Forskolin and IBMX Induce Neural Transdifferentiation of MSCs Through Downregulation of the NRSF
Year: 2019
Type: article
Abstract: Neural differentiation of mesenchymal stem cells is a controversial phenomenon, as it would require transdifferentiation across the mesoderm-ectoderm barrier. However, several laboratories have observed that MSCs are able to be induced to express neural characteristics. Previously, we demonstrated that the cAMP-elevating agents, forskolin and IBMX, induced neural-like differentiation of MSCs, including expression of neural markers and increased sensitivity to neurotransmitters. However, due to the broad range of effects that forskolin and IBMX can elicit through the intracellular second messenger, cAMP, a better mechanistic understanding is required. Here, we show that neural induction by forskolin and IBMX is dependent on downregulation of expression of the master transcriptional regulator, neuron restrictive silencer factor (NRSF), and its downstream target genes. Since silencing of NRSF is known to initiate neural differentiation, it suggests that forskolin and IBMX result in transdifferentiation of MSCs into a neural lineage.
Source: Scientific Reports
Institution: Michigan State University
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,790
Awards: G1604697330, G164726066, EAGER: Biomanufacturing: CRISPR to increase the homogeneity and efficiency of stem cell differentiation, UNS: Biomolecular Engineering of siRNAs, G2487421281, CDI-Type II: Discovery of Biophysical Mechanisms Inducing Signaling and Cytotoxicity: An Experimental Approach Enabled by Cyber Tools, G3510797780, Collaborative Research: Dynamic degradation of proteins by ubiquitination provides a novel therapeutic for controlling elevated protein levels, G6490296102, G6543713385, G8966148392
OpenAlex ID: W2916983555
