Agonist Antibody Converts Stem Cells into Migrating Brown Adipocyte-Like Cells in Heart
We present data showing that Iodotyrosine Deiodinase (IYD) is a dual-function enzyme acting as a catalyst in metabolism and a receptor for cooperative stem cell differentiation. IYD is present both in thyroid cells where it is critical for scavenging iodine from halogenated by-products of thyroid ho...
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| Veröffentlicht in: | Cells (Basel, Switzerland) Switzerland), 2020-01, Vol.9 (1), p.256, Article 256 |
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| creator | Han, Kyung Ho Arlian, Britni M. Lin, Chih-Wei Jin, Hyun Yong Kang, Geun-Hyung Lee, Sahmin Lee, Peter Chang-Whan Lerner, Richard A. |
| description | We present data showing that Iodotyrosine Deiodinase (IYD) is a dual-function enzyme acting as a catalyst in metabolism and a receptor for cooperative stem cell differentiation. IYD is present both in thyroid cells where it is critical for scavenging iodine from halogenated by-products of thyroid hormone production and on hematopoietic stem cells. To close the cooperative loop, the mono- and di-Iodotyrosine (MIT and DIT) substrates of IYD in the thyroid are also agonists for IYD now acting as a receptor on bone marrow stem cells. While studying intracellular combinatorial antibody libraries, we discovered an agonist antibody, H3 Ab, of which the target is the enzyme IYD. When agonized by H3 Ab, IYD expressed on stem cells induces differentiation of the cells into brown adipocyte-like cells, which selectively migrate to mouse heart tissue. H3 Ab also binds to IYD expressed on human myocardium. Thus, one has a single enzyme acting in different ways on different cells for the cooperative purpose of enhancing thermogenesis or of regenerating damaged heart tissue. |
| doi_str_mv | 10.3390/cells9010256 |
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IYD is present both in thyroid cells where it is critical for scavenging iodine from halogenated by-products of thyroid hormone production and on hematopoietic stem cells. To close the cooperative loop, the mono- and di-Iodotyrosine (MIT and DIT) substrates of IYD in the thyroid are also agonists for IYD now acting as a receptor on bone marrow stem cells. While studying intracellular combinatorial antibody libraries, we discovered an agonist antibody, H3 Ab, of which the target is the enzyme IYD. When agonized by H3 Ab, IYD expressed on stem cells induces differentiation of the cells into brown adipocyte-like cells, which selectively migrate to mouse heart tissue. H3 Ab also binds to IYD expressed on human myocardium. Thus, one has a single enzyme acting in different ways on different cells for the cooperative purpose of enhancing thermogenesis or of regenerating damaged heart tissue.</description><identifier>ISSN: 2073-4409</identifier><identifier>EISSN: 2073-4409</identifier><identifier>DOI: 10.3390/cells9010256</identifier><identifier>PMID: 31968623</identifier><language>eng</language><publisher>BASEL: Mdpi</publisher><subject>Adipocytes ; Adipocytes, Brown - cytology ; Adipocytes, Brown - drug effects ; Adipocytes, Brown - ultrastructure ; Agonists ; Animals ; Antibodies ; Antibodies - pharmacology ; antibody ; Antibody libraries ; Bone marrow ; brown adipocyte-like cells ; Catalysts ; Cell Biology ; Cell differentiation ; Cell Differentiation - drug effects ; Cell migration ; Cell Movement - drug effects ; Enzymes ; Flow cytometry ; Gene expression ; Heart ; Hematopoietic stem cells ; Humans ; Iodide peroxidase ; Iodine ; iodotyrosine deiodinase (iyd) ; Laboratories ; Life Sciences & Biomedicine ; Ligands ; Mice ; Microscopy ; Mitochondria - drug effects ; Mitochondria - metabolism ; Mitochondria - ultrastructure ; Myocardium ; Myocardium - cytology ; Myocardium - ultrastructure ; Physiology ; Proteins ; Science & Technology ; Stem cell transplantation ; Stem cells ; Stem Cells - cytology ; Stem Cells - drug effects ; Thermogenesis ; Thyroid ; Thyroid gland</subject><ispartof>Cells (Basel, Switzerland), 2020-01, Vol.9 (1), p.256, Article 256</ispartof><rights>2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>7</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000515398200255</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c478t-26e36fd53713f67ed3d0c0f7d8c5f89d0894f254c69d6d9877851119d01bfcdb3</citedby><cites>FETCH-LOGICAL-c478t-26e36fd53713f67ed3d0c0f7d8c5f89d0894f254c69d6d9877851119d01bfcdb3</cites><orcidid>0000-0002-2320-6365 ; 0000-0001-6907-1462</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017361/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017361/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2115,27928,27929,53795,53797</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31968623$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Han, Kyung Ho</creatorcontrib><creatorcontrib>Arlian, Britni M.</creatorcontrib><creatorcontrib>Lin, Chih-Wei</creatorcontrib><creatorcontrib>Jin, Hyun Yong</creatorcontrib><creatorcontrib>Kang, Geun-Hyung</creatorcontrib><creatorcontrib>Lee, Sahmin</creatorcontrib><creatorcontrib>Lee, Peter Chang-Whan</creatorcontrib><creatorcontrib>Lerner, Richard A.</creatorcontrib><title>Agonist Antibody Converts Stem Cells into Migrating Brown Adipocyte-Like Cells in Heart</title><title>Cells (Basel, Switzerland)</title><addtitle>CELLS-BASEL</addtitle><addtitle>Cells</addtitle><description>We present data showing that Iodotyrosine Deiodinase (IYD) is a dual-function enzyme acting as a catalyst in metabolism and a receptor for cooperative stem cell differentiation. IYD is present both in thyroid cells where it is critical for scavenging iodine from halogenated by-products of thyroid hormone production and on hematopoietic stem cells. To close the cooperative loop, the mono- and di-Iodotyrosine (MIT and DIT) substrates of IYD in the thyroid are also agonists for IYD now acting as a receptor on bone marrow stem cells. While studying intracellular combinatorial antibody libraries, we discovered an agonist antibody, H3 Ab, of which the target is the enzyme IYD. When agonized by H3 Ab, IYD expressed on stem cells induces differentiation of the cells into brown adipocyte-like cells, which selectively migrate to mouse heart tissue. H3 Ab also binds to IYD expressed on human myocardium. Thus, one has a single enzyme acting in different ways on different cells for the cooperative purpose of enhancing thermogenesis or of regenerating damaged heart tissue.</description><subject>Adipocytes</subject><subject>Adipocytes, Brown - cytology</subject><subject>Adipocytes, Brown - drug effects</subject><subject>Adipocytes, Brown - ultrastructure</subject><subject>Agonists</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies - pharmacology</subject><subject>antibody</subject><subject>Antibody libraries</subject><subject>Bone marrow</subject><subject>brown adipocyte-like cells</subject><subject>Catalysts</subject><subject>Cell Biology</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell migration</subject><subject>Cell Movement - drug effects</subject><subject>Enzymes</subject><subject>Flow cytometry</subject><subject>Gene expression</subject><subject>Heart</subject><subject>Hematopoietic stem cells</subject><subject>Humans</subject><subject>Iodide peroxidase</subject><subject>Iodine</subject><subject>iodotyrosine deiodinase (iyd)</subject><subject>Laboratories</subject><subject>Life