Predicting Blood Pressures for Pregnant Women by PPG and Personalized Deep Learning.

Blood pressure (BP) is predicted by this effort based on photoplethysmography (PPG) data to provide effective pre-warning of possible preeclampsia of pregnant women. Towards frequent BP measurement, a PPG sensor device is utilized in this study as a solution to offer continuous, cuffless blood pressure monitoring frequently for pregnant women. PPG data were collected using a flexible sensor patch from the wrist arteries of 194 subjects, which included 154 normal individuals and 40 pregnant women. Deep-learning models in 3 stages were built and trained to predict BP. The first stage involves developing a baseline deep-learning BP model using a dataset from common subjects. In the 2nd stage, this model was fine-tuned with data from pregnant women, using a 1-Dimensional Convolutional Neural Network (1D-CNN) with Convolutional Block Attention Module (CBAMs), followed by bi-directional Gated Recurrent Units (GRUs) layers and attention layers. The fine-tuned model results in a mean error (ME) of -1.40 ± 7.15 (standard deviation, SD) for systolic blood pressure (SBP) and -0.44 (ME) ± 5.06 (SD) for diastolic blood pressure (DBP). At the final stage is the personalization for individual pregnant women using transfer learning again, enhancing further the model accuracy to -0.17 (ME) ± 1.45 (SD) for SBP and 0.27 (ME) ± 0.64 (SD) for DBP showing a promising solution for continuous, non-invasive BP monitoring in precision by the proposed 3-stage of modeling, fine-tuning and personalization.

The dataset of the effects of fly ash on growth and yield of radish plant under two types of soil.

This article presents data of the effects of fly ash on growth and yield of radish plant under two types of soil (delta clay rich soil and coastal sandy soil). The experiment was conducted under semi-controlled conditions in a greenhouse at the Faculty of Agronomy, Vietnam National University of Agriculture (latitude 21°0'01N, longitude 105° 9'32″ W). The experiment has been conducted with the Randomized Complete Block Design (RCBD), each experimental formula was repeated 5 times. A total of 10 experimental formulas were performed including 100% delta clay rich soil, 95% delta clay rich soil+5% FA, 90% delta clay rich soil+10% FA, 85% delta clay rich soil+15% FA, 80% delta clay rich soil+20% FA, 100% coastal sandy soil, 95% coastal sandy soil+5%FA, 90% coastal sandy soil +10%FA, 85% coastal sandy soil+15%FA, and 80% coastal sandy soil+20%FA. Data on germination rate, plant height, number of leaves, SPAD values, leaf area, shoot fresh and dry weight, storage-root traits, storage-root fresh and dry weight were collected to assess the effects of fly ash on growth and yield of radish plant under delta clay rich soil and coastal sandy soil. This data could help develop a strategy fly ash application for crop cultivation.

Mesenteric Parametrial Fat Pad Surgery for in vivo Implantation of Hepatocytes in Nude Mice.

Cell-based liver therapies utilizing functionally stabilized engineered hepatic tissue hold promise in improving host liver functions and are emerging as a potential alternative to whole-organ transplantation. Owing to the ability to accommodate a large ex vivo engineered hepatocyte mass and dense vascularization, the mesenteric parametrial fat pad in female nude mice forms an ideal anatomic microenvironment for ectopic hepatocyte transplantation. However, the lack of any reported protocol detailing the presurgical preparation and construction of the engineered hepatic hydrogel, fat pad surgery, and postsurgical care and bioluminescence imaging to confirm in vivo hepatocyte implantation makes it challenging to reliably perform and test engraftment and integration with the host. In this report, we provide a step-by-step protocol for in vivo hepatocyte implantation, including preparation of hepatic tissue for implantation, the surgery process, and bioluminescence imaging to assess survival of functional hepatocytes. This will be a valuable protocol for researchers in the fields of tissue engineering, transplantation, and regenerative medicine. Key features • Primary human hepatocytes transduced ex vivo with a lentiviral vector carrying firefly luciferase are surgically implanted onto the fat pad. • Bioluminescence helps monitor survival of transplanted hepatic tissue over time. • Applicable for assessment of graft survival, graft-host integration, and liver regeneration.

A 3D biomimetic model of lymphatics reveals cell-cell junction tightening and lymphedema via a cytokine-induced ROCK2/JAM-A complex.

