A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons.

The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain1. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) heterogeneous populations in the reticular formation with broad spinal termination patterns, suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain and reticular formation for 'gain setting' of brain-spinal signals. In addition, this atlas revealed a LIM homeobox transcription factor code that parcellates the reticulospinal neurons into five molecularly distinct and spatially segregated populations. Finally, we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties. Together, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions.

Defining morphologically and genetically distinct GABAergic/cholinergic amacrine cell subtypes in the vertebrate retina.

In mammals, retinal direction selectivity originates from GABAergic/cholinergic amacrine cells (ACs) specifically expressing the sox2 gene. However, the cellular diversity of GABAergic/cholinergic ACs of other vertebrate species remains largely unexplored. Here, we identified 2 morphologically and genetically distinct GABAergic/cholinergic AC types in zebrafish, a previously undescribed bhlhe22+ type and a mammalian counterpart sox2+ type. Notably, while sole sox2 disruption removed sox2+ type, the codisruption of bhlhe22 and bhlhe23 was required to remove bhlhe22+ type. Also, both types significantly differed in dendritic arbors, lamination, and soma position. Furthermore, in vivo two-photon calcium imaging and the behavior assay suggested the direction selectivity of both AC types. Nevertheless, the 2 types showed preferential responses to moving bars of different sizes. Thus, our findings provide new cellular diversity and functional characteristics of GABAergic/cholinergic ACs in the vertebrate retina.

Her6 and Prox1a are novel regulators of photoreceptor regeneration in the zebrafish retina.

Damage to light-sensing photoreceptors (PRs) occurs in highly prevalent retinal diseases. As humans cannot regenerate new PRs, these diseases often lead to irreversible blindness. Intriguingly, animals, such as the zebrafish, can regenerate PRs efficiently and restore functional vision. Upon injury, mature Müller glia (MG) undergo reprogramming to adopt a stem cell-like state. This process is similar to cellular dedifferentiation, and results in the generation of progenitor cells, which, in turn, proliferate and differentiate to replace lost retinal neurons. In this study, we tested whether factors involved in dedifferentiation of Drosophila CNS are implicated in the regenerative response in the zebrafish retina. We found that hairy-related 6 (her6) negatively regulates of PR production by regulating the rate of cell divisions in the MG-derived progenitors. prospero homeobox 1a (prox1a) is expressed in differentiated PRs and may promote PR differentiation through phase separation. Interestingly, upon Her6 downregulation, Prox1a is precociously upregulated in the PRs, to promote PR differentiation; conversely, loss of Prox1a also induces a downregulation of Her6. Together, we identified two novel candidates of PR regeneration that cross regulate each other; these may be exploited to promote human retinal regeneration and vision recovery.

Correction: Single-cell in vivo imaging of cellular circadian oscillators in zebrafish.

[This corrects the article DOI: 10.1371/journal.pbio.3000435.].

Jag2b-Notch3/1b-mediated neuron-to-glia crosstalk controls retinal gliogenesis.

In the developing central nervous systems (CNS), neural progenitor cells generate neurons and glia in sequential order. However, the influence of neurons on glia generation remains elusive. Here, we report that photoreceptor cell-derived Jag2b is required for Notch-dependent Müller glia (MG) generation in the developing zebrafish retina. In jab2b-/- mutants, differentiating MGs are re-specified into lineage-related bipolar neuron fate at the expense of mature MG. Single-cell transcriptome analysis and knock-in animals reveal that jab2b is specifically expressed in crx+ -photoreceptor cells during MG generation. Crx promoter-driven jag2b, but not other Notch ligands, is sufficient to rescue the loss of MGs observed in jag2b-/- mutants. Furthermore, we observe a severe and moderate decrease in the number of MGs in notch3-/- and notch1b-/- mutants, respectively, and the activation of Notch3 or Notch1b rescues the MG loss in jag2b-/- mutants. Together, our findings reveal that the interaction of Jag2b and Notch3/Notch1b mediates the crosstalk between neurons and glial cells to ensure the irreversible differentiation of MG, providing novel mechanistic insights into the temporal specification of glial cell fate in a developing vertebrate CNS structure.

