PMID- 27001466
OWN - NLM
STAT- MEDLINE
DCOM- 20170508
LR  - 20181202
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Linking)
VI  - 343
IP  - 2
DP  - 2016 May 1
TI  - Enhanced expression of hepatocyte-specific microRNAs in valproic acid mediated 
      hepatic trans-differentiation of human umbilical cord derived mesenchymal stem 
      cells.
PG  - 237-247
LID - S0014-4827(16)30056-8 [pii]
LID - 10.1016/j.yexcr.2016.03.015 [doi]
AB  - MicroRNAs (miRNAs) play an important role in the control of cell fate 
      determination during differentiation. In this study, we analyzed the expression 
      pattern of microRNAs (miRNAs) during hepatic trans-differentiation. The protocol 
      employed the use of histone deacetylase inhibitor (HDACI), valproic acid (VPA) to 
      induce hepatic trans-differentiation of human umbilical cord Wharton's jelly 
      derived mesenchymal stem cells (hUC-MSCs). The differentiated hepatocyte like 
      cells (HLCs) from hUC-MSCs shared typical characteristics with mature 
      hepatocytes, including morphology, expression of hepatocyte -specific genes at 
      the molecular and cellular level. Moreover, the functionality of HLCs was 
      confirmed through various liver function tests such as periodic acid-Schiff (PAS) 
      stain for glycogen accumulation, enzyme-linked immunosorbent assay (ELISA) for 
      synthesis of albumin and release of urea. The aim of the present work was to 
      examine the effect of VPA treatment on miRNA expression during hepatic 
      trans-differentiation. The analysis at miRNA level showed that there was a 
      significant increase in expression of miRNAs involved in hepatic differentiation, 
      due to VPA pre-treatment during differentiation. The study, thus demonstrated 
      that improved expression of hepatocyte-specific miRNAs, miR-23b cluster 
      (miR-27b-3p, miR-24-1-5p and miR-23b-3p), miR-30a-5p, miR-26a-5p, miR-148a-3p, 
      miR-192-5p, miR-122-5p due to VPA pre-treatment contributed to a more efficient 
      hepatic trans-differentiation from hUC-MSCs. The putative targets of these 
      upregulated miRNAs were predicted using Bioinformatics analysis. Finally, 
      miR-122-5p, highly upregulated miRNA during hepatic differentiation, was selected 
      for target verification studies. Thus, this study also provides the basis for the 
      function of miR-122-5p during hepatic differentiation of hUC-MSCs.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Raut, Akshata
AU  - Raut A
AD  - Department of Biological Sciences, Sunandan Divatia School of Science, NMIMS 
      University, Vile Parle (West), Mumbai, Maharashtra, India.
FAU - Khanna, Aparna
AU  - Khanna A
AD  - Department of Biological Sciences, Sunandan Divatia School of Science, NMIMS 
      University, Vile Parle (West), Mumbai, Maharashtra, India. Electronic address: 
      aparna.khanna@nmims.edu.
LA  - eng
PT  - Journal Article
DEP - 20160318
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Biomarkers)
RN  - 0 (Histones)
RN  - 0 (MicroRNAs)
RN  - 0 (SOXC Transcription Factors)
RN  - 0 (Vimentin)
RN  - 614OI1Z5WI (Valproic Acid)
SB  - IM
MH  - Acetylation/drug effects
MH  - Biomarkers/metabolism
MH  - Cell Cycle/drug effects
MH  - Cell Separation
MH  - Cell Shape/drug effects
MH  - Cell Transdifferentiation/*drug effects/genetics
MH  - Down-Regulation/drug effects/genetics
MH  - Epigenesis, Genetic/drug effects
MH  - Fluorescent Antibody Technique
MH  - Gene Expression Regulation/*drug effects
MH  - Hepatocytes/drug effects/*metabolism
MH  - Histones/metabolism
MH  - Humans
MH  - Mesenchymal Stem Cells/*cytology/drug effects/metabolism
MH  - MicroRNAs/*genetics/metabolism
MH  - Organ Specificity/drug effects/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Reproducibility of Results
MH  - SOXC Transcription Factors/genetics/metabolism
MH  - Umbilical Cord/*cytology
MH  - Valproic Acid/*pharmacology
MH  - Vimentin/genetics/metabolism
OTO - NOTNLM
OT  - Hepatic differentiation
OT  - Hepatocyte-like cells
OT  - Histone deacetylase inhibitors, Transfection
OT  - Liver disease
OT  - Mesenchymal stem cells
OT  - MicroRNA
OT  - MicroRNA expression profiling
OT  - Umbilical cord
EDAT- 2016/03/24 06:00
MHDA- 2017/05/10 06:00
CRDT- 2016/03/23 06:00
PHST- 2015/12/02 00:00 [received]
PHST- 2016/02/29 00:00 [revised]
PHST- 2016/03/16 00:00 [accepted]
PHST- 2016/03/23 06:00 [entrez]
PHST- 2016/03/24 06:00 [pubmed]
PHST- 2017/05/10 06:00 [medline]
AID - S0014-4827(16)30056-8 [pii]
AID - 10.1016/j.yexcr.2016.03.015 [doi]
PST - ppublish
SO  - Exp Cell Res. 2016 May 1;343(2):237-247. doi: 10.1016/j.yexcr.2016.03.015. Epub 
      2016 Mar 18.