Impaired lymphatic drainage and lymphedema are major morbidities whose mechanisms have remained obscure. To study lymphatic drainage and its impairment, we engineered a microfluidic culture model of lymphatic vessels draining interstitial fluid. This lymphatic drainage-on-chip revealed that inflammatory cytokines that are known to disrupt blood vessel junctions instead tightened lymphatic cell-cell junctions and impeded lymphatic drainage. This opposing response was further demonstrated when inhibition of rho-associated protein kinase (ROCK) was found to normalize fluid drainage under cytokine challenge by simultaneously loosening lymphatic junctions and tightening blood vessel junctions. Studies also revealed a previously undescribed shift in ROCK isoforms in lymphatic endothelial cells, wherein a ROCK2/junctional adhesion molecule-A (JAM-A) complex emerges that is responsible for the cytokine-induced lymphatic junction zippering. To validate these in vitro findings, we further demonstrated in a genetic mouse model that lymphatic-specific knockout of ROCK2 reversed lymphedema in vivo. These studies provide a unique platform to generate interstitial fluid pressure and measure the drainage of interstitial fluid into lymphatics and reveal a previously unappreciated ROCK2-mediated mechanism in regulating lymphatic drainage.

On-Chip Monolithically Integrated Ultraviolet Low-Threshold Plasmonic Metal-Semiconductor Heterojunction Nanolasers.

The metal-semiconductor heterojunction is imperative for the realization of electrically driven nanolasers for chip-level platforms. Progress in developing such nanolasers has hitherto rarely been realized, however, because of their complexity in heterojunction fabrication and the need to use noble metals that are incompatible with microelectronic manufacturing. Most plasmonic nanolasers lase either above a high threshold (101 -103 MW cm-2 ) or at a cryogenic temperature, and lasing is possible only after they are removed from the substrate to avoid the large ohmic loss and the low modal reflectivity, making monolithic fabrication impossible. Here, for the first time, record-low-threshold, room-temperature ultraviolet (UV) lasing of plasmon-coupled core-shell nanowires that are directly grown on silicon is demonstrated. The naturally formed core-shell metal-semiconductor heterostructure of the nanowires leads to a 100-fold improvement in growth density over previous results. This unprecedentedly high nanowire density creates intense plasmonic resonance, which is outcoupled to the resonant Fabry-Pérot microcavity. By boosting the emission strength by a factor of 100, the hybrid photonic-plasmonic system successfully facilitates a record-low laser threshold of 12 kW cm-2 with a spontaneous emission coupling factor as high as ≈0.32 in the 340-360 nm range. Such architecture is simple and cost-competitive for future UV sources in silicon integration.

A novel phosphorylation site involved in dissociating RAF kinase from the scaffolding protein 14-3-3 and disrupting RAF dimerization.

Rapidly accelerated fibrosarcoma (ARAF, BRAF, CRAF) kinase is central to the MAPK pathway (RAS-RAF-MEK-ERK). Inactive RAF kinase is believed to be monomeric, autoinhibited, and cytosolic, while activated RAF is recruited to the membrane via RAS-GTP, leading to the relief of autoinhibition, phosphorylation of key regulatory sites, and dimerization of RAF protomers. Although it is well known that active and inactive BRAF have differential phosphorylation sites that play a crucial role in regulating BRAF, key details are still missing. In this study, we report the characterization of a novel phosphorylation site, BRAFS732 (equivalent in CRAFS624), located in proximity to the C-terminus binding motif for the 14-3-3 scaffolding protein. At the C terminus, 14-3-3 binds to BRAFpS729 (CRAFpS621) and enhances RAF dimerization. We conducted mutational analysis of BRAFS732A/E and CRAFS624A/E and revealed that the phosphomimetic S→E mutant decreases 14-3-3 association and RAF dimerization. In normal cell signaling, dimerized RAF phosphorylates MEK1/2, which is observed in the phospho-deficient S→A mutant. Our results suggest that phosphorylation and dephosphorylation of this site fine-tune the association of 14-3-3 and RAF dimerization, ultimately impacting MEK phosphorylation. We further characterized the BRAF homodimer and BRAF:CRAF heterodimer and identified a correlation between phosphorylation of this site with drug sensitivity. Our work reveals a novel negative regulatory role for phosphorylation of BRAFS732 and CRAFS624 in decreasing 14-3-3 association, dimerization, and MEK phosphorylation. These findings provide insight into the regulation of the MAPK pathway and may have implications for cancers driven by mutations in the pathway.

