Stem cell neural differentiation: a model for chemical biology

Neural stem cell self-renewal and differentiation is orchestrated by precise control of gene expression involving nuclear receptor TLX. Let-7b, a member of the let-7 microRNA family, is expressed in mammalian brains and exhibits increased expression during neural differentiation. However, the role of let-7b in neural stem cell proliferation and differentiation remains unknown. Here we show that let-7b regulates neural stem cell proliferation and differentiation by targeting the stem cell regulator TLX and the cell cycle regulator cyclin D1. Overexpression of let-7b led to reduced neural stem cell proliferation and increased neural differentiation, whereas antisense knockdown of let-7b resulted in enhanced proliferation of neural stem cells. Moreover, in utero electroporation of let-7b to embryonic mouse brains led to reduced cell cycle progression in neural stem cells. Introducing an expression vector of Tlx or cyclin D1 that lacks the let-7b recognition site rescued let-7b-induced proliferation deficiency, suggesting that both TLX and cyclin D1 are important targets for let-7b-mediated regulation of neural stem cell proliferation. Let-7b, by targeting TLX and cyclin D1, establishes an efficient strategy to control neural stem cell proliferation and differentiation.

Download Full-text

Moringin Induces Neural Differentiation in the Stem Cell of the Human Periodontal Ligament

Scientific Reports ◽

10.1038/s41598-018-27492-0 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 11

Author(s):

Letizia Romeo ◽

Francesca Diomede ◽

Agnese Gugliandolo ◽

Domenico Scionti ◽

Fabrizio Lo Giudice ◽

...

Keyword(s):

Stem Cell ◽

Periodontal Ligament ◽

Neural Differentiation

Download Full-text

Epsins Regulate Mouse Embryonic Stem Cell Exit from Pluripotency and Neural Commitment by Controlling Notch Activation

Stem Cells International ◽

10.1155/2019/4084351 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Marina Cardano ◽

Jacopo Zasso ◽

Luca Ruggiero ◽

Giuseppina Di Giacomo ◽

Matteo Marcatili ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Embryonic Stem Cells ◽

Notch Signaling ◽

Neural Differentiation ◽

Radial Glia ◽

Embryonic Stem ◽

Mouse Embryonic Stem Cell ◽

Neural Progenitors ◽

Notch Activation

Epsins are part of the internalization machinery pivotal to control clathrin-mediated endocytosis. Here, we report that epsin family members are expressed in mouse embryonic stem cells (mESCs) and that epsin1/2 knockdown alters both mESC exits from pluripotency and their differentiation. Furthermore, we show that epsin1/2 knockdown compromises the correct polarization and division of mESC-derived neural progenitors and their conversion into expandable radial glia-like neural stem cells. Finally, we provide evidence that Notch signaling is impaired following epsin1/2 knockdown and that experimental restoration of Notch signaling rescues the epsin-mediated phenotypes. We conclude that epsins contribute to control mESC exit from pluripotency and allow their neural differentiation by appropriate modulation of Notch signaling.

Download Full-text

Neural Differentiation of Human Adipose Tissue-Derived Stem Cells Involves Activation of the Wnt5a/JNK Signalling

Stem Cells International ◽

10.1155/2015/178618 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 23

Author(s):

Sujeong Jang ◽

Jong-Seong Park ◽

Han-Seong Jeong

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Neural Differentiation ◽

Neural Induction ◽

Stem Cell Differentiation ◽

Human Adipose Tissue ◽

Pcr Analysis ◽

Rt Pcr ◽

Jnk Pathway ◽

Expression Levels

Stem cells are a powerful resource for cell-based transplantation therapies, but understanding of stem cell differentiation at the molecular level is not clear yet. We hypothesized that the Wnt pathway controls stem cell maintenance and neural differentiation. We have characterized the transcriptional expression of Wnt during the neural differentiation of hADSCs. After neural induction, the expressions of Wnt2, Wnt4, and Wnt11 were decreased, but the expression of Wnt5a was increased compared with primary hADSCs in RT-PCR analysis. In addition, the expression levels of most Fzds and LRP5/6 ligand were decreased, but not Fzd3 and Fzd5. Furthermore, Dvl1 and RYK expression levels were downregulated in NI-hADSCs. There were no changes in the expression of ß-catenin and GSK3ß. Interestingly, Wnt5a expression was highly increased in NI-hADSCs by real time RT-PCR analysis and western blot. Wnt5a level was upregulated after neural differentiation and Wnt3, Dvl2, and Naked1 levels were downregulated. Finally, we found that the JNK expression was increased after neural induction and ERK level was decreased. Thus, this study shows for the first time how a single Wnt5a ligand can activate the neural differentiation pathway through the activation of Wnt5a/JNK pathway by binding Fzd3 and Fzd5 and directing Axin/GSK-3ß in hADSCs.

Download Full-text