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Abnormal chromatin remodeling caused by ARID1A deletion leads to malformation of the dentate gyrus

Cell Death & Differentiation volume 30, pages 2187–2199 (2023)Cite this article

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Abstract

ARID1A, an SWI/SNF chromatin-remodeling gene, is commonly mutated in cancer and hypothesized to be a tumor suppressor. Recently, loss-of-function of ARID1A gene has been shown to cause intellectual disability. Here we generate Arid1a conditional knockout mice and investigate Arid1a function in the hippocampus. Disruption of Arid1a in mouse forebrain significantly decreases neural stem/progenitor cells (NSPCs) proliferation and differentiation to neurons within the dentate gyrus (DG), increasing perinatal and postnatal apoptosis, leading to reduced hippocampus size. Moreover, we perform single-cell RNA sequencing (scRNA-seq) to investigate cellular heterogeneity and reveal that Arid1a is necessary for the maintenance of the DG progenitor pool and survival of post-mitotic neurons. Transcriptome and ChIP-seq analysis data demonstrate that ARID1A specifically regulates Prox1 by altering the levels of histone modifications. Overexpression of downstream target Prox1 can rescue proliferation and differentiation defects of NSPCs caused by Arid1a deletion. Overall, our results demonstrate a critical role for Arid1a in the development of the hippocampus and may also provide insight into the genetic basis of intellectual disabilities such as Coffin–Siris syndrome, which is caused by germ-line mutations or microduplication of Arid1a.

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Fig. 1: Lack of Arid1a shows disorganized dentate gyrus development.
Fig. 2: Transcriptional profiles of Arid1a cKO mice hippocampi associated compositional changes of neuronal cells at single-cell level.
Fig. 3: Trajectory analysis using Monocle 2 reveals Arid1a is required for neural differentiation in DG at single-cell level.
Fig. 4: Reduced proliferation and differentiation of hippocampal NSPCs of Arid1a cKO mice in vivo.
Fig. 5: Deletion of Arid1a disrupts proliferation and differentiation of hippocampal NSPCs in vitro.
Fig. 6: Loss of Arid1a results in profiling changes in histone modifications and abnormal gene transcriptions.
Fig. 7: Overexpression of Prox1 rescue impaired NSPCs proliferation and differentiation caused by Arid1a deletion in hippocampus.

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Data availability

The scRNA-seq data used in this study have been deposited in the Genome Sequence Archive in the National Genomics Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences with accession number GSA: CRA010586. The ChIP-seq data used in this study have been deposited in the Gene Expression Omnibus (GEO) under accession number GSE169562.

References

  1. Bartsocas CS, Tsiantos AK. Mental retardation with absent fifth fingernail and terminal phalanx. Am J Dis Child. 1970;120:493–4.

    CAS  PubMed  Google Scholar 

  2. Tsurusaki Y, Okamoto N, Ohashi H, Kosho T, Imai Y, Hibi-Ko Y, et al. Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. Nat Genet. 2012;44:376–8.

    Article  CAS  PubMed  Google Scholar 

  3. Wilson BG, Roberts CW. SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer. 2011;11:481–92.

    Article  CAS  PubMed  Google Scholar 

  4. Clapier CR, Cairns BR. The biology of chromatin remodeling complexes. Annu Rev Biochem. 2009;78:273–304.

    Article  CAS  PubMed  Google Scholar 

  5. Bultman S, Gebuhr T, Yee D, La Mantia C, Nicholson J, Gilliam A, et al. A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes. Mol Cell. 2000;6:1287–95.

    Article  CAS  PubMed  Google Scholar 

  6. Diana CH, Gerald RC. ATP-dependent chromatin remodeling: genetics, genomics and mechanisms. Cell Res. 2011;21:396–420.

    Article  Google Scholar 

  7. Chandler RL, Brennan J, Schisler JC, Serber D, Patterson C, Magnuson T. ARID1a-DNA interactions are required for promoter occupancy by SWI/SNF. Mol Cell Biol. 2013;33:265–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kadoch C, Hargreaves DC, Hodges C, Elias L, Ho L, Ranish J, et al. Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat Genet. 2013;45:592–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Takeda T, Banno K, Okawa R, Yanokura M, Iijima M, Irie-Kunitomi H, et al. ARID1A gene mutation in ovarian and endometrial cancers (Review). Oncol Rep. 2016;35:607–13.

