CD81 is essential for the re-entry of hematopoietic stem cells to quiescence following stress-induced proliferation via deactivation of the Akt pathway
The regulatory mechanisms governing the cell cycle progression of hematopoietic stem cells (HSCs) are well characterized, but those responsible for the return of proliferating HSCs to a quiescent state remain largely unknown. Here, we present evidence that CD81, a tetraspanin molecule acutely respon...
Gespeichert in:
| Veröffentlicht in: | PLoS biology 2011-09, Vol.9 (9), p.e1001148-e1001148 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e1001148 |
|---|---|
| container_issue | 9 |
| container_start_page | e1001148 |
| container_title | PLoS biology |
| container_volume | 9 |
| creator | Lin, Kuanyin K Rossi, Lara Boles, Nathan C Hall, Brian E George, Thaddeus C Goodell, Margaret A |
| description | The regulatory mechanisms governing the cell cycle progression of hematopoietic stem cells (HSCs) are well characterized, but those responsible for the return of proliferating HSCs to a quiescent state remain largely unknown. Here, we present evidence that CD81, a tetraspanin molecule acutely responsive to proliferative stress, is essential for the maintenance of long-term repopulating HSCs. Cd81(-/-) HSCs showed a marked engraftment defect when transplanted into secondary recipient mice and a significantly delayed return to quiescence when stimulated to proliferate with 5-fluorouracil (5FU). In addition, we found that CD81 proteins form a polarized patch when HSCs are returning to quiescence. Thus, we propose that the spatial distribution of CD81 during the HSC recovery phase drives proliferative HSC to quiescence, and is important to preserve the self-renewal properties. Here, we show that lack of CD81 leads to loss of HSC self-renewal, and the clustering of CD81 on HSC membrane results in deactivation of Akt, which subsequently leads to nuclear translocation of FoxO1a. Thus, CD81 functions as part of a previously undefined mechanism that prohibits excessive proliferation of HSCs exposed to environmental stress. |
| doi_str_mv | 10.1371/journal.pbio.1001148 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1314505652</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A269029075</galeid><doaj_id>oai_doaj_org_article_f7fd64cce3fa4f97bac214d24dce9323</doaj_id><sourcerecordid>A269029075</sourcerecordid><originalsourceid>FETCH-LOGICAL-c666t-c93b741593c79db7fcb2ac750a4d2bf3bbe537cce931f2923eb5f9884d6bc01b3</originalsourceid><addsrcrecordid>eNqVk9uO0zAQhiMEYpeFN0BgiQvERUp8SJzcIFXlVGnFSpxuLdsZt17SOGs7XfokvC4O7a62EhcgX8T6880_4xlNlj3FxQxTjl9futH3spsNyroZLgqMWX0vO8UlK3Ne1-X9O_eT7FEIl0VBSEPqh9kJwQ3FJaWn2a_F2xojGxCEAH20skPGeRTXgDzkSfE75Axaw0ZGNzgL0WoUImyQhq4LKDp0NVoIGnoNKbTr3LXtVwnxyTG3fTtqaNHgXWcNeBmt69HWStSC1NFu90LKMGWc_4hokHF9LXePswdGdgGeHL5n2bf3774uPubnFx-Wi_l5rquqirluqOIMlw3VvGkVN1oRqXlZSNYSZahSUFKuNaT3mvR4Cqo0TV2ztlK6wIqeZc_3vkPngjj0NAhMMSuLsipJIpZ7onXyUgzebqTfCSet-CM4vxLSp650IAw3bcVSNmokMw1XUhOcCmHtVAChyevNIduoNpDU1F_ZHZke_-ntWqzcVlDMp5klg5cHA--uRghRbGyYJiF7cGMQdUrDGWlYIl_syZVMldneuGSoJ1rMSdUUpCl4majZX6h0WthY7XowNulHAa-OAhIT4WdcyTEEsfzy-T_YT__OXnw_Ztme1d6F4MHcNhAXYtqNmzmKaTfEYTdS2LO7zb8NulkG-hupJg4I</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>893274294</pqid></control><display><type>article</type><title>CD81 is essential for the re-entry of hematopoietic stem cells to quiescence following stress-induced proliferation via deactivation of the Akt pathway</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Lin, Kuanyin K ; Rossi, Lara ; Boles, Nathan C ; Hall, Brian E ; George, Thaddeus C ; Goodell, Margaret A</creator><contributor>Eaves, Connie J.</contributor><creatorcontrib>Lin, Kuanyin K ; Rossi, Lara ; Boles, Nathan C ; Hall, Brian E ; George, Thaddeus C ; Goodell, Margaret A ; Eaves, Connie J.