A systematic review and meta-analysis of acupuncture for De Quervain's tenosynovitis treatment.

BACKGROUND: De Quervain's tenosynovitis (DQt) is a prevalent chronic inflammatory musculoskeletal disorder predominantly affecting the radial aspect of the wrist. This study conducted a comprehensive review of the efficacy of acupuncture in treating De Quervain's tenosynovitis (DQt). Although there is evidence suggesting that acupuncture can alleviate symptoms of DQt-characterized by pain, swelling, and functional impairment-higher-level evidence is still required to further substantiate its efficacy and safety. This study conducted a comprehensive review of the efficacy of acupuncture in treating De Quervain's tenosynovitis (DQt). METHODS: By systematically searching databases such as PubMed, Science Direct, Web of Science, Google Scholar, EMbase, PEDro, China National Knowledge Infrastructure Database (CNKI), Wanfang Database, and Chongqing VIP China Science, Technology Journal Database (VIP), we retrieved randomized controlled trial (RCT) literature on acupuncture for DQt, with the search period extending to November 1, 2023. After extracting and assessing data from the included literature, we performed Meta-analysis using RevMan 5.4.1 software. RESULTS: The results encompassed 14 RCT papers, involving 851 patients. The Meta-analysis findings indicated that, when compared to topical analgesics, acupuncture demonstrated a significant increase in treatment effectiveness (RR = 1.24; 95% CI = 1.11, 1.39, P = 0.0002) and a notable reduction in VAS pain scores (MD = -1.06; 95% CI = -1.51, -0.61, P < 0.00001). However, no statistically significant difference was observed in conney wrist joint scores. Furthermore, acupuncture was found to reduce VAS pain scores compared to the waiting list group. In comparison to corticosteroid injections (CSI), acupuncture did not show statistical significance in VAS, effectiveness rate, and conney wrist scores. CONCLUSION: Acupuncture exhibited a promising trend in alleviating pain associated with DQt and enhancing treatment effectiveness. Nonetheless, due to limitations in the quantity and quality of the included studies, these findings warrant further validation through additional research.

Contribution of cuproptosis and Cu metabolism-associated genes to chronic obstructive pulmonary disease.

Airway epithelial cell injury plays a crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, a novel form of Cu-induced programmed cell death known as cuproptosis has not yet been thoroughly investigated in the context of COPD. Clinical reports have suggested that high copper exposure may increase the risk of COPD. In this study, we aimed to determine the expression and potential functions of cuproptosis-related genes and genes associated with copper metabolism in COPD. We initially identified 52 copper metabolism-related genes based on a review of the literature. Subsequently, we calculated the expression levels of these genes using data from four GEO datasets. To gain insights into the activated signalling pathways and underlying mechanisms in COPD patients, we conducted Gene Ontology (GO) and KEGG pathway analyses, examined protein-protein interactions, and performed weighted correlation network analysis. Our findings revealed that 18 key copper metabolism-related genes, including 5 cuproptosis-related genes, were significantly enriched in signalling pathways and biological processes associated with the development of COPD. Further analysis of clinical data and animal experiments confirmed the high expression of certain cuproptosis key regulators, such as DLD and CDKN2A, in both healthy smokers and COPD smokers. Additionally, these regulators exhibited abnormal expression in a COPD rat model. Notably, copper content was found to be elevated in the lung tissues of COPD rats, suggesting its potential involvement in cuproptosis. These findings provide an experimental foundation for further research into the role of cuproptosis in COPD. Targeting copper metabolism-related genes may represent an effective approach for the treatment of COPD.

Unifying developmental programs for embryonic and postembryonic neurogenesis in the zebrafish retina.

The zebrafish retina grows for a lifetime. Whether embryonic and postembryonic retinogenesis conform to the same developmental program is an outstanding question that remains under debate. Using single-cell RNA sequencing of ∼20,000 cells of the developing zebrafish retina at four different stages, we identified seven distinct developmental states. Each state explicitly expresses a gene set. Disruption of individual state-specific marker genes results in various defects ranging from small eyes to the loss of distinct retinal cell types. Using a similar approach, we further characterized the developmental states of postembryonic retinal stem cells (RSCs) and their progeny in the ciliary marginal zone. Expression pattern analysis of state-specific marker genes showed that the developmental states of postembryonic RSCs largely recapitulated those of their embryonic counterparts, except for some differences in rod photoreceptor genesis. Thus, our findings reveal the unifying developmental program used by the embryonic and postembryonic retinogenesis in zebrafish.

