CD24 expression identifies teratogen-sensitive fetal neural stem cell subpopulations: evidence from developmental ethanol exposure and orthotopic cell transfer models
Ethanol is a potent teratogen. Its adverse neural effects are partly mediated by disrupting fetal neurogenesis. The teratogenic process is poorly understood, and vulnerable neurogenic stages have not been identified. Identifying these is a prerequisite for therapeutic interventions to mitigate effec...
Gespeichert in:
Veröffentlicht in: | PloS one 2013-07, Vol.8 (7), p.e69560 |
---|---|
Hauptverfasser: | , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | |
---|---|
container_issue | 7 |
container_start_page | e69560 |
container_title | PloS one |
container_volume | 8 |
creator | Tingling, Joseph D Bake, Shameena Holgate, Rhonda Rawlings, Jeremy Nagsuk, Phillips P Chandrasekharan, Jayashree Schneider, Sarah L Miranda, Rajesh C |
description | Ethanol is a potent teratogen. Its adverse neural effects are partly mediated by disrupting fetal neurogenesis. The teratogenic process is poorly understood, and vulnerable neurogenic stages have not been identified. Identifying these is a prerequisite for therapeutic interventions to mitigate effects of teratogen exposures.
We used flow cytometry and qRT-PCR to screen fetal mouse-derived neurosphere cultures for ethanol-sensitive neural stem cell (NSC) subpopulations, to study NSC renewal and differentiation. The identity of vulnerable NSC populations was validated in vivo, using a maternal ethanol exposure model. Finally, the effect of ethanol exposure on the ability of vulnerable NSC subpopulations to integrate into the fetal neurogenic environment was assessed following ultrasound guided, adoptive transfer.
Ethanol decreased NSC mRNAs for c-kit, Musashi-1and GFAP. The CD24(+) NSC population, specifically the CD24(+)CD15(+) double-positive subpopulation, was selectively decreased by ethanol. Maternal ethanol exposure also resulted in decreased fetal forebrain CD24 expression. Ethanol pre-exposed CD24(+) cells exhibited increased proliferation, and deficits in cell-autonomous and cue-directed neuronal differentiation, and following orthotopic transplantation into naïve fetuses, were unable to integrate into neurogenic niches. CD24(depleted) cells retained neurosphere regeneration capacity, but following ethanol exposure, generated increased numbers of CD24(+) cells relative to controls.
Neuronal lineage committed CD24(+) cells exhibit specific vulnerability, and ethanol exposure persistently impairs this population's cell-autonomous differentiation capacity. CD24(+) cells may additionally serve as quorum sensors within neurogenic niches; their loss, leading to compensatory NSC activation, perhaps depleting renewal capacity. These data collectively advance a mechanistic hypothesis for teratogenesis leading to microencephaly. |
doi_str_mv | 10.1371/journal.pone.0069560 |
format | Article |
fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1427370344</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A478167001</galeid><doaj_id>oai_doaj_org_article_ce9e6941fcb04f51852296975e7b7862</doaj_id><sourcerecordid>A478167001</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-94e0ac0c5877c23f903a93dc700f1d0d958ea622bac64e5963dcfea88fbcc5dc3</originalsourceid><addsrcrecordid>eNqNk12L3CAUhkNp6W63_QelDRQKvZip0cTEXhSW6dfAwkK_bsWY44yL0ayaYfuH-jvr7GSXCbRQvFD0eV8Pr54se16gZUHq4u2VG70VZjk4C0uEKKsoepCdFozgBcWIPDxan2RPQrhCqCINpY-zE0waVlaInGa_Vx9wmcPN4CEE7WyuO7BRKw0hj-BFdBuwiwA26Kh3kCuIwuQWRp-mEKHPJZi0GtvBDaMRMXmEdzns9j4y8d71eQc7MG7ok3NSQdwK68z-UhdGD7mwXe583LroBi0PhtELGxT4vHcdmPA0e6SECfBsms-yH58-fl99WVxcfl6vzi8WkjIcF6wEJCSSVVPXEhPFEBGMdLJGSBUd6ljVgKAYt0LSEipG05kC0TSqlbLqJDnLXh58B-MCnyIOvChxTWpEyjIR6wPROXHFB6974X9xJzS_3XB-w4WPWhrgEhhQVhZKtqhUVdFUGDPK6grqtm4oTl7vp9vGtodOpnxSrDPT-YnVW75xO57ev2nIvphXk4F31yOE-I-SJ2ojUlXaKpfMZK-D5Odl3RQ0xVMkavkXKo0Oei3TJ1M67c8Eb2aCxES4iRsxhsDX377-P3v5c86-PmK3IEzcBmfG2681B8sDKL0LwYO6T65AfN8jd2nwfY_wqUeS7MVx6veiu6YgfwBMUhFq</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1427370344</pqid></control><display><type>article</type><title>CD24 expression identifies teratogen-sensitive fetal neural stem cell subpopulations: evidence from developmental ethanol exposure and orthotopic cell transfer models</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Tingling, Joseph D ; Bake, Shameena ; Holgate, Rhonda ; Rawlings, Jeremy ; Nagsuk, Phillips P ; Chandrasekharan, Jayashree ; Schneider, Sarah L ; Miranda, Rajesh C</creator><contributor>Mezey, Eva</contributor><creatorcontrib>Tingling, Joseph D ; Bake, Shameena ; Holgate, Rhonda ; Rawlings, Jeremy ; Nagsuk, Phillips P ; Chandrasekharan, Jayashree ; Schneider, Sarah L ; Miranda, Rajesh C ; Mezey, Eva</creatorcontrib><description>Ethanol is a potent teratogen. Its adverse neural effects are partly mediated by disrupting fetal neurogenesis. The teratogenic process is poorly understood, and vulnerable neurogenic stages have not been identified. Identifying these is a prerequisite for therapeutic interventions to mitigate effects of teratogen exposures.
We used flow cytometry and qRT-PCR to screen fetal mouse-derived neurosphere cultures for ethanol-sensitive neural stem cell (NSC) subpopulations, to study NSC renewal and differentiation. The identity of vulnerable NSC populations was validated in vivo, using a maternal ethanol exposure model. Finally, the effect of ethanol exposure on the ability of vulnerable NSC subpopulations to integrate into the fetal neurogenic environment was assessed following ultrasound guided, adoptive transfer.
Ethanol decreased NSC mRNAs for c-kit, Musashi-1and GFAP. The CD24(+) NSC population, specifically the CD24(+)CD15(+) double-positive subpopulation, was selectively decreased by ethanol. Maternal ethanol exposure also resulted in decreased fetal forebrain CD24 expression. Ethanol pre-exposed CD24(+) cells exhibited increased proliferation, and deficits in cell-autonomous and cue-directed neuronal differentiation, and following orthotopic transplantation into naïve fetuses, were unable to integrate into neurogenic niches. CD24(depleted) cells retained neurosphere regeneration capacity, but following ethanol exposure, generated increased numbers of CD24(+) cells relative to controls.