    Article  CAS  PubMed  Google Scholar 

  10. Zang ZJ, Cutcutache I, Poon SL, Zhang SL, McPherson JR, Tao J, et al. Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes. Nat Genet. 2012;44:570–4.

    Article  CAS  PubMed  Google Scholar 

  11. Wu JN, Roberts CWM. ARID1A mutations in cancer: another epigenetic tumor suppressor? Cancer Discov. 2013;3:35–43.

    Article  CAS  PubMed  Google Scholar 

  12. Ogiwara H, Takahashi K, Sasaki M, Kuroda T, Yoshida H, Watanabe R, et al. Targeting the vulnerability of glutathione metabolism in ARID1A-deficient cancers. Cancer Cell. 2019;35:177–190.e178.

    Article  CAS  PubMed  Google Scholar 

  13. Mathur R, Alver BH, San Roman AK, Wilson BG, Wang X, Agoston AT, et al. ARID1A loss impairs enhancer-mediated gene regulation and drives colon cancer in mice. Nat Genet. 2017;49:296–302.

    Article  CAS  PubMed  Google Scholar 

  14. Nagarajan S, Rao SV, Sutton J, Cheeseman D, Dunn S, Papachristou EK, et al. ARID1A influences HDAC1/BRD4 activity, intrinsic proliferative capacity and breast cancer treatment response. Nat Genet. 2020;52:187–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bidart M, El Atifi M, Miladi S, Rendu J, Satre V, Ray PF, et al. Microduplication of the ARID1A gene causes intellectual disability with recognizable syndromic features. Genet Med. 2017;19:701–10.

    Article  CAS  PubMed  Google Scholar 

  16. Gao XL, Tate P, Hu P, Tjian R, Skarnes WC, Wang ZES. cell pluripotency and germ-layer formation require the SWI/SNF chromatin remodeling component BAF250a. Proc Natl Acad Sci USA. 2008;105:6656–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Son EY, Crabtree GR. The role of BAF (mSWI/SNF) complexes in mammalian neural development. Am J Med Genet C. 2014;166:333–49.

    Article  CAS  Google Scholar 

  18. Goncalves JT, Schafer ST, Gage FH. Adult neurogenesis in the hippocampus: from stem. Cells Behav Cell. 2016;167:897–914.

    CAS  Google Scholar 

  19. Miller SM, Sahay A. Functions of adult-born neurons in hippocampal memory interference and indexing. Nat Neurosci. 2019;22:1565–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Liu C, Teng ZQ, Santistevan NJ, Szulwach KE, Guo W, Jin P, et al. Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation. Cell Stem Cell. 2010;6:433–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Liu PP, Tang GB, Xu YJ, Zeng YQ, Zhang SF, Du HZ, et al. MiR-203 interplays with polycomb repressive complexes to regulate the proliferation of neural stem/progenitor cells. Stem Cell Rep. 2017;9:190–202.

    Article  CAS  Google Scholar 

  22. Lei X, Jiao J. UTX affects neural stem cell proliferation and differentiation through PTEN signaling. Stem Cell Rep. 2018;10:1193–207.

    Article  CAS  Google Scholar 

  23. Liu X, Dai SK, Liu PP, Liu CM. Arid1a regulates neural stem/progenitor cell proliferation and differentiation during cortical development. Cell Prolif. 2021;54:e13124.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Han L, Madan V, Mayakonda A, Dakle P, Woon TW, Shyamsunder P, et al. Chromatin remodeling mediated by ARID1A is indispensable for normal hematopoiesis in mice. Leukemia. 2019;33:2291–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Abdelrahim EA, Eltony SA. Postnatal development of the hippocampal formation in male albino rats. Egypt J Histol. 2011;34:346–64.

