Stress Decreases Host Viral Resistance and Increases Covid Susceptibility in Embryonic Stem Cells
Stress-induced changes in viral receptor and susceptibility gene expression were measured in embryonic stem cells (ESC) and differentiated progeny. Rex1 promoter-Red Fluorescence Protein reporter ESC were tested by RNAseq after 72hr exposures to control stress hyperosmotic sorbitol under stemness cu...
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| creator | Abdulhasan, Mohammed Ruden, Ximena Rappolee, Benjamin Dutta, Sudipta Gurdziel, Katherine Ruden, Douglas M. Awonuga, Awoniyi O Korzeniewski, Steve J. Puscheck, Elizabeth E. Rappolee, Daniel A. |
| description | Stress-induced changes in viral receptor and susceptibility gene expression were measured in embryonic stem cells (ESC) and differentiated progeny. Rex1 promoter-Red Fluorescence Protein reporter ESC were tested by RNAseq after 72hr exposures to control stress hyperosmotic sorbitol under stemness culture (NS) to quantify stress-forced differentiation (SFD) transcriptomic programs. Control ESC cultured with stemness factor removal produced normal differentiation (ND). Bulk RNAseq transcriptomic analysis showed significant upregulation of two genes involved in Covid-19 cell uptake, Vimentin (VIM) and Transmembrane Serine Protease 2 (TMPRSS2). SFD increased the hepatitis A virus receptor (Havcr1) and the transplacental Herpes simplex 1 (HSV1) virus receptor (Pvrl1) compared with ESC undergoing ND. Several other coronavirus receptors, Glutamyl Aminopeptidase (ENPEP) and Dipeptidyl Peptidase 4 (DPP4) were upregulated significantly in SFD>ND. Although stressed ESC are more susceptible to infection due to increased expression of viral receptors and decreased resistance, the necessary Covid-19 receptor, angiotensin converting enzyme (ACE)2, was not expressed in our experiments. TMPRSS2, ENPEP, and DPP4 mediate Coronavirus uptake, but are also markers of extra-embryonic endoderm (XEN), which arise from ESC undergoing ND or SFD. Mouse and human ESCs differentiated to XEN increase TMPRSS2 and other Covid-19 uptake-mediating gene expression, but only some lines express ACE2. Covid-19 susceptibility appears to be genotype-specific and not ubiquitous. Of the 30 gene ontology (GO) groups for viral susceptibility, 15 underwent significant stress-forced changes. Of these, 4 GO groups mediated negative viral regulation and most genes in these increase in ND and decrease with SFD, thus suggesting that stress increases ESC viral susceptibility. Taken together, the data suggest that a control hyperosmotic stress can increase Covid-19 susceptibility and decrease viral host resistance in mouse ESC. However, this limited pilot study should be followed with studies in human ESC, tests of environmental, hormonal, and pharmaceutical stressors and direct tests for infection of stressed, cultured ESC and embryos by Covid-19.
Graphical Abstract |
| doi_str_mv | 10.1007/s12015-021-10188-w |
| format | Article |
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Graphical Abstract</description><identifier>ISSN: 2629-3269</identifier><identifier>ISSN: 2629-3277</identifier><identifier>EISSN: 2629-3277</identifier><identifier>DOI: 10.1007/s12015-021-10188-w</identifier><identifier>PMID: 34155611</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>ACE2 ; Aminopeptidase ; Angiotensin ; Angiotensin-converting enzyme 2 ; Animals ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Cell Biology ; Cell culture ; Cell differentiation ; Cell Differentiation - genetics ; Cells, Cultured ; Coronaviruses ; COVID-19 ; COVID-19 - genetics ; COVID-19 - virology ; Dipeptidyl-peptidase IV ; Embryo cells ; Endoderm ; Gene expression ; Gene Expression - genetics ; Gene regulation ; Genotypes ; Glutamyl aminopeptidase ; Hepatitis A ; Herpes simplex ; Host Microbial Interactions - genetics ; Humans ; Life