Sciences & Biomedicine</subject><subject>Ligands</subject><subject>Mice</subject><subject>Microscopy</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondria - ultrastructure</subject><subject>Myocardium</subject><subject>Myocardium - cytology</subject><subject>Myocardium - ultrastructure</subject><subject>Physiology</subject><subject>Proteins</subject><subject>Science & Technology</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - drug effects</subject><subject>Thermogenesis</subject><subject>Thyroid</subject><subject>Thyroid gland</subject><issn>2073-4409</issn><issn>2073-4409</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkk1v1DAQhiMEolXpjTOKxAUJQu34-4K0RNBWWtQDII5W4o_gJWsvttNq_z1etl1tOeGLR55n3pnxTFW9hOA9QgJcKDNNSQAIWkKfVKctYKjBGIinR_ZJdZ7SCpTDIYWAPK9OEBSU0xadVj8WY_Au5XrhsxuC3tZd8Lcm5lR_zWZdd7sEtfM51F_cGPvs_Fh_jOHO1wvtNkFts2mW7pc5kPWV6WN-UT2z_ZTM-f19Vn3__Olbd9Usby6vu8WyUZjx3LTUIGo1QQwiS5nRSAMFLNNcEcuFBlxg2xKsqNBUC84YJxDC4oCDVXpAZ9X1XleHfiU30a37uJWhd_LvQ4ijLNU4NRlpEbKIQ1bSYUzRzgRqUIANDGoObNH6sNfazMPaaGV8jv30SPSxx7ufcgy3kgHIEIVF4M29QAy_Z5OyXLu0G1HvTZiTbBHGbZkU5AV9_Q-6CnP05atkaZcXNcpAod7tKRVDStHYQzEQyN0CyOMFKPir4wYO8MO4C8D3wJ0Zgk3KGa_MASsbQiBBgregyJHO5TLu4Lsw-1xC3_5_KPoDzdDLzA</recordid><startdate>20200120</startdate><enddate>20200120</enddate><creator>Han, Kyung Ho</creator><creator>Arlian, Britni M.</creator><creator>Lin, Chih-Wei</creator><creator>Jin, Hyun Yong</creator><creator>Kang, Geun-Hyung</creator><creator>Lee, Sahmin</creator><creator>Lee, Peter Chang-Whan</creator><creator>Lerner, Richard A.</creator><general>Mdpi</general><general>MDPI AG</general><general>MDPI</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><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>8FD</scope><scope>8FE</scope><scope>8FH</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>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-2320-6365</orcidid><orcidid>https://orcid.org/0000-0001-6907-1462</orcidid></search><sort><creationdate>20200120</creationdate><title>Agonist Antibody Converts Stem Cells into Migrating Brown Adipocyte-Like Cells in Heart</title><author>Han, Kyung Ho ; Arlian, Britni M. ; Lin, Chih-Wei ; Jin, Hyun Yong ; Kang, Geun-Hyung ; Lee, Sahmin ; Lee, Peter Chang-Whan ; Lerner, Richard A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-26e36fd53713f67ed3d0c0f7d8c5f89d0894f254c69d6d9877851119d01bfcdb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adipocytes</topic><topic>Adipocytes, Brown - cytology</topic><topic>Adipocytes, Brown - drug effects</topic><topic>Adipocytes, Brown - ultrastructure</topic><topic>Agonists</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies - pharmacology</topic><topic>antibody</topic><topic>Antibody libraries</topic><topic>Bone marrow</topic><topic>brown adipocyte-like cells</topic><topic>Catalysts</topic><topic>Cell Biology</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell migration</topic><topic>Cell Movement - drug effects</topic><topic>Enzymes</topic><topic>Flow cytometry</topic><topic>Gene expression</topic><topic>Heart</topic><topic>Hematopoietic stem cells</topic><topic>Humans</topic><topic>Iodide peroxidase</topic><topic>Iodine</topic><topic>iodotyrosine deiodinase (iyd)</topic><topic>Laboratories</topic><topic>Life Sciences & Biomedicine</topic><topic>Ligands</topic><topic>Mice</topic><topic>Microscopy</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Mitochondria - ultrastructure</topic><topic>Myocardium</topic><topic>Myocardium - cytology</topic><topic>Myocardium - ultrastructure</topic><topic>Physiology</topic><topic>Proteins</topic><topic>Science & Technology</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - drug effects</topic><topic>Thermogenesis</topic><topic>Thyroid</topic><topic>Thyroid gland</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Han, Kyung Ho</creatorcontrib><creatorcontrib>Arlian, Britni M.