Neuronal lineage committed CD24(+) cells exhibit specific vulnerability, and ethanol exposure persistently impairs this population's cell-autonomous differentiation capacity. CD24(+) cells may additionally serve as quorum sensors within neurogenic niches; their loss, leading to compensatory NSC activation, perhaps depleting renewal capacity. These data collectively advance a mechanistic hypothesis for teratogenesis leading to microencephaly.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0069560</identifier><identifier>PMID: 23894503</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adoptive transfer ; Alcohol ; Analysis ; Animal models ; Animals ; Apoptosis ; Biology ; Biomarkers - metabolism ; Brain ; c-Kit protein ; CD24 Antigen - genetics ; CD24 Antigen - metabolism ; Cell Count ; Cell culture ; Cell differentiation ; Cell Differentiation - drug effects ; Cell Lineage - drug effects ; Cell proliferation ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Cytometry ; Differentiation (biology) ; Ethanol ; Ethanol - toxicity ; Exposure ; Female ; Fetus - cytology ; Fetuses ; Flow cytometry ; Forebrain ; Gene Expression Regulation, Developmental - drug effects ; Glial fibrillary acidic protein ; Health aspects ; Kinases ; Lewis X Antigen - metabolism ; Mice ; Mice, Inbred C57BL ; Microencephaly ; MicroRNAs ; Neural stem cells ; Neural Stem Cells - cytology ; Neural Stem Cells - drug effects ; Neural Stem Cells - transplantation ; Neurogenesis ; Neurons ; Neurosciences ; Pregnancy ; Regeneration ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Science ; Stem Cell Transplantation ; Stem cells ; Subpopulations ; Teratogenesis ; Teratogenesis - drug effects ; Teratogenicity ; Teratogens - toxicity ; Therapeutic applications ; Transplantation ; Ultrasound ; Womens health</subject><ispartof>PloS one, 2013-07, Vol.8 (7), p.e69560</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Tingling et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Tingling et al 2013 Tingling et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-94e0ac0c5877c23f903a93dc700f1d0d958ea622bac64e5963dcfea88fbcc5dc3</citedby><cites>FETCH-LOGICAL-c692t-94e0ac0c5877c23f903a93dc700f1d0d958ea622bac64e5963dcfea88fbcc5dc3</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/PMC3718834/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718834/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23847,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23894503$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mezey, Eva</contributor><creatorcontrib>Tingling, Joseph D</creatorcontrib><creatorcontrib>Bake, Shameena</creatorcontrib><creatorcontrib>Holgate, Rhonda</creatorcontrib><creatorcontrib>Rawlings, Jeremy</creatorcontrib><creatorcontrib>Nagsuk, Phillips P</creatorcontrib><creatorcontrib>Chandrasekharan, Jayashree</creatorcontrib><creatorcontrib>Schneider, Sarah L</creatorcontrib><creatorcontrib>Miranda, Rajesh C</creatorcontrib><title>CD24 expression identifies teratogen-sensitive fetal neural stem cell subpopulations: evidence from developmental ethanol exposure and orthotopic cell transfer models</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Ethanol is a potent teratogen. Its adverse neural effects are partly mediated by disrupting fetal neurogenesis. The teratogenic process is poorly understood, and vulnerable neurogenic stages have not been identified. Identifying these is a prerequisite for therapeutic interventions to mitigate effects of teratogen exposures.
We used flow cytometry and qRT-PCR to screen fetal mouse-derived neurosphere cultures for ethanol-sensitive neural stem cell (NSC) subpopulations, to study NSC renewal and differentiation. The identity of vulnerable NSC populations was validated in vivo, using a maternal ethanol exposure model. Finally, the effect of ethanol exposure on the ability of vulnerable NSC subpopulations to integrate into the fetal neurogenic environment was assessed following ultrasound guided, adoptive transfer.
Ethanol decreased NSC mRNAs for c-kit, Musashi-1and GFAP. The CD24(+) NSC population, specifically the CD24(+)CD15(+) double-positive subpopulation, was selectively decreased by ethanol. Maternal ethanol exposure also resulted in decreased fetal forebrain CD24 expression. Ethanol pre-exposed CD24(+) cells exhibited increased proliferation, and deficits in cell-autonomous and cue-directed neuronal differentiation, and following orthotopic transplantation into naïve fetuses, were unable to integrate into neurogenic niches. CD24(depleted) cells retained neurosphere regeneration capacity, but following ethanol exposure, generated increased numbers of CD24(+) cells relative to controls.