</creatorcontrib><description>The regulatory mechanisms governing the cell cycle progression of hematopoietic stem cells (HSCs) are well characterized, but those responsible for the return of proliferating HSCs to a quiescent state remain largely unknown. Here, we present evidence that CD81, a tetraspanin molecule acutely responsive to proliferative stress, is essential for the maintenance of long-term repopulating HSCs. Cd81(-/-) HSCs showed a marked engraftment defect when transplanted into secondary recipient mice and a significantly delayed return to quiescence when stimulated to proliferate with 5-fluorouracil (5FU). In addition, we found that CD81 proteins form a polarized patch when HSCs are returning to quiescence. Thus, we propose that the spatial distribution of CD81 during the HSC recovery phase drives proliferative HSC to quiescence, and is important to preserve the self-renewal properties. Here, we show that lack of CD81 leads to loss of HSC self-renewal, and the clustering of CD81 on HSC membrane results in deactivation of Akt, which subsequently leads to nuclear translocation of FoxO1a. Thus, CD81 functions as part of a previously undefined mechanism that prohibits excessive proliferation of HSCs exposed to environmental stress.</description><identifier>ISSN: 1545-7885</identifier><identifier>ISSN: 1544-9173</identifier><identifier>EISSN: 1545-7885</identifier><identifier>DOI: 10.1371/journal.pbio.1001148</identifier><identifier>PMID: 21931533</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Biology ; Bone marrow ; Cell cycle ; Cell Proliferation ; Enzyme Activation ; Flow Cytometry ; Forkhead Box Protein O1 ; Forkhead Transcription Factors - genetics ; Forkhead Transcription Factors - metabolism ; Gene Expression Regulation ; Hematopoietic Stem Cell Transplantation - methods ; Hematopoietic stem cells ; Hematopoietic Stem Cells - cytology ; Hematopoietic Stem Cells - drug effects ; Hematopoietic Stem Cells - metabolism ; MAP Kinase Signaling System ; Mice ; Mice, Inbred C57BL ; Mitogen-Activated Protein Kinases - antagonists & inhibitors ; Mitogen-Activated Protein Kinases - genetics ; Mitogen-Activated Protein Kinases - metabolism ; Oxidative Stress ; Phosphorylcholine - analogs & derivatives ; Phosphorylcholine - pharmacology ; Physiological aspects ; Protein kinases ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; Stem cells ; Tetraspanin 28 - genetics ; Tetraspanin 28 - metabolism ; Transplantation Conditioning</subject><ispartof>PLoS biology, 2011-09, Vol.9 (9), p.e1001148-e1001148</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>Lin et al. 2011</rights><rights>2011 Lin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Lin KK, Rossi L, Boles NC, Hall BE, George TC, et al. (2011) CD81 Is Essential for the Re-entry of Hematopoietic Stem Cells to Quiescence following Stress-Induced Proliferation Via Deactivation of the Akt Pathway. PLoS Biol 9(9): e1001148. doi:10.1371/journal.pbio.1001148</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c666t-c93b741593c79db7fcb2ac750a4d2bf3bbe537cce931f2923eb5f9884d6bc01b3</citedby><cites>FETCH-LOGICAL-c666t-c93b741593c79db7fcb2ac750a4d2bf3bbe537cce931f2923eb5f9884d6bc01b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172193/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172193/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21931533$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Eaves, Connie J.</contributor><creatorcontrib>Lin, Kuanyin K</creatorcontrib><creatorcontrib>Rossi, Lara</creatorcontrib><creatorcontrib>Boles, Nathan C</creatorcontrib><creatorcontrib>Hall, Brian E</creatorcontrib><creatorcontrib>George, Thaddeus C</creatorcontrib><creatorcontrib>Goodell, Margaret A</creatorcontrib><title>CD81 is essential for the re-entry of hematopoietic stem cells to quiescence following stress-induced proliferation via deactivation of the Akt pathway</title><title>PLoS biology</title><addtitle>PLoS Biol</addtitle><description>The regulatory mechanisms governing the cell cycle progression of hematopoietic stem cells (HSCs) are well characterized, but those responsible for the return of proliferating HSCs to a quiescent state remain largely unknown. Here, we present evidence that CD81, a tetraspanin molecule acutely responsive to proliferative stress, is essential for the maintenance of long-term repopulating HSCs. Cd81(-/-) HSCs showed a marked engraftment defect when transplanted into secondary recipient mice and a significantly delayed return to quiescence when stimulated to proliferate with 5-fluorouracil (5FU). In addition, we found that CD81 proteins form a polarized patch when HSCs are returning to quiescence. Thus, we propose that the spatial distribution of CD81 during the HSC recovery phase drives proliferative HSC to quiescence, and is important to preserve the self-renewal properties. Here, we show that lack of CD81 leads to loss of HSC self-renewal, and the clustering of CD81 on HSC membrane results in deactivation of Akt, which subsequently leads to nuclear translocation of FoxO1a. Thus, CD81 functions as part of a previously undefined mechanism that prohibits excessive proliferation of HSCs exposed to environmental stress.