Complete Chloroplast Genomes of Four Oaks from the Section Cyclobalanopsis Improve the Phylogenetic Analysis and Understanding of Evolutionary Processes in the Genus Quercus.

Quercus is a valuable genus ecologically, economically, and culturally. They are keystone species in many ecosystems. Species delimitation and phylogenetic studies of this genus are difficult owing to frequent hybridization. With an increasing number of genetic resources, we will gain a deeper understanding of this genus. In the present study, we collected four Quercus section Cyclobalanopsis species (Q. poilanei, Q. helferiana, Q. camusiae, and Q. semiserrata) distributed in Southeast Asia and sequenced their complete genomes. Following analysis, we compared the results with those of other species in the genus Quercus. These four chloroplast genomes ranged from 160,784 bp (Q. poilanei) to 161,632 bp (Q. camusiae) in length, with an overall guanine and cytosine (GC) content of 36.9%. Their chloroplast genomic organization and order, as well as their GC content, were similar to those of other Quercus species. We identified seven regions with relatively high variability (rps16, ndhk, accD, ycf1, psbZ-trnG-GCC, rbcL-accD, and rpl32-trnL-UAG) which could potentially serve as plastid markers for further taxonomic and phylogenetic studies within Quercus. Our phylogenetic tree supported the idea that the genus Quercus forms two well-differentiated lineages (corresponding to the subgenera Quercus and Cerris). Of the three sections in the subgenus Cerris, the section Ilex was split into two clusters, each nested in the other two sections. Moreover, Q. camusiae and Q. semiserrata detected in this study diverged first in the section Cyclobalanopsis and mixed with Q. engleriana in the section Ilex. In particular, 11 protein coding genes (atpF, ndhA, ndhD, ndhF, ndhK, petB, petD, rbcL, rpl22, ycf1, and ycf3) were subjected to positive selection pressure. Overall, this study enriches the chloroplast genome resources of Quercus, which will facilitate further analyses of phylogenetic relationships in this ecologically important tree genus.

Adaptive divergence and genetic vulnerability of relict species under climate change: a case study of Pterocarya macroptera.

BACKGROUND AND AIMS: Understanding adaptive genetic variation and whether it can keep pace with predicted future climate change is critical in assessing the genetic vulnerability of species and developing conservation management strategies. The lack of information on adaptive genetic variation in relict species carrying abundant genetic resources hinders the assessment of genetic vulnerability. Using a landscape genomics approach, this study aimed to determine how adaptive genetic variation shapes population divergence and to predict the adaptive potential of Pterocarya macroptera (a vulnerable relict species in China) under future climate scenarios. METHODS: We applied restriction site-associated DNA sequencing (RAD-seq) to obtain 8244 single-nucleotide polymorphisms (SNPs) from 160 individuals across 28 populations. We examined the pattern of genetic diversity and divergence, and then identified outliers by genetic differentiation (FST) and genotype-environment association (GEA) methods. We further dissected the effect of geographical/environmental gradients on genetic variation. Finally, we predicted genetic vulnerability and adaptive risk under future climate scenarios. KEY RESULTS: We identified three genetic lineages within P. macroptera: the Qinling-Daba-Tianmu Mountains (QDT), Western Sichuan (WS) and Northwest Yunnan (NWY) lineages, which showed significant signals of isolation by distance (IBD) and isolation by environment (IBE). IBD and IBE explained 3.7-5.7 and 8.6-12.8 % of the genetic structure, respectively. The identified GEA SNP-related genes were involved in chemical defence and gene regulation and may exhibit higher genetic variation to adapt to the environment. Gradient forest analysis revealed that the genetic variation was mainly shaped by temperature-related variables, indicating its adaptation to local thermal environments. A limited adaptive potential was suggested by the high levels of genetic vulnerability in marginal populations. CONCLUSIONS: Environmental gradient mainly shaped the population differentiation of P. macroptera. Marginal populations may be at high risk of extinction, and thus proactive management measures, such as assisted gene flow, are required to ensure the survival of these populations.

Protectin Conjugates in Tissue Regeneration 1 Inhibits Macrophage Pyroptosis by Restricting NLRP3 Inflammasome Assembly to Mitigate Sepsis via the cAMP-PKA Pathway.

Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel anti-inflammatory and proresolving lipid mediator biosynthesized from docosahexaenoic acid. Excessive activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome and consequent pyroptosis are involved in diverse inflammatory diseases. However, how PCTR1 affects NLRP3 inflammasome activation and pyroptosis are still unclear. Here, we demonstrated that PCTR1 inhibited NLRP3 inflammasome activation and pyroptosis. These results show that PCTR1 dose-dependently inhibited gasdermin D cleavage in lipopolysaccharide (LPS)-primed murine primary macrophages upon nigericin stimulation. Additionally, PCTR1 treatment after LPS priming inhibited caspase-1 activation and subsequent mature interleukin-1ß release independent of the nuclear factor-kappa B pathway. PCTR1 exerted its inhibitory effects by blocking NLRP3-apoptosis-associated speck-like protein containing a CARD (ASC) interaction and ASC oligomerization, thereby restricting NLRP3 inflammasome assembly. However, the inhibitory effect of PCTR1 could be reversed by KH7 and H89, which are the inhibitors of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway. Moreover, PCTR1 treatment alleviated lung tissue damage and improved mouse survival in LPS-induced sepsis. Our study unveils the molecular mechanism of negative regulation of NLRP3 inflammasome activation and pyroptosis by a novel lipid mediator and suggests that PCTR1 may serve as a potential treatment option for NLRP3-inflammasome driven diseases.

Inhibition of neointimal hyperplasia in balloon-induced vascular injuries in a rat model by miR-22 loading Laponite hydrogels.

Percutaneous coronary intervention (PCI) is the mainstream treatment to widen narrowed or obstructed coronary arteries due to pathological conditions. However, the post-operational neointimal hyperplasia occurs because of endothelium denudation during surgical procedures and the following inflammation. MicroRNAs (miRs) are new therapeutics of great potential for cardiovascular diseases. However, miRs easily degrade in vivo. A vehicle that can maintain their bioactivities and extend their retention at the site of delivery is prerequisite for miRs to play their roles as therapeutic reagents. Here, we reported the use of the Laponite hydrogels to deliver miR-22 that are modulators of phenotypes of smooth muscle cells (SMCs). The Laponite hydrogels allow a homogenous distribution of miR-22 within the gels, which had the capacity to transfect SMCs in vitro. Upon the injection of the miR-22 incorporated in the Laponite hydrogels in vivo, miR-22 could be well retained surrounding arteries for at least 7 days. Moreover, the miR-22 loading Laponite hydrogels inhibited the neointimal formation, reduced the infiltration of the macrophages, and reversed the adverse vascular ECM remodeling after the balloon-induced vascular injuries by upregulation of miR-22 and downregulation of its target genes methyl-CpG binding protein 2 (MECP2). The application of the Laponite hydrogels for miR local delivery may offer a novel strategy to treat cardiovascular diseases.

Mir-22-incorporated polyelectrolyte coating prevents intima hyperplasia after balloon-induced vascular injury.

Drug-coated balloons (DCBs) offer potential to deliver drugs to treat coronary lesions but without leaving permanent implants behind. Paclitaxel and sirolimus are anti-proliferation drugs that are commonly used in commercially available DCBs. However, these drugs present significant cytotoxicity concern and low efficacy in vivo. Here, we use microRNA-22 (miR-22) as balloon loaded drugs and polyelectrolyte complexes (PECs) polyethyleneimine/polyacrylic acid (PEI/PAA) as balloon coatings to establish a new DCB system through the ultrasonic spray method. The PEI/PAA forms a stable and thin coating on the balloon, which resulted in a good transfer capacity to the vessel wall both in vitro and in vivo. miR-22 that could modulate smooth muscle cell (SMC) phenotype switching is incorporated into the PEI/PAA coating and shows a sustained release profile. The PEI/PAA/miR-22 coated balloon successfully inhibits intima hyperplasia after balloon-induced vascular injury in a rat model through decreasing proliferative SMCs via the miR-22-methyl-CpG binding protein 2 (MECP2) axis. Our findings indicate that balloons coated with PEI/PAA/miR-22 have great potential to be promising DCBs in the treatment of cardiovascular disease.

[Voluntary wheel running exercise regulates microglia polarization in hippocampus through STAT3 signal pathway to inhibit depression-like behavior induced by chronic stress in rats].

