Please use this identifier to cite or link to this item: https://doi.org/10.1186/1477-5956-9-3
Title: Cardiogenol C can induce Mouse Hair Bulge Progenitor Cells to Transdifferentiate into Cardiomyocyte-like Cells
Authors: Yau, W.W.Y 
Tang, M.K
Chen, E
YaoYao, Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, Hong Kong
Wong, I.W.C
Lee, H.S.S
Lee, K.K.H
Keywords: cardiogenol c
muscle protein
myosin heavy chain
pyrimidine derivative
transcription factor GATA 4
transcription factor Nkx2.5
transcription factor TBX5
troponin I
unclassified drug
valproic acid
Wnt protein
animal experiment
animal model
article
cardiomyocyte like cell
cell culture
cell differentiation
cell maturation
chromatin
controlled study
hair bulge progenitor cell
heart muscle cell
male
mouse
multipotent stem cell
nonhuman
protein analysis
protein expression
proteomics
signal transduction
skeletal muscle
upregulation
Mus
Issue Date: 2011
Citation: Yau, W.W.Y, Tang, M.K, Chen, E, YaoYao, Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, Hong Kong, Wong, I.W.C, Lee, H.S.S, Lee, K.K.H (2011). Cardiogenol C can induce Mouse Hair Bulge Progenitor Cells to Transdifferentiate into Cardiomyocyte-like Cells. Proteome Science 9 : 3. ScholarBank@NUS Repository. https://doi.org/10.1186/1477-5956-9-3
Rights: Attribution 4.0 International
Abstract: Background: Hair bulge progenitor cells (HBPCs) are multipotent stem cells derived from the bulge region of mice vibrissal hairs. The purified HBPCs express CD34, K15 and K14 surface markers. It has been reported that HBPCs could be readily induced to transdifferentiate into adipocytes and osteocytes. However, the ability of HBPCs to transdifferentiate into cardiomyocytes has not yet been investigated.Methodology/Principal Findings: The cardiomyogenic potential of HBPCs was investigated using a small cell-permeable molecule called Cardiogenol C. We established that Cardiogenol C could induce HBPCs to express transcription factors GATA4, Nkx2.5 and Tbx5, which are early specific markers for pre-cardiomyogenic cells. In prolonged cultures, the Cardiogenol C-treated HBPCs can also express muscle proteins, cardiac-specific troponin I and sarcomeric myosin heavy chain. However, we did not observe the ability of these cells to functionally contract. Hence, we called these cells cardiomyocyte-like cells rather than cardiomyocytes. We tried to remedy this deficiency by pre-treating HBPCs with Valproic acid first before exposing them to Cardiogenol C. This pretreatment inhibited, rather than improved, the effectiveness of Cardiogenol C in reprogramming the HBPCs. We used comparative proteomics to determine how Cardiogenol C worked by identifying proteins that were differentially expressed. We identified proteins that were involved in promoting cell differentiation, cardiomyocyte development and for the normal function of striated muscles. From those differentially expressed proteins, we further propose that Cardiogenol C might exert its effect by activating the Wnt signaling pathway through the suppression of Kremen1. In addition, by up-regulating the expression of chromatin remodeling proteins, SIK1 and Smarce1 would initiate cardiac differentiation.Conclusions/Significance: In conclusion, our CD34+/K15+HBPCs could be induced to transdifferentiate into cardiomyocyte-like cells using a small molecule called Cardiogenol C. The process involves activation of the Wnt signaling pathway and altered expression of several key chromatin remodeling proteins. The finding is clinically significant as HBPCs offer a readily accessible and autologous source of progenitor cells for cell-based therapy of heart disease, which is one of major killers in developed countries. © 2011 Yau et al; licensee BioMed Central Ltd.
Source Title: Proteome Science
URI: https://scholarbank.nus.edu.sg/handle/10635/181648
ISSN: 14775956
DOI: 10.1186/1477-5956-9-3
Rights: Attribution 4.0 International
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