Agonist Antibody Converts Stem Cells into Migrating Brown Adipocyte-Like Cells in Heart.
Kyung Ho HanBritni M ArlianChih-Wei LinHyun Yong JinGeun-Hyung KangSahmin LeePeter Chang-Whan LeeRichard A LernerPublished in: Cells (2020)
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.
Keyphrases
- stem cells
- induced apoptosis
- bone marrow
- adipose tissue
- cell cycle arrest
- heart failure
- insulin resistance
- cell therapy
- endothelial cells
- mesenchymal stem cells
- fatty acid
- signaling pathway
- cell death
- escherichia coli
- staphylococcus aureus
- metabolic syndrome
- machine learning
- computed tomography
- deep learning
- binding protein
- artificial intelligence
- electronic health record
- highly efficient
- pluripotent stem cells