This paper was aimed to investigate the effect of voluntary wheel running exercise on depression-like behavior induced by chronic water immersion restraint stress (CWIRS) and the underlying mechanism. Sprague-Dawley (SD) rats received CWIRS to induce depression-like behavior and 4-week voluntary wheel running exercise. Meanwhile, the rats were treated with lipopolysaccharide (LPS) or STAT3 over-expression vector (pcDNA-STAT3) by intracerebroventricular injection. Behavioral tests were used to detect depression-like behavior. ELISA assay was used to detect levels of various inflammatory factors in the rat hippocampus. Western blot was used to detect protein expression levels of ionized calcium binding adaptor molecule 1 (Iba1), inducible nitric oxide synthase (iNOS), arginase 1 (Arg1), phosphorylated STAT3 (p-STAT3) and total STAT3 (t-STAT3). The results showed that, compared with stress group, stress + exercise group exhibited improved depression-like behavior, decreased interleukin-1ß (IL-1ß) and IL-6 levels, increased IL-4 and IL-10 levels, down-regulated Iba-1 and iNOS protein expression levels, up-regulated Arg1 protein expression level, and decreased p-STAT3/t-STAT3 ratio in hippocampal tissue. LPS reversed the improving effect of voluntary wheel running exercise on depression-like behavior in rats, and the over-expression of STAT3 reversed the promoting effects of voluntary wheel running on M2 polarization of microglial cells in rat hippocampus and depression-like behavior. These results suggest that voluntary wheel running ameliorates the depression-like behavior induced by CWIRS in rats, and the mechanism may be related to regulating hippocampal microglia polarization via STAT3 signaling pathway.

Historical Dynamics of Semi-Humid Evergreen Forests in the Southeast Himalaya Biodiversity Hotspot: A Case Study of the Quercus franchetii Complex (Fagaceae).

The Oligocene and Miocene are key periods in the formation of the modern topography and flora of East Asian and Indo-China. However, it is unclear how geological and climatic factors contributed to the high endemism and species richness of this region. The Quercus franchetii complex is widespread in the southeast Himalaya fringe and northern Indo-China with a long evolutionary history. It provides a unique proxy for studying the diversity pattern of evergreen woody lineages in this region since the Oligocene. In this study, we combined chloroplast (cpDNA) sequences, nuclear microsatellite loci (nSSRs), and species distribution modeling (SDM) to investigate the impacts of geological events on genetic diversity of the Q. franchetii complex. The results showed that the initial cpDNA haplotype divergence was estimated to occur during the middle Oligocene (30.7 Ma), which might have been raised by the tectonic activity at this episode to the Miocene. The nSSR results revealed two major groups of populations, the central Yunnan-Guizhou plateau (YGP) group and the peripheral distribution group when K = 2, in responding to the rapid YGP uplift during the late Miocene, which restricted gene flow between the populations in core and marginal areas. SDM analysis indicated that the distribution ranges of the Q. franchetii complex expanded northwards after the last glacial maximum, but the core distribution range in YGP was stable. Our results showed that the divergence of Q. franchetii complex is rooted in the mid-Oligocene. The early geological events during the Oligocene, and the late Miocene may play key roles to restrict seed-mediated gene flow among regions, but the pollen-mediated gene flow was less impacted. The uplifts of the YGP and the climate since LGM subsequently boosted the divergence of the populations in core and marginal areas.

Seed germination schedule and environmental context shaped the population genetic structure of subtropical evergreen oaks on the Yun-Gui Plateau, Southwest China.

The evergreen broadleaved forests (EBLFs) of Southwest China have a long-term stable environment and support a diverse flora, thus forming a global biodiversity hotspot. However, the key drivers that have shaped the genetic diversity patterns of species in these EBLFs are not well understood. Quercus delavayi, Q. schottkyana, and Q. kerrii are sympatric oak species with different seed biological traits that are typical for these EBLFs. This study combined multilocus phylogeography and ecological niche modeling to screen 33 Q. delavayi populations. Their population genetic structure was inferred in comparison with previous studies on Q. schottkyana and Q. kerrii. The seed germination traits of all three species were also investigated. cpDNAs showed a significant phylogeographic structure in Q. delavayi, which was not detected in Q. schottkyana or Q. kerrii. Quercus delavayi, Q. kerrii, and Q. schottkyana exhibited different pollen-to-seed migration ratios (r = 219, 117, and 22, respectively), which are linked to the germination schedules of acorns. The distributions of Q. delavayi and Q. schottkyana remained long-term stable since the last glacial maximum (LGM) with a similar nSSR genetic gradient change along latitude. Instead, Q. kerrii experienced a prominent range expansion since the LGM with genetic diversification between the East and the West of the Tanaka line due to environmental heterogeneity. These results identify seed traits and environmental heterogeneity as two key drivers that shape the population genetic structure of EBLF trees in Southwest China. These should be considered in regional forestry conservation and management.