</description><subject>Animals</subject><subject>Biology</subject><subject>Bone marrow</subject><subject>Cell cycle</subject><subject>Cell Proliferation</subject><subject>Enzyme Activation</subject><subject>Flow Cytometry</subject><subject>Forkhead Box Protein O1</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Hematopoietic Stem Cell Transplantation - methods</subject><subject>Hematopoietic stem cells</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - drug effects</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>MAP Kinase Signaling System</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>Mitogen-Activated Protein Kinases - genetics</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Oxidative Stress</subject><subject>Phosphorylcholine - analogs & derivatives</subject><subject>Phosphorylcholine - pharmacology</subject><subject>Physiological aspects</subject><subject>Protein kinases</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Stem cells</subject><subject>Tetraspanin 28 - genetics</subject><subject>Tetraspanin 28 - metabolism</subject><subject>Transplantation Conditioning</subject><issn>1545-7885</issn><issn>1544-9173</issn><issn>1545-7885</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqVk9uO0zAQhiMEYpeFN0BgiQvERUp8SJzcIFXlVGnFSpxuLdsZt17SOGs7XfokvC4O7a62EhcgX8T6880_4xlNlj3FxQxTjl9futH3spsNyroZLgqMWX0vO8UlK3Ne1-X9O_eT7FEIl0VBSEPqh9kJwQ3FJaWn2a_F2xojGxCEAH20skPGeRTXgDzkSfE75Axaw0ZGNzgL0WoUImyQhq4LKDp0NVoIGnoNKbTr3LXtVwnxyTG3fTtqaNHgXWcNeBmt69HWStSC1NFu90LKMGWc_4hokHF9LXePswdGdgGeHL5n2bf3774uPubnFx-Wi_l5rquqirluqOIMlw3VvGkVN1oRqXlZSNYSZahSUFKuNaT3mvR4Cqo0TV2ztlK6wIqeZc_3vkPngjj0NAhMMSuLsipJIpZ7onXyUgzebqTfCSet-CM4vxLSp650IAw3bcVSNmokMw1XUhOcCmHtVAChyevNIduoNpDU1F_ZHZke_-ntWqzcVlDMp5klg5cHA--uRghRbGyYJiF7cGMQdUrDGWlYIl_syZVMldneuGSoJ1rMSdUUpCl4majZX6h0WthY7XowNulHAa-OAhIT4WdcyTEEsfzy-T_YT__OXnw_Ztme1d6F4MHcNhAXYtqNmzmKaTfEYTdS2LO7zb8NulkG-hupJg4I</recordid><startdate>20110901</startdate><enddate>20110901</enddate><creator>Lin, Kuanyin K</creator><creator>Rossi, Lara</creator><creator>Boles, Nathan C</creator><creator>Hall, Brian E</creator><creator>George, Thaddeus C</creator><creator>Goodell, Margaret A</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><scope>CZG</scope></search><sort><creationdate>20110901</creationdate><title>CD81 is essential for the re-entry of hematopoietic stem cells to quiescence following stress-induced proliferation via deactivation of the Akt pathway</title><author>Lin, Kuanyin K ; Rossi, Lara ; Boles, Nathan C ; Hall, Brian E ; George, Thaddeus C ; Goodell, Margaret A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c666t-c93b741593c79db7fcb2ac750a4d2bf3bbe537cce931f2923eb5f9884d6bc01b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Biology</topic><topic>Bone marrow</topic><topic>Cell cycle</topic><topic>Cell Proliferation</topic><topic>Enzyme Activation</topic><topic>Flow Cytometry</topic><topic>Forkhead Box Protein O1</topic><topic>Forkhead Transcription Factors - genetics</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Hematopoietic Stem Cell Transplantation - methods</topic><topic>Hematopoietic stem cells</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hematopoietic Stem Cells - drug effects</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>MAP Kinase Signaling System</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mitogen-Activated Protein Kinases - antagonists & inhibitors</topic><topic>Mitogen-Activated Protein Kinases - genetics</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Oxidative Stress</topic><topic>Phosphorylcholine - analogs & derivatives</topic><topic>Phosphorylcholine - pharmacology</topic><topic>Physiological aspects</topic><topic>Protein kinases</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Stem cells</topic><topic>Tetraspanin 28 - genetics</topic><topic>Tetraspanin 28 - metabolism</topic><topic>Transplantation Conditioning</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lin, Kuanyin K</creatorcontrib><creatorcontrib>Rossi, Lara</creatorcontrib><creatorcontrib>Boles, Nathan C</creatorcontrib><creatorcontrib>Hall, Brian