Paper Title
THE ROLES OF HISTONE DEACETYLASES IN THE SPHEROID FORMATION OF HUMAN ADIPOSE-DERIVED STEM CELLS

Abstract
Abstract - Adipose-derived stem cells (ASCs), known as multipotent stem cells, are most widely used in clinical application, such as cardiovascularor neuronal-related diseases, in recent years. Adipose tissues have many advantages, e.g. easily harvested and isolated, abundant and easy to culture, as an adult stem cell source compared to bone marrow. Previousworkshave demonstrated a chitosan-contained microenvironment induced spheroid formation and differentiation of ASCs into a mixed population of neural lineage-like cells (NLCs) which poses aneuron differentiation potential andthe nerve regenerative benefit. However, the underline mechanisms of ASC differentiation into NLCs is still unknown.The development and repair of the nervous system requires the coordinated expression of several specific genes. Epigenetic mechanisms regulating gene expression via histones modifications. The post-translational modification of histones by histone acetyltransferases (HATs) and histone deacetylases (HDACs) shapes the chromatin structure to adjust transcriptional factors during neuronal development or regeneration. Recently, increasing observations point out that the histone acetylation and deacetylation play a critical role in the response of neurons to injury. HDACs are known to repress transcription through their deacetylase activity and the interaction with co-repressors in nucleus, however,some of these enzymes are also located in the cytoplasm, display transcription-independent activities by modulating different protein functions.In our observations, during the spheroid formation, HAT activities decreased and HDAC activities increased. The expression of the class I HDAC subtype: HDAC1, HDAC2, HDAC3, which are mainly localized in nuclear, were no different between in hASCs and spheroids. In the class II HDAC subtype, we found the expressions of HDAC4, HDAC5 and pHDAC4/5/7 were increased inspheroids. Furthermore, the class II inhibitors, TMP195, and TMP269 inhibited the spheroid formation and the RNA levels of neuron marker genes (nestin and GFAP) in a dose dependent manner. These results reveal class II HDACsplays an important role as a transcriptional switch controlling in neuron regeneration. Keywords - Adipose-Derived Stem Cells, Spheroid Formation, Class II HDACs, Nerve Regeneration