Browsing by Author "Ho, Jennifer H."

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DNA Methyltransferases Modulate Hepatogenic Lineage Plasticity of Mesenchymal Stromal Cells
(2017-07-11)
Lee, Chien-Wei
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Huang, Wei-Chih
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Huang, Hsien-Da
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Huang, Yi-Hsiang
;
Ho, Jennifer H.
The irreversibility of developmental processes in mammalian cells has been challenged by rising evidence that de-differentiation of hepatocytes occurs in adult liver. However, whether reversibility exists in mesenchymal stromal cell (MSC)-derived hepatocytes (dHeps) remains elusive. In this study, we find that hepatogenic differentiation (HD) of MSCs is a reversible process and is modulated by DNA methyltransferases (DNMTs). DNMTs are regulated by transforming growth factor beta 1 (TGF beta 1), which in turn controls hepatogenic differentiation and de-differentiation. In addition, a stepwise reduction in TGF beta 1 concentrations in culture media increases DNMT1 and decreases DNMT3 in primary hepatocytes (Heps) and confers Heps with multi-differentiation potentials similarly to MSCs. Hepatic lineage reversibility of MSCs and lineage conversion of Heps are regulated byDNMTs in response to TGF gamma 1. This previously unrecognized TGF beta 1-DNMTs-MSC-HD axis may further increase the understanding the normal and pathological processes in the liver, as well as functions of MSCs after transplantation to treat liver diseases.
The effects of actin cytoskeleton perturbation on keratin intermediate filament formation in mesenChymal stem/stromal cells
(2014-04-01)
Chang, Tzu-Hao
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Huang, Hsien-Da
;
Ong, Wei-Kee
;
Fu, Yun-Ju
;
Lee, Oscar K.
F-actin plays a crucial role in composing the three-dimensional cytoskeleton and F-actin depolymerization alters fate choice of mesenchymal stem/stromal cells (MSCs). Here, we investigated differential gene expression and subsequent physiological changes in response to F-actin perturbation by latrunculin B in MSCs. Nineteen genes were down-regulated and 27 genes were up-regulated in the first 15 min after F-actin depolymerization. Functional enrichment analysis revealed that five genes involved in keratin (KRT) intermediate filaments clustering in the chromosome 17q21.2 region, i.e., KRT14, KRT19, KRT34, KRT-associated protein (KRTAP) 1-5, and KRTAP2-3, were strongly up-regulated. Transcription factor prediction identified NKX2.5 as the potential transcription factor to control KRT19, KRT34, KRTAP1-5, and KRTAP2-3; and indeed, the protein level of NKX2.5 was markedly increased in the nuclear fraction within 15 min of F-actin depolymerization. The peak of keratin intermediate filament formation was 1 h after actin perturbation, and the morphological changes showed by decrease in the ratio of long-axis to shortaxis diameter in MSCs was observed after 4 h. Together, F-actin depolymerization rapidly triggers keratin intermediate filament formation by turning on keratin-related genes on chromosome 17q21.2. Such findings offer new insight in lineage commitment of MSCs and further scaffold design in MSC-based tissue engineering. (C) 2014 Elsevier Ltd. All rights reserved.