Neuronal lineage committed CD24(+) cells exhibit specific vulnerability, and ethanol exposure persistently impairs this population's cell-autonomous differentiation capacity. CD24(+) cells may additionally serve as quorum sensors within neurogenic niches; their loss, leading to compensatory NSC activation, perhaps depleting renewal capacity. These data collectively advance a mechanistic hypothesis for teratogenesis leading to microencephaly.</description><subject>Adoptive transfer</subject><subject>Alcohol</subject><subject>Analysis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biology</subject><subject>Biomarkers - metabolism</subject><subject>Brain</subject><subject>c-Kit protein</subject><subject>CD24 Antigen - genetics</subject><subject>CD24 Antigen - metabolism</subject><subject>Cell Count</subject><subject>Cell culture</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Lineage - drug effects</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Cytometry</subject><subject>Differentiation (biology)</subject><subject>Ethanol</subject><subject>Ethanol - toxicity</subject><subject>Exposure</subject><subject>Female</subject><subject>Fetus - cytology</subject><subject>Fetuses</subject><subject>Flow cytometry</subject><subject>Forebrain</subject><subject>Gene Expression Regulation, Developmental - drug effects</subject><subject>Glial fibrillary acidic protein</subject><subject>Health aspects</subject><subject>Kinases</subject><subject>Lewis X Antigen - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microencephaly</subject><subject>MicroRNAs</subject><subject>Neural stem cells</subject><subject>Neural Stem Cells - cytology</subject><subject>Neural Stem Cells - drug effects</subject><subject>Neural Stem Cells - transplantation</subject><subject>Neurogenesis</subject><subject>Neurons</subject><subject>Neurosciences</subject><subject>Pregnancy</subject><subject>Regeneration</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Science</subject><subject>Stem Cell Transplantation</subject><subject>Stem cells</subject><subject>Subpopulations</subject><subject>Teratogenesis</subject><subject>Teratogenesis - drug effects</subject><subject>Teratogenicity</subject><subject>Teratogens - toxicity</subject><subject>Therapeutic applications</subject><subject>Transplantation</subject><subject>Ultrasound</subject><subject>Womens health</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L3CAUhkNp6W63_QelDRQKvZip0cTEXhSW6dfAwkK_bsWY44yL0ayaYfuH-jvr7GSXCbRQvFD0eV8Pr54se16gZUHq4u2VG70VZjk4C0uEKKsoepCdFozgBcWIPDxan2RPQrhCqCINpY-zE0waVlaInGa_Vx9wmcPN4CEE7WyuO7BRKw0hj-BFdBuwiwA26Kh3kCuIwuQWRp-mEKHPJZi0GtvBDaMRMXmEdzns9j4y8d71eQc7MG7ok3NSQdwK68z-UhdGD7mwXe583LroBi0PhtELGxT4vHcdmPA0e6SECfBsms-yH58-fl99WVxcfl6vzi8WkjIcF6wEJCSSVVPXEhPFEBGMdLJGSBUd6ljVgKAYt0LSEipG05kC0TSqlbLqJDnLXh58B-MCnyIOvChxTWpEyjIR6wPROXHFB6974X9xJzS_3XB-w4WPWhrgEhhQVhZKtqhUVdFUGDPK6grqtm4oTl7vp9vGtodOpnxSrDPT-YnVW75xO57ev2nIvphXk4F31yOE-I-SJ2ojUlXaKpfMZK-D5Odl3RQ0xVMkavkXKo0Oei3TJ1M67c8Eb2aCxES4iRsxhsDX377-P3v5c86-PmK3IEzcBmfG2681B8sDKL0LwYO6T65AfN8jd2nwfY_wqUeS7MVx6veiu6YgfwBMUhFq</recordid><startdate>20130722</startdate><enddate>20130722</enddate><creator>Tingling, Joseph D</creator><creator>Bake, Shameena</creator><creator>Holgate, Rhonda</creator><creator>Rawlings, Jeremy</creator><creator>Nagsuk, Phillips P</creator><creator>Chandrasekharan, Jayashree</creator><creator>Schneider, Sarah L</creator><creator>Miranda, Rajesh C</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>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130722</creationdate><title>CD24 expression identifies teratogen-sensitive fetal neural stem cell subpopulations: