT pathway is one of the most enriched pathways in both DE and DP. The PI3K/AKT pathway was first activated in the inner enamel epithelium but not in the DP on embryonic day 50. This pathway was then activated in the odontoblast layer on embryonic day 60. We showed that AKT activation promoted odontoblast differentiation of DP cells. We further demonstrated that activation of PI3K/AKT signaling in the DE effectively increased the expression levels of AKT and dentin sialophosphoprotein in DP cells. Additionally, we found that DE cells secreted collagen type IV alpha 6 chain (COL4A6) downstream of epithelial AKT signaling to positively regulate mesenchymal AKT levels. Therefore, our data suggest that PI3K/AKT signaling from the DE to the DP promotes odontoblast differentiation via COL4A6 secretion.

Selenium-enriched Polysaccharides from Pyracantha fortuneana (SePFP) Ameliorated Hepatic Lipid Accumulation through Enhancing Mitochondrial Fatty Acid ß-Oxidation in Aging Mice.

Selenium-enriched polysaccharides from Pyracantha fortuneana (SePFP) has many beneficial physiological activities, but how it improves the aging associated abnormal lipid metabolism is still unclear. Therefore, we explored the mechanisms of the regulatory role of SePFP on liver lipid accumulation in aging mice. METHODS: 60 naturally aged C57BL/6J male mice were divided into 6 groups: adult group, aging group (21-month-old mice), aging mice treated with low-, medium- and high-doses of SePFP (SePFP-L, SePFP-M, SePFP-H), and aging mice treated with resveratrol (RSV). SePFP and RSV were administrated daily via oral gavage from 16 to 21 months old. The parameters of energy metabolism were measured in all mice before sacrifice, and liver tissues were collected to determine the levels of metabolism-related enzymes by real-time PCR and Western blot. RESULTS: We found that SePFP significantly reduced the body weight, liver to bodyweight ratio, and white fat to body weight ratio in aging mice. SePFP also down-regulated the triglycerides and cholesterol levels in liver and serum, and decreased respiratory quotient in aging mice. The mechanism of SePFP regulating lipid metabolism was mainly through promoting fatty acid transportation to mitochondria and enhancing mitochondrial ß-oxidation and ketone body production. CONCLUSION: SePFP attenuates liver lipid deposition in aging mice by enhancing hepatic mitochondrial ß-oxidation.

The expression of Runx2 in the pathogenesis of periodontitis.

OBJECTIVE: Runt-related transcription factor 2 (Runx2) plays an important role in bone metabolism; however, the relationship between Runx2 and periodontitis remains unclear. We investigated Runx2 expression in the gingiva of patients to explore its role in periodontitis. METHODS: Gingival samples of patients were collected, including healthy samples (control group) and periodontitis samples (P group). Periodontitis samples were divided into three groups based on the periodontitis stage. Samples with stage I and grade B periodontitis were in the P1 group, stage II and grade B in the P2 group, and stage III or IV and grade B in the P3 group. Immunohistochemistry and western blotting were performed to detect Runx2 levels. The probing (PD) and clinical attachment loss (CAL) were recorded. RESULTS: Runx2 expression levels in the P and P3 groups were higher than those in the control group. In addition, Runx2 expression was positively correlated with CAL and PD (r1 = 0.435, r2 = 0.396). CONCLUSION: The high expression level of Runx2 in the gingiva of patients with periodontitis may be correlated with the pathogenesis of periodontitis.

Novel acoustic radiation force optical coherence elastography based on ultrasmall ultrasound transducer for biomechanics evaluation of in vivo cornea.

We developed a novel acoustic radiation force optical coherence elastography (ARF-OCE) based on an ultrasmall ultrasound transducer for quantitative biomechanics evaluations of in vivo cornea. A custom single-sided meta-ultrasonic transducer with an outer diameter of 1.8 mm, focal spot diameter of 1.6 mm, central frequency of 930 kHz, and focal length of 0.8 mm was applied to excite the sample. The sample arm of the ARF-OCE system employed a three-dimensional printed holder that allowed for ultrasound excitation and ARF-OCE detection. The phase-resolved algorithm was combined with a Lamb wave model to depth-resolved evaluate corneal biomechanics after keratoconus and cross-linking treatments (CXL). The results showed that, compare to the healthy cornea, the Lamb wave velocity was significantly reduced in the keratoconus, increased in the cornea after CXL, and increased with cross-linked irradiation energy in the cornea. These results indicated the good clinical translation potential of the proposed novel ARF-OCE.

