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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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Autores principales: Han, Kyung Ho, Arlian, Britni M., Lin, Chih-Wei, Jin, Hyun Yong, Kang, Geun-Hyung, Lee, Sahmin, Lee, Peter Chang-Whan, Lerner, Richard A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017361/
https://www.ncbi.nlm.nih.gov/pubmed/31968623
http://dx.doi.org/10.3390/cells9010256
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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_facet 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 Han, Kyung Ho
collection PubMed
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.
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spelling pubmed-70173612020-02-28 Agonist Antibody Converts Stem Cells into Migrating Brown Adipocyte-Like Cells in Heart Han, Kyung Ho Arlian, Britni M. Lin, Chih-Wei Jin, Hyun Yong Kang, Geun-Hyung Lee, Sahmin Lee, Peter Chang-Whan Lerner, Richard A. Cells Article 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. MDPI 2020-01-20 /pmc/articles/PMC7017361/ /pubmed/31968623 http://dx.doi.org/10.3390/cells9010256 Text en © 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/).
spellingShingle Article
Han, Kyung Ho
Arlian, Britni M.
Lin, Chih-Wei
Jin, Hyun Yong
Kang, Geun-Hyung
Lee, Sahmin
Lee, Peter Chang-Whan
Lerner, Richard A.
Agonist Antibody Converts Stem Cells into Migrating Brown Adipocyte-Like Cells in Heart
title Agonist Antibody Converts Stem Cells into Migrating Brown Adipocyte-Like Cells in Heart
title_full Agonist Antibody Converts Stem Cells into Migrating Brown Adipocyte-Like Cells in Heart
title_fullStr Agonist Antibody Converts Stem Cells into Migrating Brown Adipocyte-Like Cells in Heart
title_full_unstemmed Agonist Antibody Converts Stem Cells into Migrating Brown Adipocyte-Like Cells in Heart
title_short Agonist Antibody Converts Stem Cells into Migrating Brown Adipocyte-Like Cells in Heart
title_sort agonist antibody converts stem cells into migrating brown adipocyte-like cells in heart
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017361/
https://www.ncbi.nlm.nih.gov/pubmed/31968623
http://dx.doi.org/10.3390/cells9010256
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