Adenosine deaminase 2 produced by infiltrative monocytes promotes liver fibrosis in nonalcoholic fatty liver disease.

Elevated circulating activity of adenosine deaminase 2 (ADA2) is associated with liver fibrosis in nonalcoholic fatty liver disease (NAFLD). In the liver of NAFLD patients, ADA2-positive portal macrophages are significantly associated with the degree of liver fibrosis. These liver macrophages are CD14- and CD16-positive and co-express chemokine receptors CCR2, CCR5, and CXCR3, indicating infiltrative monocyte origin. Human circulatory monocytes release ADA2 upon macrophage differentiation in vitro. When stimulated by recombinant human ADA2 (rhADA2), human monocyte-derived macrophages demonstrate upregulation of pro-inflammatory and pro-fibrotic genes, including PDGF-B, a key pro-fibrotic cytokine. This PDGF-B upregulation is reproduced by inosine, the enzymatic product of ADA2, but not adenosine, and is abolished by E359N, a loss-of-function mutation in ADA2. Finally, rhADA2 also stimulates PDGF-B production from Kupffer cells in primary human liver spheroids. Together, these data suggest that infiltrative monocytes promote fibrogenesis in NAFLD via ADA2-mediated autocrine/paracrine signaling culminating in enhanced PDGF-B production.

Cell and Tissue Therapy for the Treatment of Chronic Liver Disease.

Liver disease is an important clinical problem, impacting 600 million people worldwide. It is the 11th-leading cause of death in the world. Despite constant improvement in treatment and diagnostics, the aging population and accumulated risk factors led to increased morbidity due to nonalcoholic fatty liver disease and steatohepatitis. Liver transplantation, first established in the 1960s, is the second-most-common solid organ transplantation and is the gold standard for the treatment of liver failure. However, less than 10% of the global need for liver transplantation is met at the current rates of transplantation due to the paucity of available organs. Cell- and tissue-based therapies present an alternative to organ transplantation. This review surveys the approaches and tools that have been developed, discusses the distinctive challenges that exist for cell- and tissue-based therapies, and examines the future directions of regenerative therapies for the treatment of liver disease.

Ultralow-Threshold Continuous-Wave Room-Temperature Crystal-Fiber/Nanoperovskite Hybrid Lasers for All-Optical Photonic Integration.

Continuous-wave (CW) room-temperature (RT) laser operation with low energy consumption is an ultimate goal for electrically driven lasers. A monolithically integrated perovskite laser in a chip-level fiber scheme is ideal. However, because of the well-recognized air and thermal instabilities of perovskites, laser action in a perovskite has mostly been limited to either pulsed or cryogenic-temperature operations. Most CW laser operations at RT have had poor durability. Here, crystal fibers that have robust and high-heat-load nature are shown to be the key to enabling the first demonstration of ultralow-threshold CW RT laser action in a compact, monolithic, and inexpensive crystal fiber/nanoperovskite hybrid architecture that is directly pumped with a 405 nm diode laser. Purcell-enhanced light-matter coupling between the atomically smooth fiber microcavity and the perovskite nanocrystallites gain medium enables a high Q (≈1500) and a high ß (0.31). This 762 nm laser outperforms previously reported structures with a record-low threshold of 132 nW and an optical-to-optical slope conversion efficiency of 2.93%, and it delivers a stable output for CW and RT operation. These results represent a significant advancement toward monolithic all-optical integration.

Pluripotent stem cell-derived epithelium misidentified as brain microvascular endothelium requires ETS factors to acquire vascular fate.