Functional characterization of CEP250 variant identified in nonsyndromic retinitis pigmentosa.

Retinitis pigmentosa (RP) is the most common manifestation of inherited retinal diseases with high degree of genetic, allelic, and phenotypic heterogeneity. CEP250 encodes the C-Nap1 protein and has been associated with various retinal phenotypes. Here, we report the identification of a mutation (c.562C>T, p.R188*) in the CEP250 in a consanguineous family with nonsyndromic RP. To gain insights into the molecular pathomechanism underlying CEP250 defects and the functional relevance of CEP250 variants in humans, we conducted a functional characterization of CEP250 variant using a novel Cep250 knockin mouse line. Remarkably, the disruption of Cep250 resulted in severe impairment of retinal function and significant retinal morphological alterations. The homozygous knockin mice showed significantly reduced retinal thickness and ERG responses. This study not only broadens the spectrum of phenotypes associated with CEP250 mutations, but also, for the first time, elucidates the function of CEP250 in photoreceptors using a newly established animal model.

Slc7a14 Is Indispensable in Zebrafish Retinas.

Previous study has identified SLC7A14 as a new causative gene of retinitis pigmentosa (RP). However, the role of SLC7A14 has not been fully characterized. The goal of this study was to investigate the biological features of slc7a14 in zebrafish. To determine the expression of slc7a14 in developing zebrafish, we performed in situ hybridization (ISH) and quantitative real-time PCR. Morpholino knockdown and overexpression experiments were performed to study the role of slc7a14 in zebrafish retinas. Immunostaining was carried out to observe structural changes. Visual motor responses (VMR) and optokinetic responses (OKR) were analyzed to assess visual behaviors. Terminal deoxynucleotidyl transferase (dUTP) nick-end labeling (TUNEL) staining was performed to survey apoptotic retinal cells. We found that slc7a14 was highly expressed in neuronal tissues, including the brain, spinal cord and retina, and that the expression levels increased during early embryogenesis. Consistently, ISH showed a similar expression pattern. Knockdown of slc7a14 led to dose-dependent microphthalmia that was reversed by overexpression. The immunostaining results revealed that the rod-specific protein zpr-3 and the retinal pigment epithelium-specific protein zpr-2 (decreased to 44.48%) were significantly suppressed in the slc7a14-silenced morphants. Notably, visual behaviors (the VMR and the OKR) were severely impaired in the slc7a14-deficient morphant, especially the VMR OFF response. In addition, apoptotic cells were observed in the retina at 3 days post fertilization (dpf) and 5 dpf by TUNEL assay. Our results demonstrated that slc7a14 is essential for visually mediated behaviors in zebrafish. Temporary silencing of slc7a14 in larvae led to severe visual impairments, consistent with the manifestations observed in RP patients. Our findings provide further insights into the genetic mechanisms of RP predisposition caused by SLC7A14 mutations.

Versatile Genome Engineering Techniques Advance Human Ocular Disease Researches in Zebrafish.

Over recent decades, zebrafish has been established as a sophisticated vertebrate model for studying human ocular diseases due to its high fecundity, short generation time and genetic tractability. With the invention of morpholino (MO) technology, it became possible to study the genetic basis and relevant genes of ocular diseases in vivo. Many genes have been shown to be related to ocular diseases. However, the issue of specificity is the major concern in defining gene functions with MO technology. The emergence of the first- and second-generation genetic modification tools zinc-finger nucleases (ZFNs) and TAL effector nucleases (TALENs), respectively, eliminated the potential phenotypic risk induced by MOs. Nevertheless, the efficiency of these nucleases remained relatively low until the third technique, the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, was discovered. This review highlights the application of multiple genome engineering techniques, especially the CRISPR/Cas9 system, in the study of human ocular diseases in zebrafish.

Mutation of IPO13 causes recessive ocular coloboma, microphthalmia, and cataract.