Sciences ; Mice ; Mouse Embryonic Stem Cells - virology ; Peptidase ; Peptidyl-dipeptidase A ; Pilot Projects ; Promoter Regions, Genetic - genetics ; Regenerative Medicine/Tissue Engineering ; SARS-CoV-2 - pathogenicity ; Sorbitol ; Stem cell transplantation ; Stem Cells ; Susceptibility ; Transcriptomics ; Vimentin</subject><ispartof>Stem cell reviews and reports, 2021-12, Vol.17 (6), p.2164-2177</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-d9721dde2edb2a42062ece6f32677b3dd752ae09f4591defaf6b2e3695b87d3f3</citedby><cites>FETCH-LOGICAL-c474t-d9721dde2edb2a42062ece6f32677b3dd752ae09f4591defaf6b2e3695b87d3f3</cites><orcidid>0000-0001-9276-7521</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12015-021-10188-w$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12015-021-10188-w$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34155611$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abdulhasan, Mohammed</creatorcontrib><creatorcontrib>Ruden, Ximena</creatorcontrib><creatorcontrib>Rappolee, Benjamin</creatorcontrib><creatorcontrib>Dutta, Sudipta</creatorcontrib><creatorcontrib>Gurdziel, Katherine</creatorcontrib><creatorcontrib>Ruden, Douglas M.</creatorcontrib><creatorcontrib>Awonuga, Awoniyi O</creatorcontrib><creatorcontrib>Korzeniewski, Steve J.</creatorcontrib><creatorcontrib>Puscheck, Elizabeth E.</creatorcontrib><creatorcontrib>Rappolee, Daniel A.</creatorcontrib><title>Stress Decreases Host Viral Resistance and Increases Covid Susceptibility in Embryonic Stem Cells</title><title>Stem cell reviews and reports</title><addtitle>Stem Cell Rev and Rep</addtitle><addtitle>Stem Cell Rev Rep</addtitle><description>Stress-induced changes in viral receptor and susceptibility gene expression were measured in embryonic stem cells (ESC) and differentiated progeny. Rex1 promoter-Red Fluorescence Protein reporter ESC were tested by RNAseq after 72hr exposures to control stress hyperosmotic sorbitol under stemness culture (NS) to quantify stress-forced differentiation (SFD) transcriptomic programs. Control ESC cultured with stemness factor removal produced normal differentiation (ND). Bulk RNAseq transcriptomic analysis showed significant upregulation of two genes involved in Covid-19 cell uptake, Vimentin (VIM) and Transmembrane Serine Protease 2 (TMPRSS2). SFD increased the hepatitis A virus receptor (Havcr1) and the transplacental Herpes simplex 1 (HSV1) virus receptor (Pvrl1) compared with ESC undergoing ND. Several other coronavirus receptors, Glutamyl Aminopeptidase (ENPEP) and Dipeptidyl Peptidase 4 (DPP4) were upregulated significantly in SFD>ND. Although stressed ESC are more susceptible to infection due to increased expression of viral receptors and decreased resistance, the necessary Covid-19 receptor, angiotensin converting enzyme (ACE)2, was not expressed in our experiments. TMPRSS2, ENPEP, and DPP4 mediate Coronavirus uptake, but are also markers of extra-embryonic endoderm (XEN), which arise from ESC undergoing ND or SFD. Mouse and human ESCs differentiated to XEN increase TMPRSS2 and other Covid-19 uptake-mediating gene expression, but only some lines express ACE2. Covid-19 susceptibility appears to be genotype-specific and not ubiquitous. Of the 30 gene ontology (GO) groups for viral susceptibility, 15 underwent significant stress-forced changes. Of these, 4 GO groups mediated negative viral regulation and most genes in these increase in ND and decrease with SFD, thus suggesting that stress increases ESC viral susceptibility. Taken together, the data suggest that a control hyperosmotic stress can increase Covid-19 susceptibility and decrease viral host resistance in mouse ESC. However, this limited pilot study should be followed with studies in human ESC, tests of environmental, hormonal, and pharmaceutical stressors and direct tests for infection of stressed, cultured ESC and embryos by Covid-19.