Modeling drug-induced liver injury and screening for anti-hepatofibrotic compounds using human PSC-derived organoids.

Preclinical models that can accurately predict the toxicity and efficacy of candidate drugs to human liver tissue are in urgent need. Human liver organoid (HLO) derived from human pluripotent stem cells offers a possible solution. Herein, we generated HLOs, and demonstrated the utility of these HLOs in modeling a diversity of phenotypes associated with drug-induced liver injury (DILI), including steatosis, fibrosis, and immune responses. Phenotypic changes in HLOs after treatment with tool compounds such as acetaminophen, fialuridine, methotrexate, or TAK-875 showed high concordance with human clinical data in drug safety testings. Moreover, HLOs were able to model liver fibrogenesis induced by TGFß or LPS treatment. We further devised a high-content analysis system, and established a high-throughput anti-fibrosis drug screening system using HLOs. SD208 and Imatinib were identified that can significantly suppress fibrogenesis induced by TGFß, LPS, or methotrexate. Taken together, our studies demonstrated the potential applications of HLOs in drug safety testing and anti-fibrotic drug screening.

Enhanced Superconductivity and Upper Critical Field in Ta-Doped Weyl Semimetal Td -MoTe2.

2D transition metal dichalcogenides are promising platforms for next-generation electronics and spintronics. The layered Weyl semimetal (W,Mo)Te2 series features structural phase transition, nonsaturated magnetoresistance, superconductivity, and exotic topological physics. However, the superconducting critical temperature of the bulk (W,Mo)Te2 remains ultralow without applying a high pressure. Here, the significantly enhanced superconductivity is observed with a transition temperature as large as about 7.5 K in bulk Mo1- x Tax Te2 single crystals upon Ta doping (0 ≤ x ≤ 0.22), which is attributed to an enrichment of density of states at the Fermi level. In addition, an enhanced perpendicular upper critical field of 14.5 T exceeding the Pauli limit is also observed in Td -phase Mo1- x Tax Te2 (x = 0.08), indicating the possible emergence of unconventional mixed singlet-triplet superconductivity owing to the inversion symmetry breaking. This work provides a new pathway for exploring the exotic superconductivity and topological physics in transition metal dichalcogenides.

Acute liver steatosis translationally controls the epigenetic regulator MIER1 to promote liver regeneration in a study with male mice.

The early phase lipid accumulation is essential for liver regeneration. However, whether this acute lipid accumulation can serve as signals to direct liver regeneration rather than simply providing building blocks for cell proliferation remains unclear. Through in vivo CRISPR screening, we identify MIER1 (mesoderm induction early response 1) as a key epigenetic regulator that bridges the acute lipid accumulation and cell cycle gene expression during liver regeneration in male animals. Physiologically, liver acute lipid accumulation induces the phosphorylation of EIF2S1(eukaryotic translation initiation factor 2), which consequently attenuated Mier1 translation. MIER1 downregulation in turn promotes cell cycle gene expression and regeneration through chromatin remodeling. Importantly, the lipids-EIF2S1-MIER1 pathway is impaired in animals with chronic liver steatosis; whereas MIER1 depletion significantly improves regeneration in these animals. Taken together, our studies identify an epigenetic mechanism by which the early phase lipid redistribution from adipose tissue to liver during regeneration impacts hepatocyte proliferation, and suggest a potential strategy to boost liver regeneration.

Lead-Free Hybrid Organic-Inorganic Ferroelectric: (3,3-Difluoropyrrolidinium)2ZnCl4·H2O.