Cells derived from pluripotent sources in vitro must resemble those found in vivo as closely as possible at both transcriptional and functional levels in order to be a useful tool for studying diseases and developing therapeutics. Recently, differentiation of human pluripotent stem cells (hPSCs) into brain microvascular endothelial cells (ECs) with blood-brain barrier (BBB)-like properties has been reported. These cells have since been used as a robust in vitro BBB model for drug delivery and mechanistic understanding of neurological diseases. However, the precise cellular identity of these induced brain microvascular endothelial cells (iBMECs) has not been well described. Employing a comprehensive transcriptomic metaanalysis of previously published hPSC-derived cells validated by physiological assays, we demonstrate that iBMECs lack functional attributes of ECs since they are deficient in vascular lineage genes while expressing clusters of genes related to the neuroectodermal epithelial lineage (Epi-iBMEC). Overexpression of key endothelial ETS transcription factors (ETV2, ERG, and FLI1) reprograms Epi-iBMECs into authentic endothelial cells that are congruent with bona fide endothelium at both transcriptomic as well as some functional levels. This approach could eventually be used to develop a robust human BBB model in vitro that resembles the human brain EC in vivo for functional studies and drug discovery.

Fabrication of RHA-silica/graphene oxide nanocomposites for removal of lead ions from water.

In this study, rice husk ash-silica/graphene oxide (RHA-SiO2/GO) nanocomposites were synthesized by the in situ method using (3-aminopropyl) triethoxysilane as a coupling agent. The obtained products were used to remove lead ions (Pb2+) from aqueous solution. Effects of SiO2:GO mass ratio, contact time, pH and initial Pb2+ concentration on the adsorption capacity were studied. It was found that the suitable ratio of SiO2:GO for Pb2+ adsorption is 100:2. The suitable RHA-SiO2/GO was characterized by Fourier-transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, Brunauer-Emmett-Teller specific surface area and thermal gravimetric analysis. Accordingly, RHA-SiO2/GO nanocomposite could be used as promising adsorbent for the removal of Pb2+ from water.

Identification of SARS-CoV-2 inhibitors using lung and colonic organoids.

There is an urgent need to create novel models using human disease-relevant cells to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) biology and to facilitate drug screening. Here, as SARS-CoV-2 primarily infects the respiratory tract, we developed a lung organoid model using human pluripotent stem cells (hPSC-LOs). The hPSC-LOs (particularly alveolar type-II-like cells) are permissive to SARS-CoV-2 infection, and showed robust induction of chemokines following SARS-CoV-2 infection, similar to what is seen in patients with COVID-19. Nearly 25% of these patients also have gastrointestinal manifestations, which are associated with worse COVID-19 outcomes1. We therefore also generated complementary hPSC-derived colonic organoids (hPSC-COs) to explore the response of colonic cells to SARS-CoV-2 infection. We found that multiple colonic cell types, especially enterocytes, express ACE2 and are permissive to SARS-CoV-2 infection. Using hPSC-LOs, we performed a high-throughput screen of drugs approved by the FDA (US Food and Drug Administration) and identified entry inhibitors of SARS-CoV-2, including imatinib, mycophenolic acid and quinacrine dihydrochloride. Treatment at physiologically relevant levels of these drugs significantly inhibited SARS-CoV-2 infection of both hPSC-LOs and hPSC-COs. Together, these data demonstrate that hPSC-LOs and hPSC-COs infected by SARS-CoV-2 can serve as disease models to study SARS-CoV-2 infection and provide a valuable resource for drug screening to identify candidate COVID-19 therapeutics.

Adaptable haemodynamic endothelial cells for organogenesis and tumorigenesis.

Endothelial cells adopt tissue-specific characteristics to instruct organ development and regeneration1,2. This adaptability is lost in cultured adult endothelial cells, which do not vascularize tissues in an organotypic manner. Here, we show that transient reactivation of the embryonic-restricted ETS variant transcription factor 2 (ETV2)3 in mature human endothelial cells cultured in a serum-free three-dimensional matrix composed of a mixture of laminin, entactin and type-IV collagen (LEC matrix) 'resets' these endothelial cells to adaptable, vasculogenic cells, which form perfusable and plastic vascular plexi. Through chromatin remodelling, ETV2 induces tubulogenic pathways, including the activation of RAP1, which promotes the formation of durable lumens4,5. In three-dimensional matrices-which do not have the constraints of bioprinted scaffolds-the 'reset' vascular endothelial cells (R-VECs) self-assemble into stable, multilayered and branching vascular networks within scalable microfluidic chambers, which are capable of transporting human blood. In vivo, R-VECs implanted subcutaneously in mice self-organize into durable pericyte-coated vessels that functionally anastomose to the host circulation and exhibit long-lasting patterning, with no evidence of malformations or angiomas. R-VECs directly interact with cells within three-dimensional co-cultured organoids, removing the need for the restrictive synthetic semipermeable membranes that are required for organ-on-chip systems, therefore providing a physiological platform for vascularization, which we call 'Organ-On-VascularNet'. R-VECs enable perfusion of glucose-responsive insulin-secreting human pancreatic islets, vascularize decellularized rat intestines and arborize healthy or cancerous human colon organoids. Using single-cell RNA sequencing and epigenetic profiling, we demonstrate that R-VECs establish an adaptive vascular niche that differentially adjusts and conforms to organoids and tumoroids in a tissue-specific manner. Our Organ-On-VascularNet model will permit metabolic, immunological and physiochemical studies and screens to decipher the crosstalk between organotypic endothelial cells and parenchymal cells for identification of determinants of endothelial cell heterogeneity, and could lead to advances in therapeutic organ repair and tumour targeting.

