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miR-142 orchestrates a network of actin cytoskeleton regulators during megakaryopoiesis
Genome-encoded microRNAs (miRNAs) provide a posttranscriptional regulatory layer that controls the differentiation and function of various cellular systems, including hematopoietic cells. miR-142 is one of the most prevalently expressed miRNAs within the hematopoietic lineage. To address the in vivo...
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Published in: | eLife 2014-05, Vol.3, p.e01964-e01964 |
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creator | Chapnik, Elik Rivkin, Natalia Mildner, Alexander Beck, Gilad Pasvolsky, Ronit Metzl-Raz, Eyal Birger, Yehudit Amir, Gail Tirosh, Itay Porat, Ziv Israel, Liron L Lellouche, Emmanuel Michaeli, Shulamit Lellouche, Jean-Paul M Izraeli, Shai Jung, Steffen Hornstein, Eran |
description | Genome-encoded microRNAs (miRNAs) provide a posttranscriptional regulatory layer that controls the differentiation and function of various cellular systems, including hematopoietic cells. miR-142 is one of the most prevalently expressed miRNAs within the hematopoietic lineage. To address the in vivo functions of miR-142, we utilized a novel reporter and a loss-of-function mouse allele that we have recently generated. In this study, we show that miR-142 is broadly expressed in the adult hematopoietic system. Our data further reveal that miR-142 is critical for megakaryopoiesis. Genetic ablation of miR-142 caused impaired megakaryocyte maturation, inhibition of polyploidization, abnormal proplatelet formation, and thrombocytopenia. Finally, we characterized a network of miR-142-3p targets which collectively control actin filament homeostasis, thereby ensuring proper execution of actin-dependent proplatelet formation. Our study reveals a pivotal role for miR-142 activity in megakaryocyte maturation and function, and demonstrates a critical contribution of a single miRNA in orchestrating cytoskeletal dynamics and normal hemostasis.DOI: http://dx.doi.org/10.7554/eLife.01964.001. |
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To address the in vivo functions of miR-142, we utilized a novel reporter and a loss-of-function mouse allele that we have recently generated. In this study, we show that miR-142 is broadly expressed in the adult hematopoietic system. Our data further reveal that miR-142 is critical for megakaryopoiesis. Genetic ablation of miR-142 caused impaired megakaryocyte maturation, inhibition of polyploidization, abnormal proplatelet formation, and thrombocytopenia. Finally, we characterized a network of miR-142-3p targets which collectively control actin filament homeostasis, thereby ensuring proper execution of actin-dependent proplatelet formation. Our study reveals a pivotal role for miR-142 activity in megakaryocyte maturation and function, and demonstrates a critical contribution of a single miRNA in orchestrating cytoskeletal dynamics and normal hemostasis.DOI: http://dx.doi.org/10.7554/eLife.01964.001.</description><identifier>ISSN: 2050-084X</identifier><identifier>EISSN: 2050-084X</identifier><identifier>DOI: 10.7554/elife.01964</identifier><identifier>PMID: 24859754</identifier><language>eng</language><publisher>England: eLife Sciences Publications Ltd</publisher><subject>Ablation ; Actin ; Actin Cytoskeleton - metabolism ; Animals ; Biosynthesis ; Blood ; Blood platelets ; Cell Biology ; Cytoskeletal Proteins - genetics ; Cytoskeletal Proteins - metabolism ; Cytoskeleton ; Developmental Biology and Stem Cells ; Experiments ; Gene expression ; Gene Expression Regulation ; Genomes ; Genotype ; HEK293 Cells ; Hemostasis ; Homeostasis ; Humans ; Laboratories ; Medical research ; megakaryocytes ; Megakaryocytes - metabolism ; Megakaryocytes - pathology ; megakaryopoiesis ; Mice, Inbred C57BL ; Mice, Knockout ; microRNA ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miR-142 ; miRNA ; Phenotype ; Polyploidy ; Post-transcription ; Proteins ; RNA Interference ; Signal Transduction ; Thrombocytopenia ; Thrombocytopenia - blood ; Thrombocytopenia - genetics ; Thrombocytopenia - metabolism ; Thrombopoiesis - genetics ; Transfection</subject><ispartof>eLife, 2014-05, Vol.3, p.e01964-e01964</ispartof><rights>Copyright © 2014, Chapnik et al.</rights><rights>Copyright © 2014, Chapnik et al. This work is licensed under the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/3.0/ ) (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Copyright © 2014, Chapnik et al 2014 Chapnik et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c541t-5338a02d875890e22b6a2ebc22f233bc27c04a95583010eba54e5d2fe6a026523</citedby><cites>FETCH-LOGICAL-c541t-5338a02d875890e22b6a2ebc22f233bc27c04a95583010eba54e5d2fe6a026523</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1966563623/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1966563623?