Ocular coloboma is a developmental structural defect of the eye that often occurs as complex ocular anomalies. However, its genetic etiology remains largely unexplored. Here we report the identification of mutation (c.331C>T, p.R111C) in the IPO13 gene in a consanguineous family with ocular coloboma, microphthalmia, and cataract by a combination of whole-exome sequencing and homozygosity mapping. IPO13 encodes an importin-B family protein and has been proven to be associated with the pathogenesis of coloboma and microphthalmia. We found that Ipo13 was expressed in the cornea, sclera, lens, and retina in mice. Additionally, the mRNA expression level of Ipo13 decreased significantly in the patient compared with its expression in a healthy individual. Morpholino-oligonucleotide-induced knockdown of ipo13 in zebrafish caused dose-dependent microphthalmia and coloboma, which is highly similar to the ocular phenotypes in the patient. Moreover, both visual motor response and optokinetic response were impaired severely. Notably, these ocular phenotypes in ipo13-deficient zebrafish could be rescued remarkably by full-length ipo13 mRNA, suggesting that the phenotypes observed in zebrafish were due to insufficient ipo13 function. Altogether, our findings demonstrate, for the first time, a new role of IPO13 in eye morphogenesis and that loss of function of IPO13 could lead to ocular coloboma, microphthalmia, and cataract in humans and zebrafish.

Geographical isolation and environmental heterogeneity contribute to the spatial genetic patterns of Quercus kerrii (Fagaceae).

Southwest China is one of the major global biodiversity hotspots. The Tanaka line, extending within southwestern China from its northwest to its southeast, is an important biogeographical boundary between the Sino-Japanese and Sino-Himalayan floristic regions. Understanding the evolutionary history of the regional keystone species would assist with both reconstructing historical vegetation dynamics and ongoing biodiversity management. In this research, we combined phylogeographic methodologies and species distribution models (SDMs) to investigate the spatial genetic patterns and distribution dynamics of Quercus kerrii, a dominant evergreen oak inhabiting southwest China lowland evergreen-broadleaved forests (EBLFs). A total of 403 individuals were sampled from 44 populations throughout southwest China. SDMs and mismatch distribution analysis indicated that Q. kerrii has undergone northward expansion since the Last Glacial Maximum (LGM). Quantitative analysis revealed that the range expansion of Q. kerrii since the LGM exceeded that of the sympatric mid-elevation species Quercus schottkyana, likely owing to their contrasting distribution elevations and habitat availabilities. The historical climate change since the LGM and the latitude gradient of the region played an important role in shaping the genetic diversity of Q. kerrii. The genetic differentiation index and genetic distance surface of Q. kerrii populations east of the Tanaka line exceeded those to its west. The long-term geographic isolation and environmental heterogeneity between the two sides of the Tanaka line might increase species divergence patterns and local adaptation. This study provides new insights into the historical dynamics of subtropical EBLFs and the changing biota of southwest China.

Introgression Threatens the Genetic Diversity of Quercus austrocochinchinensis (Fagaceae), an Endangered Oak: A Case Inferred by Molecular Markers.

Natural introgression can cause negative effects where rare species experience genetic assimilation and invade by their abundant congeners. Quercus austrocochinchinensis and Q. kerrii (subgenus Cyclobalanopsis) are a pair of closely related species in the Indo-China area. Morphological intermediates of the two species have been reported in this region. In this study, we used AFLP, SSR and two key leaf morphological diagnostic traits to study the two Q. austrocochinchinensis populations, two pure Q. kerrii and two putative hybrid populations in China. Rates of individual admixture were examined using the Bayesian clustering programs STRUCTURE and NewHybrids, with no a priori species assignment. In total, we obtained 151 SSR alleles and 781 polymorphic loci of AFLP markers. Population differentiation inferred by SSR and AFLP was incoherent with recognized species boundaries. Bayesian admixture analyses and principal coordinate analysis identified more hybrids and backcrossed individuals than morphological intermediates in the populations. SSR inferred a wide genetic assimilation in Q. austrocochinchinensis, except for subpopulation D2 in the core area of Xi-Shuang-Ban-Na Nature Reserve (XSBN). However, AFLP recognized more Q. austrocochinchinensis purebreds than SSR. Analysis using NewHybrids on AFLP data indicated that these hybridized individuals were few F2 and predominantly backcrosses with both parental species. All these evidences indicate the formation of a hybrid swarm at XSBN where the two species co-exist. Both AFLP and SSR recognized that the core protected area of XSBN (D2) has a high percentage of Q. austrocochinchinensis purebreds and a unique germplasm. The Hainan population and the other subpopulations of XSBN of the species might have lost their genetic integrity. Our results revealed a clear genetic differentiation in the populations and subpopulations of Q. austrocochinchinensis and ongoing introgression between Q. austrocochinchinensis and Q. kerrii at the disturbed contact areas. Combining the results from genetic and morphological analyses, the conservation of subpopulation D2 should be prioritized. Conservation and restoration of the integrity of tropical ravine rainforest is an important long-term goal for the successful conservation of Q. austrocochinchinensis. The fine-scale landscape might play an essential role in shaping the spatial patterns of hybridization. Further studies are needed to evaluate these patterns and dynamics.

