Enhancing the efficiency of direct reprogramming of human mesenchymal stem cells into mature neuronal-like cells with the combination of small molecule modulators of chromatin modifying enzymes, SMAD signaling and cyclic adenosine monophosphate levels

Alexanian, Arshak R.; Liu, Qingsong; Zhang, Zhiying

doi:10.1016/j.biocel.2013.04.022

Cited by 23 publications

(18 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The fate of HSCs is regulated by small molecules that promote self-renewal [181][182][183] . Using small molecules, multipotent MSCs can differentiate into various non-hematopoietic cells, such as chondrocytes [134,184] , osteoblasts [185,186] , hepatocytes [187] , cardiomyocytes [188,189] , adipocytes [190,191] and neuronal-like cells [192][193][194] . Additionally, the maintenance of MSCs is associated with the Wnt signaling pathway [195,196] .…”

Section: Small Molecules and Stem Cell Fatementioning

confidence: 99%

MicroRNAs as novel regulators of stem cell fate

Choi

Hwang³

2013

WJSC

View full text Add to dashboard Cite

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.

show abstract

Section: Small Molecules and Stem Cell Fatementioning

confidence: 99%

MicroRNAs as novel regulators of stem cell fate

Choi

Hwang³

2013

WJSC

View full text Add to dashboard Cite

show abstract

“…After 2 to 3 weeks, about 95% of the cells expressed markers for neural progenitors and mature neurons. The induced neuron-like cells were also shown to form synapse-like structures when co-cultured with human neural stem cells [10]. The MSC-derived neuron like cells induced by dorsomorphin and SB431542-containing small molecule cocktail also exhibited dopaminergic neuronal properties as revealed by an increase in dopamine release [12].…”

Section: Small Molecules Facilitate Direct Reprogramming Into Neuronsmentioning

confidence: 85%

“…Dorsomorphin and SB431542 were chosen for this study because of their inhibitory effects on SMAD signaling [10]. Simultaneous inhibition of both the activin/nodal and BMP pathways is accomplished through the use of dorsomorphin and SB431542.…”

Section: Small Molecules Facilitate Direct Reprogramming Into Neuronsmentioning

confidence: 99%

“…Direct reprogramming of human mesenchymal stem cells (MSCs) into neuron-like cells has been achieved by introducing dorsomorphin and SB431542 into a previously described neuronal induction cocktail containing epigenetic and cAMP modifiers, including Trichostatin A (TSA), RG-108, 8-BrcAMP, and Rolipram [10,11]. Dorsomorphin and SB431542 were chosen for this study because of their inhibitory effects on SMAD signaling [10].…”

Section: Small Molecules Facilitate Direct Reprogramming Into Neuronsmentioning

confidence: 99%

See 1 more Smart Citation

Direct Reprogramming Facilitated by Small Molecules

Lewis¹,

Brewster²,

Tian³

et al. 2015

J Stem Trans Bio

View full text Add to dashboard Cite

The ability to reprogram cellular fate provide great hope for regenerative medicine and offer excellent cellular resources for disease modeling and drug discovery. Direct reprogramming, also called lineage reprogramming or transdifferentiation, is the process of changing one cell type to another without going through an intermediate pluripotent step. Direct reprogramming is generally achieved using lineage-specific transcription factors or microRNAs. The efficiency of direct reprogramming is usually relatively low without the aid of small molecule compounds. By using small molecules in conjunction with transcription factors or microRNAs, the efficiency of direct reprogramming is greatly increased and sometimes even less transgenes are required. Common targets of the small molecules used in direct reprogramming include epigenetic regulators, such as DNA methyltransferases and histone deacetylases, and signaling molecules, such as GSK3β and TGFβ pathways. By modulating epigenetic landscape and signaling pathways critical for cell fate determination, these small molecules allow cell fate conversion in a rapid and efficient manner. This review aims to highlight the versatile roles of small molecules in direct reprogramming.

show abstract

“…Forskolin along with GDNF and embryonic midbrain morphogens were also used for neuronal induction of human exfoliated deciduous teeth (SHED) to differentiate to dopaminergic neurons [173]. Alexanian et al [174] used the combination of small molecules that affect the regulation of chromatin structure and function and agents that favor neural differentiation to generate neural-like cells from human MSCs. The efficiency of neuronal differentiation and maturation was improved by two specific inhibitors of SMAD signaling (SMAD1/3 and SMAD3/5/8) that play an important role in neuronal differentiation of ESCs and were added to chromatin-modifying enzymes.…”

Section: Neuronal Differentiation Using Extrinsic Cuesmentioning

confidence: 99%