A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids.

SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes respiratory failure but involves other organ systems including gut, liver, heart, and pancreas. We present an experimental platform comprised of cell and organoid derivatives from human pluripotent stem cells (hPSCs). A Spike-enabled pseudo-entry virus infects pancreatic endocrine cells, liver organoids, cardiomyocytes, and dopaminergic neurons. Recent clinical studies show a strong association with COVID-19 and diabetes. We find that human pancreatic beta cells and liver organoids are highly permissive to SARS-CoV-2 infection, further validated using adult primary human islets and adult hepatocyte and cholangiocyte organoids. SARS-CoV-2 infection caused striking expression of chemokines, as also seen in primary human COVID-19 pulmonary autopsy samples. hPSC-derived cells/organoids provide valuable models for understanding the cellular responses of human tissues to SARS-CoV-2 infection and for disease modeling of COVID-19.

A biomimetic pancreatic cancer on-chip reveals endothelial ablation via ALK7 signaling.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, lethal malignancy that invades adjacent vasculatures and spreads to distant sites before clinical detection. Although invasion into the peripancreatic vasculature is one of the hallmarks of PDAC, paradoxically, PDAC tumors also exhibit hypovascularity. How PDAC tumors become hypovascular is poorly understood. We describe an organotypic PDAC-on-a-chip culture model that emulates vascular invasion and tumor-blood vessel interactions to better understand PDAC-vascular interactions. The model features a 3D matrix containing juxtaposed PDAC and perfusable endothelial lumens. PDAC cells invaded through intervening matrix, into vessel lumen, and ablated the endothelial cells, leaving behind tumor-filled luminal structures. Endothelial ablation was also observed in in vivo PDAC models. We also identified the activin-ALK7 pathway as a mediator of endothelial ablation by PDAC. This tumor-on-a-chip model provides an important in vitro platform for investigating the process of PDAC-driven endothelial ablation and may provide a mechanism for tumor hypovascularity.

Cdc42 regulates branching in angiogenic sprouting in vitro.

OBJECTIVES: The morphogenetic events that occur during angiogenic sprouting involve several members of the Rho family of GTPases, including Cdc42. However, the precise roles of Cdc42 in angiogenic sprouting have been difficult to elucidate owing to the lack of models to study these events in vitro. Here, we aim to identify the roles of Cdc42 in branching morphogenesis in angiogenesis. METHODS: Using a 3D biomimetic model of angiogenesis in vitro, where endothelial cells were seeded inside a cylindrical channel within collagen gel and sprouted from the channel in response to a defined biochemical gradient of angiogenic factors, we inhibited Cdc42 activity with a small molecule inhibitor ML141 and examined the effects of Cdc42 on the morphogenetic processes of angiogenic sprouting. RESULTS: We find that partial inhibition of Cdc42 had minimal effects on directional migration of endothelial cells, but led to fewer branching events without affecting the length of these branches. We also observed that antagonizing Cdc42 reduced collective migration in favor of single cell migration. Additionally, Cdc42 also regulated the initiation of filopodial extensions in endothelial tip cells. CONCLUSIONS: Our findings suggest that Cdc42 can affect multiple morphogenetic processes during angiogenic sprouting and ultimately impact the architecture of the vasculature.