Single-cell in vivo imaging of cellular circadian oscillators in zebrafish.

The circadian clock is a cell-autonomous time-keeping mechanism established gradually during embryonic development. Here, we generated a transgenic zebrafish line carrying a destabilized fluorescent protein driven by the promoter of a core clock gene, nr1d1, to report in vivo circadian rhythm at the single-cell level. By time-lapse imaging of this fish line and 3D reconstruction, we observed the sequential initiation of the reporter expression starting at photoreceptors in the pineal gland, then spreading to the cells in other brain regions at the single-cell level. Even within the pineal gland, we found heterogeneous onset of nr1d1 expression, in which each cell undergoes circadian oscillation superimposed over a cell type-specific developmental trajectory. Furthermore, we found that single-cell expression of nr1d1 showed synchronous circadian oscillation under a light-dark (LD) cycle. Remarkably, single-cell oscillations were dramatically dampened rather than desynchronized in animals raised under constant darkness, while the developmental trend still persists. It suggests that light exposure in early zebrafish embryos has significant effect on cellular circadian oscillations.

Purinergic ATP triggers moxibustion-induced local anti-nociceptive effect on inflammatory pain model.

Purinergic signalling adenosine and its A1 receptors have been demonstrated to get involved in the mechanism of acupuncture (needling therapy) analgesia. However, whether purinergic signalling would be responsible for the local analgesic effect of moxibustion therapy, the predominant member in acupuncture family procedures also could trigger analgesic effect on pain diseases, it still remains unclear. In this study, we applied moxibustion to generate analgesic effect on complete Freund's adjuvant (CFA)-induced inflammatory pain rats and detected the purine released from moxibustioned-acupoint by high-performance liquid chromatography (HPLC) approach. Intramuscular injection of ARL67156 into the acupoint Zusanli (ST36) to inhibit the breakdown of ATP showed the analgesic effect of moxibustion was increased while intramuscular injection of ATPase to speed up ATP hydrolysis caused a reduced moxibustion-induced analgesia. These data implied that purinergic ATP at the location of ST36 acupoint is a potentially beneficial factor for moxibustion-induced analgesia.

MicroRNA: Crucial modulator in purinergic signalling involved diseases.

Both microRNAs (miRNAs) and purinergic signalling are widely and respectively expressed in various tissues of different organisms and play vital roles in a variety of physiological and pathological processes. Here, we reviewed the current publications contributed to the relationship of miRNAs and purinergic signalling in cardiovascular diseases, gastrointestinal diseases, neurological diseases, and ophthalmic diseases. We tried to decode the miRNAs-purinergic signalling network of purinergic signalling involved diseases. The evidence indicated that more than 30 miRNAs (miR-22, miR-30, miR-146, miR-150, miR-155, miR-187, etc.) directly or indirectly modulate P1 receptors (A1, A2A, A2B, A3), P2 receptors (P2X1, P2X3, P2X4, P2X7, P2Y2, P2Y6, P2Y12), and ecto-enzymes (CD39, CD73, ADA2); P2X7 and CD73 could be modulated by multiple miRNAs (P2X7: miR-21, miR-22, miR-30, miR-135a, miR-150, miR-186, miR-187, miR-216b; CD73: miR-141, miR-101, miR-193b, miR-340, miR-187, miR-30, miR-422a); miR-187 would be the common miRNA to modulate P2X7 and CD73.

PKM2 Nuclear Translocation Promotes Glial Cell Activation and Aggravates the Brain Injury of Intracerebral Hemorrhage.