Hybrid organic-inorganic ferroelectrics (HOIFs) have a wide range of applications in the optoelectronic field in terms of rich optoelectronic properties. Particularly, lead-free HOIFs have attracted extensive attention due to their environmental friendliness, low heavy metal toxicity, and low synthesis cost. However, there are few reports about Zn-based HOIFs due to their uncontrollable ferroelectric synthesis and other reasons. Here, we designed and synthesized a zinc-based zero-dimensional (3,3-difluoropyrrolidine)2ZnCl4·H2O (DFZC) single crystal, which undergoes a phase transition from ferroelectric to paraelectric phase (space group from Pna21 to Pnma) at 295.5 K/288.9 K during the heating/cooling process. The systematic study shows that the ferroelectric phase transition is a displacive type. The ferroelectric hysteresis loop of DFZC was obtained by the double-wave method and the Sawyer-Tower method, which has a spontaneous polarization (Ps) of ∼0.4 µC/cm2. This work reveals the strategy to design new zinc-based lead-free HOIFs for potential applications in optoelectronic fields.

MRG15 aggravates non-alcoholic steatohepatitis progression by regulating the mitochondrial proteolytic degradation of TUFM.

BACKGROUND & AIMS: How hepatic steatosis progresses to non-alcoholic steatohepatitis (NASH) is complicated and remains unclear. The mortality factor 4-like protein 1 (MORF4L1, also called MRG15) was previously identified as a master nuclear chromatin remodeler in the rhythmic regulation of lipid synthesis gene expression in the liver. Whether it also contributes to the progression from liver steatosis to NASH is unclear. METHODS: We adopted 2 different murine NASH models, liver biopsies from patients with NASH, and primary mouse and human hepatocyte cultures for functional examination of MRG15 in NASH progression. Immunoprecipitation-mass spectrometry was applied to identify protein partners of MRG15, and CRISPR targeting was used for gene depletion in liver cells in vivo. RESULTS: The MRG15 level is increased in the livers of humans and mice with NASH. The inflammatory cytokines in NASH livers stabilize MRG15 by increasing its acetylation. Considerable amounts of MRG15 associate with the outer mitochondrial membrane, where it interacts with and deacetylates the mitochondrial Tu translation elongation factor (TUFM). Deacetylated TUFM, especially at the K82 and K91 sites, is subjected to accelerated degradation by the mitochondrial ClpXP protease system. Reduced liver TUFM consequently results in impaired mitophagy, increased oxidative stress and activation of the NLRP3 inflammasome pathway. Blocking MRG15 expression protects the liver from NASH progression by increasing the stability of liver TUFM. Liver samples from patients with NASH also display a clear reduction in TUFM level, which correlates with increased MRG15 expression. CONCLUSION: Collectively, these findings uncover a mitochondrial MRG15-TUFM regulatory pathway that contributes significantly to progression from simple steatosis to NASH, and which could potentially be targeted to treat NASH. LAY SUMMARY: The incidence of non-alcoholic fatty liver disease and its progressive form non-alcoholic steatohepatitis (NASH) is increasing, posing a significant global health challenge. Herein, we have uncovered the importance of the MRG15-TUFM pathway in NASH development. This pathway is active in the mitochondria (energy powerhouse of the cell) and could be targeted for the treatment of NASH.

Study on the Aqueous CdTe Quantum Dots Solar Device Deposited by Blade Coating on Magnesium Zinc Oxide Window Layer.

Aqueous CdTe quantum dots solar cells have been successfully fabricated by the blade coating method on the magnesium zinc oxide (Zn1-xMgxO or ZMO) window layer. Compared with the ZMO mono-window layer, the ZMO/CdS bi-window layer can decrease the interface recombination effectively due to the lower lattice mismatch and fast interdiffusion between CdS and CdTe. Moreover, the high temperature annealing of the CdTe quantum dots absorbed layer passivates the grain boundary of the CdTe crystalline via the replacement reaction of tellurium with sulfur. Finally, the conversion efficiency of our aqueous CdTe quantum dots solar device is improved from 3.21% to 8.06% with the introduction of the CdS interlayer and high temperature CdCl2 annealing. Our aqueous CdTe quantum dots solar devices show a large open circuit voltage and fill factor which are comparable with the conventional devices that are fabricated with organic CdTe quantum dots. We believe that it is the spike-like conduction band alignment between the ZMO and CdTe absorbed layer that reduces the majority carrier concentration, leading to the decrease in interface recombination probability.