</creatorcontrib><creatorcontrib>Lin, Chih-Wei</creatorcontrib><creatorcontrib>Jin, Hyun Yong</creatorcontrib><creatorcontrib>Kang, Geun-Hyung</creatorcontrib><creatorcontrib>Lee, Sahmin</creatorcontrib><creatorcontrib>Lee, Peter Chang-Whan</creatorcontrib><creatorcontrib>Lerner, Richard A.</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Access via ProQuest (Open Access)</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>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Cells (Basel, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Han, Kyung Ho</au><au>Arlian, Britni M.</au><au>Lin, Chih-Wei</au><au>Jin, Hyun Yong</au><au>Kang, Geun-Hyung</au><au>Lee, Sahmin</au><au>Lee, Peter Chang-Whan</au><au>Lerner, Richard A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Agonist Antibody Converts Stem Cells into Migrating Brown Adipocyte-Like Cells in Heart</atitle><jtitle>Cells (Basel, Switzerland)</jtitle><stitle>CELLS-BASEL</stitle><addtitle>Cells</addtitle><date>2020-01-20</date><risdate>2020</risdate><volume>9</volume><issue>1</issue><spage>256</spage><pages>256-</pages><artnum>256</artnum><issn>2073-4409</issn><eissn>2073-4409</eissn><abstract>We present data showing that Iodotyrosine Deiodinase (IYD) is a dual-function enzyme acting as a catalyst in metabolism and a receptor for cooperative stem cell differentiation. IYD is present both in thyroid cells where it is critical for scavenging iodine from halogenated by-products of thyroid hormone production and on hematopoietic stem cells. To close the cooperative loop, the mono- and di-Iodotyrosine (MIT and DIT) substrates of IYD in the thyroid are also agonists for IYD now acting as a receptor on bone marrow stem cells. While studying intracellular combinatorial antibody libraries, we discovered an agonist antibody, H3 Ab, of which the target is the enzyme IYD. When agonized by H3 Ab, IYD expressed on stem cells induces differentiation of the cells into brown adipocyte-like cells, which selectively migrate to mouse heart tissue. H3 Ab also binds to IYD expressed on human myocardium. Thus, one has a single enzyme acting in different ways on different cells for the cooperative purpose of enhancing thermogenesis or of regenerating damaged heart tissue.</abstract><cop>BASEL</cop><pub>Mdpi</pub><pmid>31968623</pmid><doi>10.3390/cells9010256</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-2320-6365</orcidid><orcidid>https://orcid.org/0000-0001-6907-1462</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adipocytes Adipocytes, Brown - cytology Adipocytes, Brown - drug effects Adipocytes, Brown - ultrastructure Agonists Animals Antibodies Antibodies - pharmacology antibody Antibody libraries Bone marrow brown adipocyte-like cells Catalysts Cell Biology Cell differentiation Cell Differentiation - drug effects Cell migration Cell Movement - drug effects Enzymes Flow cytometry Gene expression Heart Hematopoietic stem cells Humans Iodide peroxidase Iodine iodotyrosine deiodinase (iyd) Laboratories Life Sciences & Biomedicine Ligands Mice Microscopy Mitochondria - drug effects Mitochondria - metabolism Mitochondria - ultrastructure Myocardium Myocardium - cytology Myocardium - ultrastructure Physiology Proteins Science & Technology Stem cell transplantation Stem cells Stem Cells - cytology Stem Cells - drug effects Thermogenesis Thyroid Thyroid gland |
| title | Agonist Antibody Converts Stem Cells into Migrating Brown Adipocyte-Like Cells in Heart |
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