BACKGROUND: The purpose of this study was to investigate the potential involvement of pyruvate kinase M2 (PKM2), an enzyme acting as a rate-limiting enzyme in the final phase of glycolysis, in the regulation of glial activation and brain damage of intracerebral hemorrhage (ICH). METHODS: Western blotting and immunofluorescence were performed to investigate PKM2 expression, terminal deoxynucleotidyl transferase deoxyurinary triphosphate (dUTP) nick end labeling staining, hematoxylin and eosin staining, and behavioral tests were employed to evaluate the brain damage of ICH mice, and RNA-seq and bioinformatic analyses were performed to detect gene expression changes in ICH mice treated with TEPP-46. RESULTS: Increased PKM2 levels in perihematomal brain tissue were found starting from 3 days following ICH and peaked at 5 and 7 days post ICH. The increased expression of PKM2 was mainly co-localized with glial fibrillary acidic protein (GFAP)+ astrocytes and ionized calcium binding adaptor molecule-1 (IBA-1)+ microglia. Furthermore, we observed a notable increase in the nuclear translocation of PKM2 in glial cells following ICH. TEPP-46 treatment significantly reduced PKM2 nuclear translocation, and effectively attenuated glial activation and brain injury, and improved functional recovery of mice with ICH. RNA-seq data indicated that 91.1% (205/225) of differentially expressed genes (DEGs) were down-regulated in the TEPP-46 treated groups compared with the vehicle-treated groups in ICH brains. Furthermore, bioinformatic analyses revealed that these down-regulated DEGs were involved in a variety of biological processes, including autophagy and metabolic processes. In addition, the majority of these downregulated DEGs had a primary high expression in neurons, with subsequent expression seen in endothelial cells, microglia, and astrocytes. CONCLUSIONS: These results indicate that increased PKM2 nuclear translocation promotes the activation of glial cells after ICH, hence aggravating ICH-induced brain damage, and aggravates the brain injury induced by ICH. This highlights a potential therapeutic target for inhibiting glial activation to attenuate brain injury after ICH.

Shared Genes of PPARG and NOS2 in Alzheimer's Disease and Ulcerative Colitis Drive Macrophages and Microglia Polarization: Evidence from Bioinformatics Analysis and Following Validation.

Emerging evidence shows that peripheral systemic inflammation, such as inflammatory bowel disease (IBD), has a close even interaction with central nervous disorders such as Alzheimer's disease (AD). This study is designed to further clarify the relationship between AD and ulcerative colitis (UC, a subclass of IBD). The GEO database was used to download gene expression profiles for AD (GSE5281) and UC (GSE47908). Bioinformatics analysis included GSEA, KEGG pathway, Gene Ontology (GO), WikiPathways, PPI network, and hub gene identification. After screening the shared genes, qRT-PCR, Western blot, and immunofluorescence were used to verify the reliability of the dataset and further confirm the shared genes. GSEA, KEGG, GO, and WikiPathways suggested that PPARG and NOS2 were identified as shared genes and hub genes by cytoHubba in AD and UC and further validated via qRT-PCR and Western blot. Our work identified PPARG and NOS2 are shared genes of AD and UC. They drive macrophages and microglia heterogeneous polarization, which may be potential targets for treating neural dysfunction induced by systemic inflammation and vice versa.

Comprehensive Analysis of PANoptosis-Related Gene Signature of Ulcerative Colitis.

Accumulating evidence shows that the abnormal increase in the mortality of intestinal epithelial cells (IECs) caused by apoptosis, pyroptosis, and necroptosis is closely related to the function of mucous membrane immunity and barrier function in patients with ulcerative colitis (UC). As a procedural death path that integrates the above-mentioned many deaths, the role of PANoptosis in UC has not been clarified. This study aims to explore the characterization of PANoptosis patterns and determine the potential biomarkers and therapeutic targets. We constructed a PANoptosis gene set and revealed significant activation of PANoptosis in UC patients based on multiple transcriptome profiles of intestinal mucosal biopsies from the GEO database. Comprehensive bioinformatics analysis revealed five key genes (ZBP1, AIM2, CASP1/8, IRF1) of PANoptosome with good diagnostic value and were highly correlated with an increase in pro-inflammatory immune cells and factors. In addition, we established a reliable ceRNA regulatory network of PANoptosis and predicted three potential small-molecule drugs sharing calcium channel blockers that were identified, among which flunarizine exhibited the highest correlation with a high binding affinity to the targets. Finally, we used the DSS-induced colitis model to validate our findings. This study identifies key genes of PANoptosis associated with UC development and hypothesizes that IRF1 as a TF promotes PANoptosome multicomponent expression, activates PANoptosis, and then induces IECs excessive death.