Graphical Abstract</description><subject>ACE2</subject><subject>Aminopeptidase</subject><subject>Angiotensin</subject><subject>Angiotensin-converting enzyme 2</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Cell Biology</subject><subject>Cell culture</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - genetics</subject><subject>Cells, Cultured</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>COVID-19 - genetics</subject><subject>COVID-19 - virology</subject><subject>Dipeptidyl-peptidase IV</subject><subject>Embryo cells</subject><subject>Endoderm</subject><subject>Gene expression</subject><subject>Gene Expression - genetics</subject><subject>Gene regulation</subject><subject>Genotypes</subject><subject>Glutamyl aminopeptidase</subject><subject>Hepatitis A</subject><subject>Herpes simplex</subject><subject>Host Microbial Interactions - genetics</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Mice</subject><subject>Mouse Embryonic Stem Cells - virology</subject><subject>Peptidase</subject><subject>Peptidyl-dipeptidase A</subject><subject>Pilot Projects</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Regenerative Medicine/Tissue Engineering</subject><subject>SARS-CoV-2 - pathogenicity</subject><subject>Sorbitol</subject><subject>Stem cell transplantation</subject><subject>Stem Cells</subject><subject>Susceptibility</subject><subject>Transcriptomics</subject><subject>Vimentin</subject><issn>2629-3269</issn><issn>2629-3277</issn><issn>2629-3277</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kc1u1DAUhS0EolXpC3SBLLFhE_BPYicbJDQttFKlSgx0aznxTXGV2IOv02reHsO0A2XBypbud47v8SHkhLN3nDH9HrlgvKmY4BVnvG2r-2fkUCjRVVJo_Xx_V90BOUa8ZYwJyeqieUkOZM2bRnF-SOw6J0CkpzAksAhIzyNmeu2TnegXQI_ZhgGoDY5ehEdmFe-8o-sFB9hk3_vJ5y31gZ7NfdrG4Ae6zjDTFUwTviIvRjshHD-cR-Tbp7Ovq_Pq8urzxerjZTXUus6V67TgzoEA1wtbC6YEDKDGkkDrXjqnG2GBdWPddNzBaEfVC5Cqa_pWOznKI_Jh57tZ-hncACGXDGaT_GzT1kTrzdNJ8N_NTbwzreCqaVUxePtgkOKPBTCb2ZeA02QDxAWNaOrybV3bdgV98w96G5cUSrxCda1kooQplNhRQ4qICcb9MpyZXyWaXYmmlGh-l2jui-j13zH2ksfKCiB3AJZRuIH05-3_2P4EbBupkA</recordid><startdate>20211201</startdate><enddate>20211201</enddate><creator>Abdulhasan, Mohammed</creator><creator>Ruden, Ximena</creator><creator>Rappolee, Benjamin</creator><creator>Dutta, Sudipta</creator><creator>Gurdziel, Katherine</creator><creator>Ruden, Douglas M.</creator><creator>Awonuga, Awoniyi O</creator><creator>Korzeniewski, Steve J.</creator><creator>Puscheck, Elizabeth E.</creator><creator>Rappolee, Daniel A.</creator><general>Springer US</general><general>Springer Nature B.V</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>7T5</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</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>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9276-7521</orcidid></search><sort><creationdate>20211201</creationdate><title>Stress Decreases Host Viral Resistance and Increases Covid Susceptibility in Embryonic Stem Cells</title><author>Abdulhasan, Mohammed ; Ruden, Ximena ; Rappolee, Benjamin ; Dutta, Sudipta ; Gurdziel, Katherine ; Ruden, Douglas M. ; Awonuga, Awoniyi O ; Korzeniewski, Steve J. ; Puscheck, Elizabeth E. ; Rappolee, Daniel A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-d9721dde2edb2a42062ece6f32677b3dd752ae09f4591defaf6b2e3695b87d3f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>ACE2</topic><topic>Aminopeptidase</topic><topic>Angiotensin</topic><topic>Angiotensin-converting enzyme 2</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Cell Biology</topic><topic>Cell culture</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - genetics</topic><topic>Cells, Cultured</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>COVID-19 - genetics</topic><topic>COVID-19 - virology</topic><topic>Dipeptidyl-peptidase IV</topic><topic>Embryo cells</topic><topic>Endoderm</topic><topic>Gene expression</topic><topic>Gene Expression - genetics</topic><topic>Gene regulation</topic><topic>Genotypes</topic><topic>Glutamyl aminopeptidase</topic><topic>Hepatitis A</topic><topic>Herpes simplex</topic><topic>Host Microbial Interactions - genetics</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Mice</topic><topic>Mouse Embryonic Stem Cells - virology</topic><topic>Peptidase</topic><topic>Peptidyl-dipeptidase A</topic><topic>Pilot Projects</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Regenerative Medicine/Tissue Engineering</topic><topic>SARS-CoV-2 - pathogenicity</topic><topic>Sorbitol</topic><topic>Stem cell transplantation</topic><topic>Stem Cells</topic><topic>Susceptibility</topic><topic>Transcriptomics</topic><topic>Vimentin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abdulhasan, Mohammed</creatorcontrib><creatorcontrib>Ruden, Ximena</creatorcontrib><creatorcontrib>Rappolee, Benjamin</creatorcontrib><creatorcontrib>Dutta, Sudipta</creatorcontrib><creatorcontrib>Gurdziel, Katherine</creatorcontrib><creatorcontrib>Ruden, Douglas M.</creatorcontrib><creatorcontrib>Awonuga, Awoniyi O</creatorcontrib><creatorcontrib>Korzeniewski, Steve J.