Agonist Antibody Converts Stem Cells into Migrating Brown Adipocyte-Like Cells in Heart

• Published in: Cells (Basel, Switzerland) Vol. 9; no. 1; p. 256
• Main Authors: Han, Kyung Ho, Arlian, Britni M, Lin, Chih-Wei, Jin, Hyun Yong, Kang, Geun-Hyung, Lee, Sahmin, Lee, Peter Chang-Whan, Lerner, Richard A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.01.2020; MDPI
• 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 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; Ligands; Mice; Microscopy; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - ultrastructure; Myocardium; Myocardium - cytology; Myocardium - ultrastructure; Physiology; Proteins; Stem cell transplantation; Stem cells; Stem Cells - cytology; Stem Cells - drug effects; Thermogenesis; Thyroid; Thyroid gland; United States > US; Chicago Illinois; Iodotyrosine Deiodinase (IYD); cell differentiation; antibody; brown adipocyte-like cells
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9010256

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.