Deep Succinylproteomics of Brain Tissues from Intracerebral Hemorrhage with Inhibition of Toll-Like Receptor 4 Signaling.

It is unclear how Toll-like receptor (TLR) 4 signaling affects protein succinylation in the brain after intracerebral hemorrhage (ICH). Here, we constructed a mouse ICH model to investigate the changes in ICH-associated brain protein succinylation, following a treatment with a TLR4 antagonist, TAK242, using a high-resolution mass spectrometry-based, quantitative succinyllysine proteomics approach. We characterized the prevalence of approximately 6700 succinylation events and quantified approximately 3500 sites, highlighting 139 succinyllysine site changes in 40 pathways. Further analysis showed that TAK242 treatment induced an increase of 29 succinyllysine sites on 28 succinylated proteins and a reduction of 24 succinyllysine sites on 23 succinylated proteins in the ICH brains. TAK242 treatment induced both protein hypersuccinylations and hyposuccinylations, which were mainly located in the mitochondria and cytoplasm. GO analysis showed that TAK242 treatment-induced changes in the ICH-associated succinylated proteins were mostly located in synapses, membranes and vesicles, and enriched in many cellular functions/compartments, such as metabolism, synapse, and myelin. KEGG analysis showed that TAK242-induced hyposuccinylation was mainly linked to fatty acid metabolism, including elongation and degradation. Moreover, a combined analysis of the succinylproteomic data with previously published transcriptome data revealed that most of the differentially succinylated proteins induced by TAK242 treatment were mainly distributed throughout neurons, astrocytes, and endothelial cells, and the mRNAs of seven and three succinylated proteins were highly expressed in neurons and astrocytes, respectively. In conclusion, we revealed that several TLR4 signaling pathways affect the succinylation processes and pathways in mouse ICH brains, providing new insights on the ICH pathophysiological processes. Data are available via ProteomeXchange with identifier PXD025622.

Ameliorating effects of electroacupuncture on the low-grade intestinal inflammation in rat model of diarrhea-predominant irritable bowel syndrome.

BACKGROUND AND AIM: We aim to investigate the effects and mechanisms of electroacupuncture (EA) at ST25 and ST37 on the intestinal low-grade inflammation (LGI) in rat model of Diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: IBS-D model rats were established by acetic acid enema combined with restraint and tail clamping. Before EA intervention, they were divided into three groups: blank 1 group, blank 2 group, and IBS-D model group. Diarrhea symptoms and visceral pain sensitivity were evaluated. After constructed the model successfully, the remaining IBS-D model group rats were randomly divided into model group and EA group. Local intestinal inflammation (HE staining), changes of intestinal mucosa (occludin protein and microvascular diameter) were evaluated. Differences between two groups were compared using t-test or Mann-Whitney U-test. Differences among more than two groups were compared using one-way ANOVA or Kruskal-Wallis test. RESULTS: After modeling, the results of HE staining in intestinal tract of IBS-D model rats showed LGI. Compared with the model group, 4 h fecal moisture content (diarrhea index) and the AWR score were decreased in the EA group. The results of HE in EA group showed that the infiltration of intestinal inflammatory cells were alleviated. Additionally, EA significantly upregulated the expression of occludin protein and partially dilated the intestinal microvascular diameter. Pearson correlation analysis showed that the symptoms of IBS-D rats were correlated with the changes of intestinal mucosa. CONCLUSION: EA may treat intestinal LGI in IBS-D rats by upregulating the expression of occludin protein and dilating the intestinal microvascular diameter.

Transcriptome sequencing reveals core regulation modules and gene signatures of Zusanli acupoints in response to different moxibustion warm stimulation in adjuvant arthritis rat.