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24859754$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chapnik, Elik</creatorcontrib><creatorcontrib>Rivkin, Natalia</creatorcontrib><creatorcontrib>Mildner, Alexander</creatorcontrib><creatorcontrib>Beck, Gilad</creatorcontrib><creatorcontrib>Pasvolsky, Ronit</creatorcontrib><creatorcontrib>Metzl-Raz, Eyal</creatorcontrib><creatorcontrib>Birger, Yehudit</creatorcontrib><creatorcontrib>Amir, Gail</creatorcontrib><creatorcontrib>Tirosh, Itay</creatorcontrib><creatorcontrib>Porat, Ziv</creatorcontrib><creatorcontrib>Israel, Liron L</creatorcontrib><creatorcontrib>Lellouche, Emmanuel</creatorcontrib><creatorcontrib>Michaeli, Shulamit</creatorcontrib><creatorcontrib>Lellouche, Jean-Paul M</creatorcontrib><creatorcontrib>Izraeli, Shai</creatorcontrib><creatorcontrib>Jung, Steffen</creatorcontrib><creatorcontrib>Hornstein, Eran</creatorcontrib><title>miR-142 orchestrates a network of actin cytoskeleton regulators during megakaryopoiesis</title><title>eLife</title><addtitle>Elife</addtitle><description>Genome-encoded microRNAs (miRNAs) provide a posttranscriptional regulatory layer that controls the differentiation and function of various cellular systems, including hematopoietic cells. miR-142 is one of the most prevalently expressed miRNAs within the hematopoietic lineage. To address the in vivo functions of miR-142, we utilized a novel reporter and a loss-of-function mouse allele that we have recently generated. In this study, we show that miR-142 is broadly expressed in the adult hematopoietic system. Our data further reveal that miR-142 is critical for megakaryopoiesis. Genetic ablation of miR-142 caused impaired megakaryocyte maturation, inhibition of polyploidization, abnormal proplatelet formation, and thrombocytopenia. Finally, we characterized a network of miR-142-3p targets which collectively control actin filament homeostasis, thereby ensuring proper execution of actin-dependent proplatelet formation. Our study reveals a pivotal role for miR-142 activity in megakaryocyte maturation and function, and demonstrates a critical contribution of a single miRNA in orchestrating cytoskeletal dynamics and normal hemostasis.DOI: http://dx.doi.org/10.7554/eLife.01964.001.</description><subject>Ablation</subject><subject>Actin</subject><subject>Actin Cytoskeleton - metabolism</subject><subject>Animals</subject><subject>Biosynthesis</subject><subject>Blood</subject><subject>Blood platelets</subject><subject>Cell Biology</subject><subject>Cytoskeletal Proteins - genetics</subject><subject>Cytoskeletal Proteins - metabolism</subject><subject>Cytoskeleton</subject><subject>Developmental Biology and Stem Cells</subject><subject>Experiments</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Genomes</subject><subject>Genotype</subject><subject>HEK293 Cells</subject><subject>Hemostasis</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Laboratories</subject><subject>Medical research</subject><subject>megakaryocytes</subject><subject>Megakaryocytes - metabolism</subject><subject>Megakaryocytes - pathology</subject><subject>megakaryopoiesis</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>microRNA</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>miR-142</subject><subject>miRNA</subject><subject>Phenotype</subject><subject>Polyploidy</subject><subject>Post-transcription</subject><subject>Proteins</subject><subject>RNA Interference</subject><subject>Signal Transduction</subject><subject>Thrombocytopenia</subject><subject>Thrombocytopenia - blood</subject><subject>Thrombocytopenia - genetics</subject><subject>Thrombocytopenia - metabolism</subject><subject>Thrombopoiesis - genetics</subject><subject>Transfection</subject><issn>2050-084X</issn><issn>2050-084X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdkc1rFTEUxYMotjy7ci8BN4JMzedMshGk-FF4IIiiu5DJ3Ezz3szkmWSU_vfGvlpas7khOffH4RyEnlNy3kkp3sAUPJwTqlvxCJ0yIklDlPjx-N79BJ3lvCP1dEIpqp-iEyaU1J0Up-j7HL40VDAck7uCXJItkLHFC5TfMe1x9Ni6EhbsrkvMe5igxAUnGNfJlpgyHtYUlhHPMNq9TdfxEAPkkJ-hJ95OGc5u5wZ9-_D-68WnZvv54-XFu23jpKClkZwrS9igOqk0Acb61jLoHWOecV5n54iwWkrFCSXQWylADsxDW7dayfgGXR65Q7Q7c0hhriZMtMHcPMQ0GptKcBOYvq_rdNDaOyW8o1YT54H2mlOnvIPKentkHdZ-hsHBUuOYHkAf_izhyozxlxGk7TpJK-DVLSDFn2tN08whO5gmu0Bcs6FSkI6SlrdV-vI_6S6uaalRmdplK6umBrBBr48ql2LOCfydGUrM3_4NbGv_5qb_qn5x3_-d9l_b_A_YZ61I</recordid><startdate>20140523</startdate><enddate>20140523</enddate><creator>Chapnik, Elik</creator><creator>Rivkin, Natalia</creator><creator>Mildner, Alexander</creator><creator>Beck, Gilad</creator><creator>Pasvolsky, Ronit</creator><creator>Metzl-Raz, Eyal</creator><creator>Birger, Yehudit</creator><creator>Amir, Gail</creator><creator>Tirosh, Itay</creator><creator>Porat, Ziv</creator><creator>Israel, Liron