en Cellular and molecular Neuroscience Cellular and molecular Neuroscience Original Original <span style="font-size:14px;"><span style="font-family:Tahoma;"><strong>Introduction: </strong>Maintenance of neurogenesis depends on the function of some histone-modifying enzymes; including Enhancer of zeste homolog 2 (EZH2) and histone acetyltransferases (P300). The mechanism of epigenetic regulation and gene expression underlying the transition of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) into MNs has not been fully clarified.&nbsp;<br> <strong>Methods: </strong>Two morphogens; sonic hedgehog (Shh: 100 ng/mL) and retinoic acid (RA: 0.01 mM) were involved in the specification of hUCB-MSCs into MNs after MSC characterization using Flow cytometry. Real time-quantitative PCR and immunocytochemistry were performed to find the expression of the genes at the level of mRNA and protein.&nbsp;<br> <strong>Results:</strong> The expression of MN-related markers was confirmed at the level of mRNA and protein by induction of differentiation. The results were confirmed by immunocytochemistry and showed those mean cell percentages of 55.33%&plusmn;15.885% and 49.67%&plusmn;13.796% could express Islet-1 and ChAT, respectively. The gene expression level of Islet-1 and ChAT was significantly increased in the first and second week of exposure, respectively. After two weeks, the expression level of P300 and EZH-2 genes increased remarkably. No significant expression of Mnx-1 was detected when compared to the control sample.<br> <strong>Conclusion:</strong> MN-related markers, Islet-1 and ChAT, were detected in differentiated cells of hUCB-MSCs, supporting the potency of cord blood cells in the regeneration of MN-related disorders. Assessing these epigenetic regulatory genes at the protein level can be suggested to confirm their functional epigenetic modifying effects during motor neuron differentiation.<br> <span style="line-height:200%"><span style="color:#4bacc6"></span></span></span></span> Cord blood, Motor Neuron, P300, EZH-2 709 718 http://bcn.iums.ac.ir/browse.php?a_code=A-10-2997-1&slc_lang=en&sid=1 Marjaneh Motaghed marjanehmd@gmail.com 13700319475328460042828 13700319475328460042828 No Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran. Davood Sanooghi davoodsanoghi@gmail.com 13700319475328460042829 13700319475328460042829 No Department of Genetics, School of Biological Sciences, Shahid Beheshti University, Tehran, Iran. Zohreh Bagher baharebagher@gmail.com 13700319475328460042830 13700319475328460042830 No ENT and Head and Neck Research Center and Department, Five Senses Institute, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran. Faezeh Faghihi faezefaghihi@yahoo.com 13700319475328460042831 13700319475328460042831 Yes Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran. Abolfazl Lotfi Lotfi.A@tvu.ac.ir 13700319475328460042832 13700319475328460042832 No Damavand Agricultural College, Technical and Vocational University, Tehran, Iran. Ali Shahbazi shahbazial@yahoo.com 13700319475328460042833 13700319475328460042833 No Department of Neuroscience, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. Mohammad Taghi Jogataei joghataei.mt@iums.ac.ir 13700319475328460042834 13700319475328460042834 No Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.