Screening and Production of Manganese Peroxidase from Fusarium sp. on Residue Materials

In this study, we report the manganese peroxidase production ability from a Fusarium sp. strain using an inexpensive medium of agriculture residues of either rice straw or wood chips as carbon source. The highest manganese peroxidase activity on rice straw medium and on wood chips was 1.76 U/mL by day 9 and 1.91 U/mL by day 12, respectively.

Atomically smooth hybrid crystalline-core glass-clad fibers for low-loss broadband wave guiding.

We demonstrate direct evidence for the first realization of atomically smooth sapphire crystalline fiber cores with a surface variation of only ~1.9 Å. The hybrid glass-clad crystalline cores were grown by a laser-based fiber drawing technique. Because of the improvement in crystal fiber quality, we were able, for the first time, to comprehensively and quantitatively elucidate the correlation between fiber nanostructure and optical loss. We also experimentally demonstrated that high-temperature treatment has a significant impact on defect relaxation and promotes excellent crystallinity, and hence enables low-loss optical wave guiding. The experimentally measured propagation losses in the order of 0.01-0.1 dB/cm are the lowest ever reported among conventional Ti:sapphire channel waveguides and ultrafast-laser-inscribed waveguides, and agree well with the theory. Through experiments and numerical calculation, we have demonstrated that low threshold and high efficiency of Ti:sapphire crystal fiber lasers are possible with the atomic-level roughness, low-loss propagation, and high crystallinity of the Ti:sapphire crystalline core.

Ligand-Driven and Full-Color-Tunable Fiber Source: Toward Next-Generation Clinic Fiber-Endoscope Tomography with Cellular Resolution.

In many biomedical applications, broad full-color emission is important, especially for wavelengths below 450 nm, which are difficult to cover via supercontinuum generation. Single-crystalline-core sapphires with defect-driven emissions have potential roles in the development of next-generation broadband light sources because their defect centers demonstrate multiple emission bands with tailored ligand fields. However, the inability to realize high quantum yields with high crystallinity by conventional methods hinders the applicability of ultra-broadband emissions. Here, we present how an effective one-step fiber-drawing process, followed by a simple and controllable thermal treatment, enables a low-loss, full-color, and crystal fiber-based generation with substantial color variability. The broad spectrum extends from 330 nm, which is over 50 nm further into the UV region than that in previously reported results. The predicted submicrometer spatial resolutions demonstrate that the defect-ligand fields are potentially beneficial for achieving in vivo cellular tomography. It is also noteworthy that the efficiency of the milliwatt-level full-color generation, with an optical-to-optical efficiency of nearly 5%, is the highest among that of the existing active waveguide schemes. In addition, direct evidence from high-resolution transmission electron microscopy together with electron energy loss spectroscopy and crystal-field ligands reveals an excellent crystalline core, atomically defined core/cladding interfacial roughness, and significant enhancements in new laser-induced electronic defect levels. Our work suggests an inexpensive, facile, and highly scalable route toward achieving cellular-resolution tomographic imaging and represents an important step in the development of endoscope-compatible diagnostic devices.

Lgr5+ cells regenerate hair cells via proliferation and direct transdifferentiation in damaged neonatal mouse utricle.

Recruitment of endogenous progenitors is critical during tissue repair. The inner ear utricle requires mechanosensory hair cells (HCs) to detect linear acceleration. After damage, non-mammalian utricles regenerate HCs via both proliferation and direct transdifferentiation. In adult mammals, limited transdifferentiation from unidentified progenitors occurs to regenerate extrastriolar Type II HCs. Here we show that HC damage in neonatal mouse utricle activates the Wnt target gene Lgr5 in striolar supporting cells. Lineage tracing and time-lapse microscopy reveal that Lgr5+ cells transdifferentiate into HC-like cells in vitro. In contrast to adults, HC ablation in neonatal utricles in vivo recruits Lgr5+ cells to regenerate striolar HCs through mitotic and transdifferentiation pathways. Both Type I and II HCs are regenerated, and regenerated HCs display stereocilia and synapses. Lastly, stabilized ß-catenin in Lgr5+ cells enhances mitotic activity and HC regeneration. Thus Lgr5 marks Wnt-regulated, damage-activated HC progenitors and may help uncover factors driving mammalian HC regeneration.