Dynamic microRNA Profiles of Hepatic Differentiated Human Umbilical Cord Lining-Derived Mesenchymal Stem Cells

Cui, Lina; Zhou, Xinmin; Li, Jinge; Wang, Liuyi; Wang, Jingbo; Li, Qiang; Chu, Jindong; Zheng, Long Tai; Wu, Qiong; Han, Zheyi; Shi, Yongquan; Han, Ying; Fan, Daiming

doi:10.1371/journal.pone.0044737

Cited by 35 publications

(38 citation statements)

References 21 publications

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“…For example, the hepatic differentiation of human umbilical cord lining-derived MSCs (hUC-MSCs) and liver-derived progenitor cells (LDPCs) is regulated by miR-542-5p and miR-146a [140] . The miRNA miR-182 is involved in the differentiation of inner ear stem/progenitor cells into hair-like cells via the repression of Tbx1 [141] .…”

Section: Other Types Of Differentiationmentioning

confidence: 99%

MicroRNAs as novel regulators of stem cell fate

Choi

Hwang³

2013

WJSC

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Mounting evidence in stem cell biology has shown that microRNAs (miRNAs) play a crucial role in cell fate specification, including stem cell self-renewal, lineagespecific differentiation, and somatic cell reprogramming. These functions are tightly regulated by specific gene expression patterns that involve miRNAs and transcription factors. To maintain stem cell pluripotency, specific miRNAs suppress transcription factors that promote differentiation, whereas to initiate differentiation, lineagespecific miRNAs are upregulated via the inhibition of transcription factors that promote self-renewal. Small molecules can be used in a similar manner as natural miRNAs, and a number of natural and synthetic small molecules have been isolated and developed to regulate stem cell fate. Using miRNAs as novel regulators of stem cell fate will provide insight into stem cell biology and aid in understanding the molecular mechanisms and crosstalk between miRNAs and stem cells.Ultimately, advances in the regulation of stem cell fate will contribute to the development of effective medical therapies for tissue repair and regeneration. This review summarizes the current insights into stem cell fate determination by miRNAs with a focus on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.© 2013 Baishideng. All rights reserved. Key words:MicroRNA; Stem cell fate; Differentiation; Self-renewal; Reprogramming; Small molecule Core tip: Stem cells are important in regenerative medicine applications due to their capacity to self-renew and differentiate into specific cell types. MicroRNAs (miRNAs) are short non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Recent studies suggest that miRNAs are key molecules in the regulation of stem cell fate decisions; this regulation is manifested as the fine tuning of cell-and tissue-specific gene expression. This review summarizes the current insights into stem cell fate determination by miRNAs and focuses on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.

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Section: Other Types Of Differentiationmentioning

confidence: 99%

MicroRNAs as novel regulators of stem cell fate

Choi

Hwang³

2013

WJSC

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“…In addition, novel assays of prospective high specificity are being developed: recent data from Cui et al further highlighted the molecular mechanisms leading to hepatic differentiation of human cord-lining mesenchymal stem cells (CL-MSCs). The authors characterized the micro RNA profile of both undifferentiated and hepatocyte-differentiated cells, suggesting that 25 RNAs were overexpressed and 46 were downregulated [108].…”

Section: Hepatocyte Differentiation Protocols and Characterization Ofmentioning

confidence: 99%

Recent Advances in Derivation of Functional Hepatocytes from Placental Stem Cells

Iacono

Anzalone²,

Corrao

et al. 2013

TOTERMJ

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End-stage liver diseases are one of the leading causes of death in the world. Often orthotopic liver transplantation represents the final therapeutic choice. The limits of this approach are the scarcity of donor livers available, and the many side effects related to the administration of immune suppressants to the patients. Cellular therapy for liver diseases is increasingly being viewed as a promising strategy to provide hepatocytes to replenish the parenchymal cells of the organ. This technique suffers of some important limitations, such as the difficulty in isolating sufficient cell numbers (e.g. when adult or foetal hepatocytes are used for transplantation), the limited viability of isolated hepatocytes and, when applicable, the limited differentiation of stem cells (when hepatocyte-like cells are derived from hepatic or extra-hepatic progenitor populations).In recent years, perinatal stem cells have been proposed as reliable cellular populations which may be successfully used to derive hepatocyte-like cells. These cells feature key advantages over other adult stem cells: may be easily sourced from the tissues of origin, can be expanded ex vivo to obtain high cell numbers, may be differentiated towards hepatocyte-like cells. In addition, these cells feature relevant immunomodulatory and anti-inflammatory activities, and their sourcing is not limited by ethical concernsIn the present review we analyze the molecular basis of hepatocyte biology and development, and discuss the recent advances in deriving hapatocyte-like cells from perinatal stem cells. Very recent papers on mesenchymal stem cells derived from bone marrow and adipose tissues are also comparatively discussed as prototypes of the use of adult extrahepatic stem cells. In our opinion, perinatal stem cells do represent a promising tool for liver regenerative medicine, and recent research reports further strengthened this perception and fostered further efforts by multiple research groups worldwide.

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“…For example, miR-300 regulates differentiation of primitive cardiac progenitors [13], Dlk1-Dio3 ncRNA reduce neural differentiation potential [14]. Besides, Cui L [15] reported that many of Dlk1-Dio3 miRNAs (miR-127, miR-376a, miR-136, miR-539, miR-154) were induced during hepatic differentiation of human umbilical cord lining-derived mesenchymal stem cells. While few reports have been published on the role of Dlk1-Dio3 microRNA clusters in LPC hepatic differentiation.…”

Section: Introductionmentioning

confidence: 99%

Mir-382 Promotes Differentiation of Rat Liver Progenitor Cell WB-F344 by Targeting Ezh2

Zheng

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Liver progenitor cells (LPCs) were considered as a promising hepatocyte source of cell therapy for liver disease due to their self-renewal and differentiation capacities, while little is known about the mechanism of LPC differentiate into hepatocytes. This study aims to explore the effect of miR-382, a member of Dlk1-Dio3 microRNA cluster, during hepatic differentiation from LPCs. Methods: In this study, we used rat liver progenitor cell WB-F344 as LPC cell model and HGF as inducer to simulate the process of LPCs hepatic differentiation, then microRNAs were quantified by qPCR. Next, WB-F344 cell was transfected with miR-382 mimics, then hepatocyte cell trait was characterized by multiple experiments, including that periodic acid schiff staining and cellular uptake and excretion of indocyanine green to evaluate the hepatocellular function, qPCR and Western Blotting analysis to detect the hepatocyte-specific markers (ALB, Ttr, Apo E and AFP) and transmission electron microscopy to observe the hepatocellular morphology. Moreover, Luciferase reporter assay was used to determine whether Ezh2 is the direct target of miR-382. Results: We found that miR-382 increased gradually and was inversely correlated with the potential target, Ezh2, during WB-F344 hepatic differentiation. In addition, functional studies indicated that miR-382 increased the level of hepatocyte-specific genes. Conclusions: This study demonstrates that miR-382 may be a novel regulator of LPCs differentiation by targeting Ezh2.

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Dynamic microRNA Profiles of Hepatic Differentiated Human Umbilical Cord Lining-Derived Mesenchymal Stem Cells

Cited by 35 publications

References 21 publications

MicroRNAs as novel regulators of stem cell fate

MicroRNAs as novel regulators of stem cell fate

Recent Advances in Derivation of Functional Hepatocytes from Placental Stem Cells

Mir-382 Promotes Differentiation of Rat Liver Progenitor Cell WB-F344 by Targeting Ezh2

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