    Article  Google Scholar 

  26. Zhou Q, Homma KJ, Poo MM. Shrinkage of dendritic spines associated with long-term depression of hippocampal synapses. Neuron. 2004;44:749–57.

    Article  CAS  PubMed  Google Scholar 

  27. Lavado A, Lagutin OV, Chow LML, Baker SJ, Oliver G. Prox1 is required for granule cell maturation and intermediate progenitor maintenance during brain neurogenesis. PLoS Biol. 2010;8:16.

    Article  Google Scholar 

  28. Yu Z, Lin D, Zhong Y, Luo B, Liu S, Fei E, et al. Transmembrane protein 108 involves in adult neurogenesis in the hippocampal dentate gyrus. Cell Biosci. 2019;9:9.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Zhong SJ, Ding WY, Sun L, Lu YF, Dong H, Fan XY, et al. Decoding the development of the human hippocampus. Nature. 2020;577:531.

    Article  CAS  PubMed  Google Scholar 

  30. Hainmueller T, Bartos M. Dentate gyrus circuits for encoding, retrieval and discrimination of episodic memories. Nat Rev Neurosci. 2020;21:153–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Schrier SA, Bodurtha JN, Burton B, Chudley AE, Chiong MAD, D'Avanzo MG, et al. The Coffin-Siris syndrome: A proposed diagnostic approach and assessment of 15 overlapping cases. Am J Med Genet Part A. 2012;158A:1865–76.

    Article  PubMed  Google Scholar 

  32. Rakic P. A small step for the cell, a giant leap for mankind: a hypothesis of neocortical expansion during evolution. Trends Neurosci. 1995;18:383–8.

    Article  CAS  PubMed  Google Scholar 

  33. Barbelanne M, Tsang WY. Molecular and cellular basis of autosomal recessive primary microcephaly. BioMed Res Int. 2014;2014:547986.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kosho T, Miyake N, Carey JC. Coffin-Siris syndrome and related disorders involving components of the BAF (mSWI/SNF) complex: historical review and recent advances using next generation sequencing. Am J Med Genet C Semin Med Genet. 2014;166C:241–51.

    Article  PubMed  Google Scholar 

  35. Bilha SC, Teodoriu L, Velicescu C, Caba L. Pituitary hypoplasia and growth hormone deficiency in a patient with Coffin-Siris syndrome and severe short stature: case report and literature review. Arch Clin Cases. 2022;9:121–5.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Barish S, Barakat TS, Michel BC, Mashtalir N, Phillips JB, Valencia AM, et al. BICRA, a SWI/SNF complex member, is associated with BAF-disorder related phenotypes in humans and model organisms. Am J Hum Genet. 2020;107:1096–112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kim JK, Huh SO, Choi H, Lee KS, Shin D, Lee C, et al. Srg3, a mouse homolog of yeast SWI3, is essential for early embryogenesis and involved in brain development. Mol Cell Biol. 2001;21:7787–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Matsumoto S, Banine F, Struve J, Xing RB, Adams C, Liu Y, et al. Brg1 is required for murine neural stem cell maintenance and gliogenesis. Dev Biol. 2006;289:372–83.

    Article  CAS  PubMed  Google Scholar 

  39. Stergiopoulos A, Elkouris M, Politis PK. Prospero-related homeobox 1 (Prox1) at the crossroads of diverse pathways during adult neural fate specification. Front Cell Neurosci 2014;8:454.

  40. Shang XY, Shi Y, He DD, Wang L, Luo Q, Deng CH, et al. ARID1A deficiency weakens BRG1-RAD21 interaction that jeopardizes chromatin compactness and drives liver cancer cell metastasis. Cell Death Dis. 2021;12:990.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Wang Z, Chen K, Jia Y, Chuang JC, Sun X, Lin YH, et al. Dual ARID1A/ARID1B loss leads to rapid carcinogenesis and disruptive redistribution of BAF complexes. Nat Cancer. 2020;1:909–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Xu P, Xu J, Li Z, Yang Z. Expression of TRPC6 in renal cortex and hippocampus of mouse during postnatal development. PLoS ONE. 2012;7:e38503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ciric T, Cahill SP, Snyder JS. Dentate gyrus neurons that are born at the peak of development, but not before or after, die in adulthood. Brain Behav. 2019;9:e01435.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Li GN, Pleasure SJ. Morphogenesis of the dentate gyrus: What we are learning from mouse mutants. Dev Neurosci. 2005;27:93–99.