evidence from developmental ethanol exposure and orthotopic cell transfer models</title><author>Tingling, Joseph D ; Bake, Shameena ; Holgate, Rhonda ; Rawlings, Jeremy ; Nagsuk, Phillips P ; Chandrasekharan, Jayashree ; Schneider, Sarah L ; Miranda, Rajesh C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-94e0ac0c5877c23f903a93dc700f1d0d958ea622bac64e5963dcfea88fbcc5dc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adoptive transfer</topic><topic>Alcohol</topic><topic>Analysis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biology</topic><topic>Biomarkers - metabolism</topic><topic>Brain</topic><topic>c-Kit protein</topic><topic>CD24 Antigen - genetics</topic><topic>CD24 Antigen - metabolism</topic><topic>Cell Count</topic><topic>Cell culture</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Lineage - drug effects</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Cytometry</topic><topic>Differentiation (biology)</topic><topic>Ethanol</topic><topic>Ethanol - toxicity</topic><topic>Exposure</topic><topic>Female</topic><topic>Fetus - cytology</topic><topic>Fetuses</topic><topic>Flow cytometry</topic><topic>Forebrain</topic><topic>Gene Expression Regulation, Developmental - drug effects</topic><topic>Glial fibrillary acidic protein</topic><topic>Health aspects</topic><topic>Kinases</topic><topic>Lewis X Antigen - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microencephaly</topic><topic>MicroRNAs</topic><topic>Neural stem cells</topic><topic>Neural Stem Cells - cytology</topic><topic>Neural Stem Cells - drug effects</topic><topic>Neural Stem Cells - transplantation</topic><topic>Neurogenesis</topic><topic>Neurons</topic><topic>Neurosciences</topic><topic>Pregnancy</topic><topic>Regeneration</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Science</topic><topic>Stem Cell Transplantation</topic><topic>Stem cells</topic><topic>Subpopulations</topic><topic>Teratogenesis</topic><topic>Teratogenesis - drug effects</topic><topic>Teratogenicity</topic><topic>Teratogens - toxicity</topic><topic>Therapeutic applications</topic><topic>Transplantation</topic><topic>Ultrasound</topic><topic>Womens health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tingling, Joseph D</creatorcontrib><creatorcontrib>Bake, Shameena</creatorcontrib><creatorcontrib>Holgate, Rhonda</creatorcontrib><creatorcontrib>Rawlings, Jeremy</creatorcontrib><creatorcontrib>Nagsuk, Phillips P</creatorcontrib><creatorcontrib>Chandrasekharan, Jayashree</creatorcontrib><creatorcontrib>Schneider, Sarah L</creatorcontrib><creatorcontrib>Miranda, Rajesh C</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: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tingling, Joseph D</au><au>Bake, Shameena</au><au>Holgate, Rhonda</au><au>Rawlings, Jeremy</au><au>Nagsuk, Phillips P</au><au>Chandrasekharan, Jayashree</au><au>Schneider, Sarah L</au><au>Miranda, Rajesh C</au><au>Mezey, Eva</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CD24 expression identifies teratogen-sensitive fetal neural stem cell subpopulations: evidence from developmental ethanol exposure and orthotopic cell transfer models</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-07-22</date><risdate>2013</risdate><volume>8</volume><issue>7</issue><spage>e69560</spage><pages>e69560-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Ethanol is a potent teratogen. Its adverse neural effects are partly mediated by disrupting fetal neurogenesis. The teratogenic process is poorly understood, and vulnerable neurogenic stages have not been identified. Identifying these is a prerequisite for therapeutic interventions to mitigate effects of teratogen exposures.
