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

Kyung Ho Han,Richard A Lerner,Hyun Yong Jin,Britni M Arlian,Geun-Hyung Kang,Peter Chang-Whan Lee,Sahmin Lee,Chih-Wei Lin

doi:10.3390/cells9010256

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.

Highlights

An organism is an amalgamation of different cell types that collectively regulate all of its functions.Each cell type operates by using a different set of molecules of which the output becomes part of the collective function of the organism
The H3 antibody (H3 Ab) gene was isolated for further study, since it was seen five times in cells that trafficked to the heart
The analysis showed that the treated cells had a characteristic adipocyte mRNA expression profile with comparable relative mRNA levels of brown adipocyte (UCP1, PGC1A, and PRDM16) and general adipocyte (AP2, adipoQ, and PPARG) gene markers. (F) Brown and general adipocyte gene expression as determined by RNA sequencing analysis: The hierarchal clustering heat map demonstrates a unique expression pattern in the H3 Ab-treated cells when compared to isotype Ab-treated cells

Summary

Introduction

An organism is an amalgamation of different cell types that collectively regulate all of its functions.Each cell type operates by using a different set of molecules of which the output becomes part of the collective function of the organism. Each cell has a special task of which the nature is determined by its differentiated state Another level of efficiency could be achieved if proteins could have multiple functions that were involved synergistically in both the chemistry and biology of a physiological task. An enzyme could be used for chemical transformations and could serve as a receptor for the differentiation of new cells with synergistic capabilities. We discovered such a dual-function enzyme while studying intracellular combinatorial antibody libraries that regulate cell fates, when autocrine selections are used [1,2,3,4,5,6].

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