Researchers from the Neural Stem Cell Institute have discovered that the secreted protein NPTX1 plays a key role in neural lineage specification. They found that NPTX1 is rapidly upregulated during neural induction from human pluripotent stem cells (hPSCs) and that by contolling its expression levels it is possible to reduce or initiate neural lineage commitment.
There are different protocols to generate neurons ad neural progenitor cells form human pluripotent stem cells. However, not much is known about the gene expression profiles of the differentiation neurons. In this paper, Chen J et al, have generated induced pluripotent stem cells from both fibroblasts and dental pulp stem cells, and used RNA-sequencing to reveal the gene expression profiles of the stem cells-derived neuron precursor cells (NPCs) and neurons.
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Abstract: Since their discovery twenty years ago and prospective isolation a decade later, neural stem cells (NSCs), their progenitors, and differentiated cell derivatives along with other stem-cell based strategies have advanced steadily toward clinical trials, spurred by the immense need to find reparative therapeutics for central nervous system (CNS) diseases and injury. Current phase I/II trials using stem cells in the CNS are the vanguard for the widely anticipated next generation of regenerative therapies and as such are pioneering the stem cell therapy process. While translation has typically been the purview of industry, academic researchers are increasingly driven to bring their findings toward treatments and face challenges in knowledge gap and resource access that are accentuated by the unique financial, manufacturing, scientific, and regulatory aspects of cell therapy. Solutions are envisioned that both address the significant unmet medical need and lead to increased funding for basic and translational research.
Jacob Blumenthal's insight:
I discovered this paper in a LinkedIn profile of one of my new contacts... Although it was published in 2011, it gives a short overview on the available sources for neural stem cells (NSCs), and on their therapeutic potential in central nervous system (CNS)-related pathologies.
A new study examining the brains of fruit flies reveals a novel stem cell mechanism that may help explain how neurons form in humans.
Jacob Blumenthal's insight:
Abstract: "Human outer subventricular zone (OSVZ) neural progenitors and Drosophila type II neuroblasts both generate intermediate neural progenitors (INPs) that populate the adult cerebral cortex or central complex, respectively. It is unknown whether INPs simply expand or also diversify neural cell types. Here we show that Drosophila INPs sequentially generate distinct neural subtypes, that INPs sequentially express Dichaete, Grainy head and Eyeless transcription factors, and that these transcription factors are required for the production of distinct neural subtypes. Moreover, parental type II neuroblasts also sequentially express transcription factors and generate different neuronal/glial progeny over time, providing a second temporal identity axis. We conclude that neuroblast and INP temporal patterning axes act together to generate increased neural diversity within the adult central complex; OSVZ progenitors may use similar mechanisms to increase neural diversity in the human brain".
Fred Gage and Sally Temple published a very interesting review about neural stem cells (NSCs) in Neuron journal. This is an open-access, and highly recommended review from one of the leading scientist in the field.
Since the discovery of direct reprogramming by Marius Wernig, few years ago, it is posiible to directly differentiate fibroblasts into neuronal cells In order to study neuronal-related disease phenotypes. In this paper, from the group of Thomas Sudhof, fibroblasts, taken from an autism mouse model ,that harbors a mutation in the neuroligin gene, are directly differentiate into neuronal cells. The researchers found that these cells now exhibit a phenotype similar to that observed in the endogenous neurons of the mouse model.
Researchers from Lund University have developed a method to induce cell reprogramming in-vivo. They designed reprogramming genes that could be activated or deactivated using the drug doxycycline. They inserted these genes into fibroblasts in the laboratory and then injected these cells into living rats. Then they put the activating drug through in the animals’ drinking water.The result was reprogramming of the fibroblasts into neurons inside the brain.
The authors demonstrate the highly efficient derivation of human cortical interneurons using an NKX2.1::GFP human embryonic stem cell reporter line. This study lays the foundation for studying cortical interneurons involvement in human disease pathology.
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