We used flow cytometry and qRT-PCR to screen fetal mouse-derived neurosphere cultures for ethanol-sensitive neural stem cell (NSC) subpopulations, to study NSC renewal and differentiation. The identity of vulnerable NSC populations was validated in vivo, using a maternal ethanol exposure model. Finally, the effect of ethanol exposure on the ability of vulnerable NSC subpopulations to integrate into the fetal neurogenic environment was assessed following ultrasound guided, adoptive transfer.
Ethanol decreased NSC mRNAs for c-kit, Musashi-1and GFAP. The CD24(+) NSC population, specifically the CD24(+)CD15(+) double-positive subpopulation, was selectively decreased by ethanol. Maternal ethanol exposure also resulted in decreased fetal forebrain CD24 expression. Ethanol pre-exposed CD24(+) cells exhibited increased proliferation, and deficits in cell-autonomous and cue-directed neuronal differentiation, and following orthotopic transplantation into naïve fetuses, were unable to integrate into neurogenic niches. CD24(depleted) cells retained neurosphere regeneration capacity, but following ethanol exposure, generated increased numbers of CD24(+) cells relative to controls.
Neuronal lineage committed CD24(+) cells exhibit specific vulnerability, and ethanol exposure persistently impairs this population's cell-autonomous differentiation capacity. CD24(+) cells may additionally serve as quorum sensors within neurogenic niches; their loss, leading to compensatory NSC activation, perhaps depleting renewal capacity. These data collectively advance a mechanistic hypothesis for teratogenesis leading to microencephaly.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23894503</pmid><doi>10.1371/journal.pone.0069560</doi><tpages>e69560</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2013-07, Vol.8 (7), p.e69560 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1427370344 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
subjects | Adoptive transfer Alcohol Analysis Animal models Animals Apoptosis Biology Biomarkers - metabolism Brain c-Kit protein CD24 Antigen - genetics CD24 Antigen - metabolism Cell Count Cell culture Cell differentiation Cell Differentiation - drug effects Cell Lineage - drug effects Cell proliferation Cell Proliferation - drug effects Cell Survival - drug effects Cytometry Differentiation (biology) Ethanol Ethanol - toxicity Exposure Female Fetus - cytology Fetuses Flow cytometry Forebrain Gene Expression Regulation, Developmental - drug effects Glial fibrillary acidic protein Health aspects Kinases Lewis X Antigen - metabolism Mice Mice, Inbred C57BL Microencephaly MicroRNAs Neural stem cells Neural Stem Cells - cytology Neural Stem Cells - drug effects Neural Stem Cells - transplantation Neurogenesis Neurons Neurosciences Pregnancy Regeneration RNA, Messenger - genetics RNA, Messenger - metabolism Science Stem Cell Transplantation Stem cells Subpopulations Teratogenesis Teratogenesis - drug effects Teratogenicity Teratogens - toxicity Therapeutic applications Transplantation Ultrasound Womens health |
title | CD24 expression identifies teratogen-sensitive fetal neural stem cell subpopulations: evidence from developmental ethanol exposure and orthotopic cell transfer models |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T00%3A41%3A29IST&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=CD24%20expression%20identifies%20teratogen-sensitive%20fetal%20neural%20stem%20cell%20subpopulations:%20evidence%20from%20developmental%20ethanol%20exposure%20and%20orthotopic%20cell%20transfer%20models&rft.jtitle=PloS%20one&rft.au=Tingling,%20Joseph%20D&rft.date=2013-07-22&rft.volume=8&rft.issue=7&rft.spage=e69560&rft.pages=e69560-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0069560&rft_dat=%3Cgale_plos_%3EA478167001%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=1427370344&rft_id=info:pmid/23894503&rft_galeid=A478167001&rft_doaj_id=oai_doaj_org_article_ce9e6941fcb04f51852296975e7b7862&rfr_iscdi=true |