    Article  CAS  PubMed  Google Scholar 

  45. Lu M, Grove EA, Miller RJ. Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor. Proc Natl Acad Sci USA. 2002;99:7090–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bagri A, Gurney T, He XP, Zou YR, Littman DR, Tessier-Lavigne M, et al. The chemokine SDF1 regulates migration of dentate granule cells. Development. 2002;129:4249–60.

    Article  CAS  PubMed  Google Scholar 

  47. Armand EJ, Li J, Xie F, Luo C, Mukamel EA. Single-cell sequencing of brain cell transcriptomes and epigenomes. Neuron. 2021;109:11–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kelso TWR, Porter DK, Amaral ML, Shokhirev MN, Benner C, Hargreaves DC. Chromatin accessibility underlies synthetic lethality of SWI/SNF subunits in ARID1A-mutant cancers. Elife. 2017;6:e30506

  49. Trizzino M, Barbieri E, Petracovici A, Wu S, Welsh SA, Owens TA, et al. The tumor suppressor ARID1A controls global transcription via pausing of RNA polymerase II. Cell Rep. 2018;23:3933–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Beique J-C, Lin D-T, Kang M-G, Aizawa H, Takamiya K, Huganir RL. Synapse-specific regulation of AMPA receptor function by PSD-95. Proc Natl Acad Sci USA. 2006;103:19535–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Liu PP, Xu YJ, Dai SK, Du HZ, Wang YY, Li XG, et al. Polycomb protein EED regulates neuronal differentiation through targeting SOX11 in hippocampal dentate gyrus. Stem Cell Rep. 2019;13:115–31.

    Article  CAS  Google Scholar 

  52. Gao J, Wang WY, Mao YW, Graff J, Guan JS, Pan L, et al. A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature. 2010;466:1105–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Liu PP, Dai SK, Mi TW, Tang GB, Wang Z, Wang H, et al. Acetate supplementation restores cognitive deficits caused by ARID1A haploinsufficiency in excitatory neurons. EMBO Mol Med. 2022;14:e15795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Doyle DZ, Lam MM, Qalieh A, Qalieh Y, Sorel A, Funk OH, et al. Chromatin remodeler Arid1a regulates subplate neuron identity and wiring of cortical connectivity. Proc Natl Acad Sci USA. 2021;118.

  55. Liu J, Liu S, Gao H, Han L, Chu X, Sheng Y, et al. Genome-wide studies reveal the essential and opposite roles of ARID1A in controlling human cardiogenesis and neurogenesis from pluripotent stem cells. Genome Biol. 2020;21:169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Bitler BG, Wu S, Park PH, Hai Y, Aird KM, Wang Y, et al. ARID1A-mutated ovarian cancers depend on HDAC6 activity. Nat Cell Biol. 2017;19:962–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Bitler BG, Aird KM, Garipov A, Li H, Amatangelo M, Kossenkov AV, et al. Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers. Nat Med. 2015;21:231–8.

    Article  CAS  PubMed  Google Scholar 

  58. Shen J, Ju Z, Zhao W, Wang L, Peng Y, Ge Z, et al. ARID1A deficiency promotes mutability and potentiates therapeutic antitumor immunity unleashed by immune checkpoint blockade. Nat Med. 2018;24:556–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Zhang M, Chen D, Xia J, Han W, Cui X, Neuenkirchen N, et al. Post-transcriptional regulation of mouse neurogenesis by Pumilio proteins. Genes Dev 2017;31:1354–69.

  60. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30:2114–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012;9:357–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The sequence alignment/map format and SAMtools. Bioinformatics. 2009;25:2078–9.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Feng JX, Liu T, Qin B, Zhang Y, Liu XS. Identifying ChIP-seq enrichment using MACS. Nat Protoc. 2012;7:1728–40.