Draft Genome Sequence of Staphylococcus hominis BHG17 Isolated from Wild Bar-Headed Goose (Anser indicus) Feces.

Staphylococcus hominis belongs to a group of coagulase-negative staphylococci and is an opportunistic pathogen, usually found on the skin and mucous membranes. Studies involving S. hominis isolated from wild birds are scarce. Here, we report a 2.365-Mb draft genome sequence of S. hominis BHG17, isolated from the feces of a bar-headed goose.

Novel mutations in PDE6B causing human retinitis pigmentosa.

AIM: To identify the genetic defects of a Chinese patient with sporadic retinitis pigmentosa (RP). METHODS: Ophthalmologic examinations were performed on the sporadic RP patient, 144 genes associated with retinal diseases were scanned with capture next generation sequencing (CNGS) approach. Two heterozygous mutations in PDE6B were confirmed in the pedigree by Sanger sequencing subsequently. The carrier frequency of PDE6B mutations of reported PDE6B mutations based on the available two public exome databases (1000 Genomes Project and ESP6500 Genomes Project) and one in-house exome database was investigated. RESULTS: We identified compound heterozygosity of two novel nonsense mutations c.1133G>A (p.W378X) and c.2395C>T (p.R799X) in PDE6B, one reported causative gene for RP. Neither of the two mutations in our study was presented in three exome databases. Two mutations (p.R74C and p.T604I) in PDE6B have relatively high frequencies in the ESP6500 and in-house databases, respectively, while no common dominant mutation in each of the database or across all databases. CONCLUSION: We demonstrates that compound heterozygosity of two novel nonsense mutations in PDE6B could lead to RP. These results collectively point to enormous potential of next-generation sequencing in determining the genetic etiology of RP and how various mutations in PDE6B contribute to the genetic heterogeneity of RP.

Draft Genome Sequence of Bacillus megaterium BHG1.1, a Strain Isolated from Bar-Headed Goose (Anser indicus) Feces on the Qinghai-Tibet Plateau.

Bacillus megaterium is a soil-inhabiting Gram-positive bacterium that is routinely used in industrial applications for recombinant protein production and bioremediation. Studies involving Bacillus megaterium isolated from waterfowl are scarce. Here, we report a 6.26-Mbp draft genome sequence of Bacillus megaterium BHG1.1, which was isolated from feces of a bar-headed goose.

WISP-1 contributes to fractionated irradiation-induced radioresistance in esophageal carcinoma cell lines and mice.

Cancer cells that survive fractionated irradiation can be radioresistant and cause tumor recurrence. However, the molecular mechanisms underlying the development of radioresistance in cancer cells remain elusive. The aim of this study was to investigate the role of WISP-1 in the development of radioresistance in esophageal carcinoma during fractionated irradiation. Radioresistant esophageal cancer cells were generated from normal esophageal cancer cells via fractionated irradiation, and expression levels of related proteins were determined by Western blot. Radiosensitivity of cells was established by clonogenic cell survival assays, and cell cycle distribution was evaluated by flow cytometry. Protein distributions were determined by immunofluorescence, and cell toxicity was evaluated by cell counting kit-8 assays. In vivo validations were performed in a xenograft transplantation mouse model. Our data indicate that WISP-1 plays an important role in the development of radioresistance in esophageal cancer cells during fractionated irradiation. The overexression of WISP-1 in esophageal cancer cells was associated with radioresistance. Depletion of extracellular WISP-1 by antibody neutralizing reversed radioresistance and directly induced mitotic catastrophe resulting in cell death. WISP-1 may be a candidate therapeutic target in the treatment of recurrent esophageal carcinoma after radiotherapy.