Spatiotemporal Expression Patterns of Critical Genes Involved in FGF Signaling During Morphogenesis and Odontogenesis of Deciduous Molars in Miniature Pigs.

The fibroblast growth factor (FGF) pathway plays an important role in epithelial-mesenchymal interactions during tooth development. Nevertheless, how the ligands, receptors, and antagonists of the FGF pathway are involved in epithelial-mesenchymal interactions remains largely unknown. Miniature pigs exhibit tooth anatomy and replacement patterns like those in humans and hence can serve as large animal models. The present study investigated the spatiotemporal expression patterns of critical genes encoding FGF ligands (FGF3, FGF4, FGF7, and FGF9), antagonists (SPRY2 and SPRY4) and receptors (FGFR1, FGFR2, and FGFR3) in the third deciduous molars of miniature pigs at the cap (embryonic day 40, E40), early bell (E50), and late bell (E60) stages. The results of in situ hybridization (ISH) with tyramide signal amplification and of qRT-PCR analysis revealed increased expression of FGF7, FGFR1, FGFR2, and SPRY4 in dental epithelium and of FGF7 and FGFR1 in mesenchyme from E40 to E50. In contrast, the results revealed decreased expression of FGF3, FGF4, FGF9, and FGFR3 in dental epithelium and of FGF4, FGF9, FGFR2, and FGFR3 in the mesenchyme from E40 to E60. Mesenchyme signals of FGF3, FGF4, FGF7, SPRY2, FGFR2, and FGFR3 were concentrated in the odontoblast layer from E50 to E60. The distinct expression patterns of these molecules indicated elaborate regulation during dental morphogenesis. Our results provide a foundation for further investigation into fine-tuning dental morphogenesis and odontogenesis by controlling interactions between dental epithelium and mesenchyme, thus promoting tooth regeneration in large mammals.

In Vivo Evaluation of the Effects of SMILE with Different Amounts of Stromal Ablation on Corneal Biomechanics by Optical Coherence Elastography.

This work aims to depth-resolved quantitatively analyze the effect of different stromal ablation amounts on the corneal biomechanical properties during small incision lenticule extraction (SMILE) using optical coherence elastography (OCE). A 4.5-MHz ultrasonic transducer was used to excite elastic waves in the corneal tissue. The OCE system combined with the antisymmetric Lamb wave model was employed to achieve a high-resolution, high-sensitivity, and depth-resolved quantitative detection of the corneal Young's modulus. Eighteen rabbits were randomly divided into three groups; each group had six rabbits. The first and second groups underwent -3D and -6D SMILE surgeries, and the third group was the control group, respectively. Young's modulus of the corneal cap and residual stromal bed (RSB) were both increased after SMILE, which shared the stress under intraocular pressure (IOP). Furthermore, the Young's modulus of both the corneal cap and RSB after 3D SMILE group were significantly lower than that in the -6D group, which indicated that the increases in the post-operative corneal Young's modulus were positively correlated with the amount of stromal ablation. The OCE system for quantitative spatial characterization of corneal biomechanical properties can provide useful information on the extent of safe ablation for SMILE procedures.

[Applications of stem cell disease models in liver metabolic research and drug development].

The high failure rate of the new drug development has been well recognized. Relying on the pre-clinical data obtained from animal experiments will inevitably cause a low concordance with human clinical trials, which will eventually lead to new drug development failure. Employing human induced pluripotent stem cells (iPSCs) or adult stem cells to simulate disease models can not only provide an unlimited cell materials, but also faithfully represent the genetic background of a certain disease, when iPSCs or adult stem cells derived from patients with a specific disease genetic variation are applied. In addition, gene editing methods can be used to introduce genetic variants of interest into stem cells to generate disease models. Furthermore, by establishing a cell bank with a population of iPSCs in petri dish, in vitro human genetic studies can be carried out in these cells, with GWAS and QTL studies applied to identify genetic variants that are associated with drug sensitivity or cytotoxicity. These efforts may offer valuable information for the recruitment of suitable patients for clinical trials. Therefore, stem cell-derived disease models can provide valuable resources for the pathophysiological studies of diseases as well as the drug development. In this review, we will briefly introduce the development of the liver disease models derived from stem cells and their applications in disease study and drug development.