BACKGROUND: The efficacy of moxibustion in treating rheumatoid arthritis is recognized, but its molecular mechanism is still unclear. This study aimed to characterize the molecular map and potential key genes in the process of different moxibustion warm at Zusanli acupoint treatment of adjuvant arthritis (AA) model. METHODS: AA rat model was induced by complete Freund's adjuvant (CFA) and then accessed by foot swelling and thermal hyperalgesia test. Transcriptome sequencing, series test of cluster (STC) and weighted gene co-expression network analysis (WGCNA) were used in this study. RESULTS: CFA-induced inflammation, foot swelling, and pain in AA rats were significantly improved by moxibustion warm. Differentially expressed genes (DEGs) were screened in nine different comparison groups and a total of 4535 DEGs were identified, and these DEGs were preferentially clustered in inflammatory and immune-related pathways, such as MAPK signaling pathway. Only 1 DEG of heat shock protein 90, alpha (cytosolic), class A member 1 (Hsp90aa1) was shared in comparison groups of model with moxibustion treatment. STC analysis also revealed that Hsp90aa1 was increased in AA model, but decreased after 37 °C moxibustion intervention, and constantly decreased after 42 °C moxibustion treatment. GO and KEGG pathway analysis revealed that these genes enriched in inflammatory and immune-related pathways. Moreover, WGCNA identified that violet module was positively correlated with model temperature while negatively correlated with control, and the paleturquoise module was positively correlated with model. The violet and paleturquoise module gene were significantly enriched in MAPK signaling pathway. Importantly, Hsp90aa1 also played a central role in the violet module by interacting with multiple proteins. CONCLUSIONS: Moxibustion warm improved AA in rat, and we obtained the transcriptome profile and excavate a critical gene of Hsp90aa1, and provided insight into gene signatures for moxibustion warm at Zusanli acupoint in AA rat.

Oral administration of MnCl2 attenuated hyperlipidemia-related cardiac remodeling in ApoE-/- mice.

Manganese chloride (MnCl2) has been shown to inhibit the Yes-associated protein (YAP) in high-fat diet-fed ApoE-/- mice. Although YAP has been implicated in atherogenesis, there are limited data on the effects of MnCl2 on cardiac remodeling. In this study, we discovered, by electrocardiography, that hyperlipidemia led to spontaneous supraventricular arrhythmia (SVA) in ApoE-/- (KO) mice, with 3 of 9 KO + MnCl2 mice (33%) exhibiting lower incidence of spontaneous SVA than KO mice (6 of 10 mice, 60%). Echocardiography revealed that reduced systolic function in KO mice was reversed by MnCl2 treatment. Oil Red O staining of the aortas and biochemical analysis of lipid levels showed that MnCl2 inhibited plaque formation in a lipid metabolism-independent manner. MnCl2 inhibited inflammatory cell infiltration and reduced fibrosis, as evidenced by hematoxylin and eosin, immunohistochemical and Masson's trichrome staining, respectively. Our findings demonstrate that spontaneous SVA and reduced systolic function were blocked by MnCl2. Our findings show that MnCl2 was useful in delaying cardiac remodeling and reducing susceptibility to spontaneous SVA in a mouse model of hyperlipidemia.

Inflammation-induced mammalian target of rapamycin signaling is essential for retina regeneration.

Upon retina injury, Müller glia in the zebrafish retina respond by generating multipotent progenitors to repair the retina. However, the complete mechanisms underlying retina regeneration remain elusive. Here we report inflammation-induced mammalian target of rapamycin (mTOR) signaling in the Müller glia is essential for retina regeneration in adult zebrafish. We show after a stab injury, mTOR is rapidly activated in Müller glia and later Müller glia-derived progenitor cells (MGPCs). Importantly, mTOR is required for Müller glia dedifferentiation, as well as the proliferation of Müller glia and MGPCs. Interestingly, transient mTOR inhibition by rapamycin only reversibly suppresses MGPC proliferation, while its longer suppression by knocking down Raptor significantly inhibits the regeneration of retinal neurons. We further show mTOR promotes retina regeneration by regulating the mRNA expression of key reprogramming factors ascl1a and lin-28a, cell cycle-related genes and critical cytokines. Surprisingly, we identify microglia/macrophage-mediated inflammation as an important upstream regulator of mTOR in the Müller glia and it promotes retina regeneration through mTOR. Our study not only demonstrates the important functions of mTOR but also reveals an interesting link between inflammation and the mTOR signaling during retina regeneration.