E</creatorcontrib><creatorcontrib>George, Thaddeus C</creatorcontrib><creatorcontrib>Goodell, Margaret A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><collection>PLoS Biology</collection><jtitle>PLoS biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, Kuanyin K</au><au>Rossi, Lara</au><au>Boles, Nathan C</au><au>Hall, Brian E</au><au>George, Thaddeus C</au><au>Goodell, Margaret A</au><au>Eaves, Connie J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CD81 is essential for the re-entry of hematopoietic stem cells to quiescence following stress-induced proliferation via deactivation of the Akt pathway</atitle><jtitle>PLoS biology</jtitle><addtitle>PLoS Biol</addtitle><date>2011-09-01</date><risdate>2011</risdate><volume>9</volume><issue>9</issue><spage>e1001148</spage><epage>e1001148</epage><pages>e1001148-e1001148</pages><issn>1545-7885</issn><issn>1544-9173</issn><eissn>1545-7885</eissn><abstract>The regulatory mechanisms governing the cell cycle progression of hematopoietic stem cells (HSCs) are well characterized, but those responsible for the return of proliferating HSCs to a quiescent state remain largely unknown. Here, we present evidence that CD81, a tetraspanin molecule acutely responsive to proliferative stress, is essential for the maintenance of long-term repopulating HSCs. Cd81(-/-) HSCs showed a marked engraftment defect when transplanted into secondary recipient mice and a significantly delayed return to quiescence when stimulated to proliferate with 5-fluorouracil (5FU). In addition, we found that CD81 proteins form a polarized patch when HSCs are returning to quiescence. Thus, we propose that the spatial distribution of CD81 during the HSC recovery phase drives proliferative HSC to quiescence, and is important to preserve the self-renewal properties. Here, we show that lack of CD81 leads to loss of HSC self-renewal, and the clustering of CD81 on HSC membrane results in deactivation of Akt, which subsequently leads to nuclear translocation of FoxO1a. Thus, CD81 functions as part of a previously undefined mechanism that prohibits excessive proliferation of HSCs exposed to environmental stress.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21931533</pmid><doi>10.1371/journal.pbio.1001148</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1545-7885 |
| ispartof | PLoS biology, 2011-09, Vol.9 (9), p.e1001148-e1001148 |
| issn | 1545-7885 1544-9173 1545-7885 |
| language | eng |
| recordid | cdi_plos_journals_1314505652 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Animals Biology Bone marrow Cell cycle Cell Proliferation Enzyme Activation Flow Cytometry Forkhead Box Protein O1 Forkhead Transcription Factors - genetics Forkhead Transcription Factors - metabolism Gene Expression Regulation Hematopoietic Stem Cell Transplantation - methods Hematopoietic stem cells Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - drug effects Hematopoietic Stem Cells - metabolism MAP Kinase Signaling System Mice Mice, Inbred C57BL Mitogen-Activated Protein Kinases - antagonists & inhibitors Mitogen-Activated Protein Kinases - genetics Mitogen-Activated Protein Kinases - metabolism Oxidative Stress Phosphorylcholine - analogs & derivatives Phosphorylcholine - pharmacology Physiological aspects Protein kinases Proteins Proto-Oncogene Proteins c-akt - metabolism Stem cells Tetraspanin 28 - genetics Tetraspanin 28 - metabolism Transplantation Conditioning |
| title | CD81 is essential for the re-entry of hematopoietic stem cells to quiescence following stress-induced proliferation via deactivation of the Akt pathway |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T14%3A58%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=CD81%20is%20essential%20for%20the%20re-entry%20of%20hematopoietic%20stem%20cells%20to%20quiescence%20following%20stress-induced%20proliferation%20via%20deactivation%20of%20the%20Akt%20pathway&rft.jtitle=PLoS%20biology&rft.au=Lin,%20Kuanyin%20K&rft.date=2011-09-01&rft.volume=9&rft.issue=9&rft.spage=e1001148&rft.epage=e1001148&rft.pages=e1001148-e1001148&rft.issn=1545-7885&rft.eissn=1545-7885&rft_id=info:doi/10.1371/journal.pbio.1001148&rft_dat=%3Cgale_plos_%3EA269029075%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=893274294&rft_id=info:pmid/21931533&rft_galeid=A269029075&rft_doaj_id=oai_doaj_org_article_f7fd64cce3fa4f97bac214d24dce9323&rfr_iscdi=true |