L</creator><creator>Lellouche, Emmanuel</creator><creator>Michaeli, Shulamit</creator><creator>Lellouche, Jean-Paul M</creator><creator>Izraeli, Shai</creator><creator>Jung, Steffen</creator><creator>Hornstein, Eran</creator><general>eLife Sciences Publications Ltd</general><general>eLife Sciences Publications, Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140523</creationdate><title>miR-142 orchestrates a network of actin cytoskeleton regulators during megakaryopoiesis</title><author>Chapnik, Elik ; Rivkin, Natalia ; Mildner, Alexander ; Beck, Gilad ; Pasvolsky, Ronit ; Metzl-Raz, Eyal ; Birger, Yehudit ; Amir, Gail ; Tirosh, Itay ; Porat, Ziv ; Israel, Liron L ; Lellouche, Emmanuel ; Michaeli, Shulamit ; Lellouche, Jean-Paul M ; Izraeli, Shai ; Jung, Steffen ; Hornstein, Eran</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c541t-5338a02d875890e22b6a2ebc22f233bc27c04a95583010eba54e5d2fe6a026523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Ablation</topic><topic>Actin</topic><topic>Actin Cytoskeleton - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>eLife</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chapnik, Elik</au><au>Rivkin, Natalia</au><au>Mildner, Alexander</au><au>Beck, Gilad</au><au>Pasvolsky, Ronit</au><au>Metzl-Raz, Eyal</au><au>Birger, Yehudit</au><au>Amir, Gail</au><au>Tirosh, Itay</au><au>Porat, Ziv</au><au>Israel, Liron L</au><au>Lellouche, Emmanuel</au><au>Michaeli, Shulamit</au><au>Lellouche, Jean-Paul M</au><au>Izraeli, Shai</au><au>Jung, Steffen</au><au>Hornstein, Eran</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-142 orchestrates a network of actin cytoskeleton regulators during megakaryopoiesis</atitle><jtitle>eLife</jtitle><addtitle>Elife</addtitle><date>2014-05-23</date><risdate>2014</risdate><volume>3</volume><spage>e01964</spage><epage>e01964</epage><pages>e01964-e01964</pages><issn>2050-084X</issn><eissn>2050-084X</eissn><abstract>Genome-encoded microRNAs (miRNAs) provide a posttranscriptional regulatory layer that controls the differentiation and function of various cellular systems, including hematopoietic cells. miR-142 is one of the most prevalently expressed miRNAs within the hematopoietic lineage. To address the in vivo functions of miR-142, we utilized a novel reporter and a loss-of-function mouse allele that we have recently generated. In this study, we show that miR-142 is broadly expressed in the adult hematopoietic system. Our data further reveal that miR-142 is critical for megakaryopoiesis. Genetic ablation of miR-142 caused impaired megakaryocyte maturation, inhibition of polyploidization, abnormal proplatelet formation, and thrombocytopenia. Finally, we characterized a network of miR-142-3p targets which collectively control actin filament homeostasis, thereby ensuring proper execution of actin-dependent proplatelet formation. Our study reveals a pivotal role for miR-142 activity in megakaryocyte maturation and function, and demonstrates a critical contribution of a single miRNA in orchestrating cytoskeletal dynamics and normal hemostasis.DOI: http://dx.doi.org/10.7554/eLife.01964.001.</abstract><cop>England</cop><pub>eLife Sciences Publications Ltd</pub><pmid>24859754</pmid><doi>10.7554/elife.01964</doi><oa>free_for_read</oa></addata></record> |
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subjects | Ablation Actin Actin Cytoskeleton - metabolism Animals Biosynthesis Blood Blood platelets Cell Biology Cytoskeletal Proteins - genetics Cytoskeletal Proteins - metabolism Cytoskeleton Developmental Biology and Stem Cells Experiments Gene expression Gene Expression Regulation Genomes Genotype HEK293 Cells Hemostasis Homeostasis Humans Laboratories Medical research megakaryocytes Megakaryocytes - metabolism Megakaryocytes - pathology megakaryopoiesis Mice, Inbred C57BL Mice, Knockout microRNA MicroRNAs - genetics MicroRNAs - metabolism miR-142 miRNA Phenotype Polyploidy Post-transcription Proteins RNA Interference Signal Transduction Thrombocytopenia Thrombocytopenia - blood Thrombocytopenia - genetics Thrombocytopenia - metabolism Thrombopoiesis - genetics Transfection |
title | miR-142 orchestrates a network of actin cytoskeleton regulators during megakaryopoiesis |
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