    Article  CAS  PubMed  Google Scholar 

  64. Shao Z, Zhang Y, Yuan GC, Orkin SH, Waxman DJ. MAnorm: a robust model for quantitative comparison of ChIP-Seq data sets. Genome Biol. 2012;13:R16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Yu G, Wang LG, He QY. ChIPseeker: an R/Bioconductor package for ChIP peak annotation, comparison and visualization. Bioinformatics. 2015;31:2382–3.

    Article  CAS  PubMed  Google Scholar 

  66. Ramírez F, Ryan D, Grüning B, Bhardwaj V, Kilpert F, Richter A, et al. deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 2016;44:W160–165.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Thorvaldsdottir H, Robinson JT, Mesirov JP. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform. 2013;14:178–92.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge and thank Dr. Zhong Wang at the University of Michigan for providing Arid1aflox/flox mice.

Funding

Funding

This work was supported by grants from the National Key Research and Development Program of China Project (2021YFA1101402), the Informatization Plan of Chinese Academy of Sciences (CAS-WX2021SF-0301), and the National Science Foundation of China (82271428), and the Open Project Program of State Key Laboratory of Stem Cell and Reproductive Biology.

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  1. These authors contributed equally: Pei-Pei Liu, Shi-Ping Lu, Xiao Li.

Authors and Affiliations

  1. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China

    Pei-Pei Liu, Shi-Ping Lu, Xiao Li, Gang-Bin Tang, Xiao Liu, Shang-Kun Dai, Lin-Fei Jiao, Xi-Wen Lin, Baoyang Hu, Jianwei Jiao, Zhao-Qian Teng, Chun-Sheng Han & Chang-Mei Liu

  2. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China

    Pei-Pei Liu, Shi-Ping Lu, Xiao Li, Gang-Bin Tang, Xiao Liu, Shang-Kun Dai, Lin-Fei Jiao, Xi-Wen Lin, Baoyang Hu, Jianwei Jiao, Zhao-Qian Teng, Chun-Sheng Han & Chang-Mei Liu

  3. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China

    Pei-Pei Liu, Shi-Ping Lu, Xiao Li, Gang-Bin Tang, Xiao Liu, Shang-Kun Dai, Lin-Fei Jiao, Xi-Wen Lin, Baoyang Hu, Jianwei Jiao, Zhao-Qian Teng, Chun-Sheng Han & Chang-Mei Liu

  4. Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 100049, China

    Xiao Li, Xiao Liu, Shang-Kun Dai, Lin-Fei Jiao, Baoyang Hu, Jianwei Jiao, Zhao-Qian Teng, Chun-Sheng Han & Chang-Mei Liu

  5. Graduate Institute of Biomedical Sciences, China Medical University, No.91, Hsueh-Shih Road, Taichung, 40402, Taiwan

    Xing-Guo Li

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Contributions

P-PL: Conceptualization; formal analysis; validation; methodology; writing-original draft; approval of draft; S-PL: Data curation; methodology; validation; approval of draft. XLi: Formal analysis; methodology; validation; G-BT: Conceptualization; formal analysis, writing-original draft; XLiu: Data curation; Formal analysis; validation. S-KD: Formal analysis; validation; L-FJ: Formal analysis; validation; X-WL: Formal analysis; validation; X-GL: approval of draft; B-YH: re-analyze seq-data; approval of draft; J-WJ: re-analyze seq-data; approval of draft; Z-QT: Data curation; formal analysis and interpretation; funding acquisition; approval of draft. C-SH: Conceptualization; Project administration. C-ML: Conception and design; data curation; formal analysis and interpretation; supervision; funding acquisition; approval of draft.

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Correspondence to Zhao-Qian Teng, Chun-Sheng Han or Chang-Mei Liu.

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Liu, PP., Lu, SP., Li, X. et al. Abnormal chromatin remodeling caused by ARID1A deletion leads to malformation of the dentate gyrus. Cell Death Differ 30, 2187–2199 (2023). https://doi.org/10.1038/s41418-023-01199-w

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