</creatorcontrib><creatorcontrib>Puscheck, Elizabeth E.</creatorcontrib><creatorcontrib>Rappolee, Daniel 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>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</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>Technology Research Database</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</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>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Stem cell reviews and reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abdulhasan, Mohammed</au><au>Ruden, Ximena</au><au>Rappolee, Benjamin</au><au>Dutta, Sudipta</au><au>Gurdziel, Katherine</au><au>Ruden, Douglas M.</au><au>Awonuga, Awoniyi O</au><au>Korzeniewski, Steve J.</au><au>Puscheck, Elizabeth E.</au><au>Rappolee, Daniel A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stress Decreases Host Viral Resistance and Increases Covid Susceptibility in Embryonic Stem Cells</atitle><jtitle>Stem cell reviews and reports</jtitle><stitle>Stem Cell Rev and Rep</stitle><addtitle>Stem Cell Rev Rep</addtitle><date>2021-12-01</date><risdate>2021</risdate><volume>17</volume><issue>6</issue><spage>2164</spage><epage>2177</epage><pages>2164-2177</pages><issn>2629-3269</issn><issn>2629-3277</issn><eissn>2629-3277</eissn><abstract>Stress-induced changes in viral receptor and susceptibility gene expression were measured in embryonic stem cells (ESC) and differentiated progeny. Rex1 promoter-Red Fluorescence Protein reporter ESC were tested by RNAseq after 72hr exposures to control stress hyperosmotic sorbitol under stemness culture (NS) to quantify stress-forced differentiation (SFD) transcriptomic programs. Control ESC cultured with stemness factor removal produced normal differentiation (ND). Bulk RNAseq transcriptomic analysis showed significant upregulation of two genes involved in Covid-19 cell uptake, Vimentin (VIM) and Transmembrane Serine Protease 2 (TMPRSS2). SFD increased the hepatitis A virus receptor (Havcr1) and the transplacental Herpes simplex 1 (HSV1) virus receptor (Pvrl1) compared with ESC undergoing ND. Several other coronavirus receptors, Glutamyl Aminopeptidase (ENPEP) and Dipeptidyl Peptidase 4 (DPP4) were upregulated significantly in SFD>ND. Although stressed ESC are more susceptible to infection due to increased expression of viral receptors and decreased resistance, the necessary Covid-19 receptor, angiotensin converting enzyme (ACE)2, was not expressed in our experiments. TMPRSS2, ENPEP, and DPP4 mediate Coronavirus uptake, but are also markers of extra-embryonic endoderm (XEN), which arise from ESC undergoing ND or SFD. Mouse and human ESCs differentiated to XEN increase TMPRSS2 and other Covid-19 uptake-mediating gene expression, but only some lines express ACE2. Covid-19 susceptibility appears to be genotype-specific and not ubiquitous. Of the 30 gene ontology (GO) groups for viral susceptibility, 15 underwent significant stress-forced changes. Of these, 4 GO groups mediated negative viral regulation and most genes in these increase in ND and decrease with SFD, thus suggesting that stress increases ESC viral susceptibility. Taken together, the data suggest that a control hyperosmotic stress can increase Covid-19 susceptibility and decrease viral host resistance in mouse ESC. However, this limited pilot study should be followed with studies in human ESC, tests of environmental, hormonal, and pharmaceutical stressors and direct tests for infection of stressed, cultured ESC and embryos by Covid-19.
Graphical Abstract</abstract><cop>New York</cop><pub>Springer US</pub><pmid>34155611</pmid><doi>10.1007/s12015-021-10188-w</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-9276-7521</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2629-3269 |
| ispartof | Stem cell reviews and reports, 2021-12, Vol.17 (6), p.2164-2177 |
| issn | 2629-3269 2629-3277 2629-3277 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8216586 |
| source | MEDLINE; Springer Online Journals Complete |
| subjects | ACE2 Aminopeptidase Angiotensin Angiotensin-converting enzyme 2 Animals Biomedical and Life Sciences Biomedical Engineering and Bioengineering Cell Biology Cell culture Cell differentiation Cell Differentiation - genetics Cells, Cultured Coronaviruses COVID-19 COVID-19 - genetics COVID-19 - virology Dipeptidyl-peptidase IV Embryo cells Endoderm Gene expression Gene Expression - genetics Gene regulation Genotypes Glutamyl aminopeptidase Hepatitis A Herpes simplex Host Microbial Interactions - genetics Humans Life Sciences Mice Mouse Embryonic Stem Cells - virology Peptidase Peptidyl-dipeptidase A Pilot Projects Promoter Regions, Genetic - genetics Regenerative Medicine/Tissue Engineering SARS-CoV-2 - pathogenicity Sorbitol Stem cell transplantation Stem Cells Susceptibility Transcriptomics Vimentin |
| title | Stress Decreases Host Viral Resistance and Increases Covid Susceptibility in Embryonic Stem Cells |
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