From stem cells to neural networks: recent advances and perspectives for neurodevelopmental disorders

Gaspard, Nicolas; Vanderhaeghen, Pierre

doi:10.1111/j.1469-8749.2010.03827.x

Cited by 52 publications

(37 citation statements)

References 48 publications

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“…Consequently, we sought to improve the telencephalic induction in our differentiation paradigm. An organized cross-regulation of Shh and Wnt signaling is required for normal forebrain development, whereby Wnts are strongly expressed in the dorsal and caudal domains of the developing central nervous system (CNS) (Gaspard and Vanderhaeghen, 2011;Houart et al, 2002;Ohkubo et al, 2002;Shimogori et al, 2004;Hébert and Fishell, 2008) (schematized in Fig. 1A,Aa).…”

Section: Efficient Telencephalic Patterning In Mescsmentioning

confidence: 99%

Duration of culture and sonic hedgehog signaling differentially specify PV versus SST cortical interneuron fates from embryonic stem cells

et al. 2015

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Medial ganglionic eminence (MGE)-derived GABAergic cortical interneurons (cINs) consist of multiple subtypes that are involved in many cortical functions. They also have a remarkable capacity to migrate, survive and integrate into cortical circuitry after transplantation into postnatal cortex. These features have engendered considerable interest in generating distinct subgroups of interneurons from pluripotent stem cells (PSCs) for the study of interneuron fate and function, and for the development of cell-based therapies. Although advances have been made, the capacity to generate highly enriched pools of subgroup fatecommitted interneuron progenitors from PSCs has remained elusive. Previous studies have suggested that the two main MGE-derived interneuron subgroups -those expressing somatostatin (SST) and those expressing parvalbumin (PV) -are specified in the MGE from Nkx2.1-expressing progenitors at higher or lower levels of sonic hedgehog (Shh) signaling, respectively. To further explore the role of Shh and other factors in cIN fate determination, we generated a reporter line such that Nkx2.1-expressing progenitors express mCherry and postmitotic Lhx6-expressing MGE-derived interneurons express GFP. Manipulations of Shh exposure and time in culture influenced the subgroup fates of ESC-derived interneurons. Exposure to higher Shh levels, and collecting GFP-expressing precursors at 12 days in culture, resulted in the strongest enrichment for SST interneurons over those expressing PV, whereas the strongest enrichment for PV interneurons was produced by lower Shh and by collecting mCherry-expressing cells after 17 days in culture. These findings confirm that fate determination of cIN subgroups is crucially influenced by Shh signaling, and provide a system for the further study of interneuron fate and function.

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Section: Efficient Telencephalic Patterning In Mescsmentioning

confidence: 99%

Duration of culture and sonic hedgehog signaling differentially specify PV versus SST cortical interneuron fates from embryonic stem cells

et al. 2015

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“…To evaluate the influence of cell sources and growth factors included in the culture medium, we analyzed the expression of 106 pluripotent and neuronal marker genes (Supporting Information Table S3) [44][45][46][47][48] in diNSC-derived neurospheres established using the various culture conditions shown in Figure 5D, by hierarchical clustering. In this analysis, the MEF-derived neurospheres constituted one group, and the two adult fibroblast-derived neurospheres were clustered separately.…”

Section: Microarray Analysis Of Dinsc-derived Neurospheresmentioning

confidence: 99%

Neural Stem Cells Directly Differentiated from Partially Reprogrammed Fibroblasts Rapidly Acquire Gliogenic Competency

et al. 2012

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Neural stem cells (NSCs) were directly induced from mouse fibroblasts using four reprogramming factors (Oct4, Sox2, Klf4, and cMyc) without the clonal isolation of induced pluripotent stem cells (iPSCs). These NSCs gave rise to both neurons and glial cells even at early passages, while early NSCs derived from clonal embryonic stem cells (ESCs)/ iPSCs differentiated mainly into neurons. Epidermal growth factor-dependent neurosphere cultivation efficiently propagated these gliogenic NSCs and eliminated residual pluripotent cells that could form teratomas in vivo. We concluded that these directly induced NSCs were derived from partially reprogrammed cells, because dissociated ESCs/ iPSCs did not form neurospheres in this culture condition. These NSCs differentiated into both neurons and glial cells in vivo after being transplanted intracranially into mouse striatum. NSCs could also be directly induced from adult human fibroblasts. The direct differentiation of partially reprogrammed cells may be useful for rapidly preparing NSCs with a strongly reduced propensity for tumorigenesis.

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“…A wide range of different strategies is under investigation for PD treatment, with a major focus research on stem cell therapy applications. Exogenous molecules are known to guide neural differentiation and are responsible for the high grade of phenotype specification, including induction of axonal growth and establishment of synaptic contact [73]. Milosevic et al [74] detected P2Y4, P2Y6, and P2X4 receptor expression in cultured human NPCs from human fetal midbrain.…”

Section: Parkinson's Diseasementioning

confidence: 99%

Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration

Glaser

Cappellari

Pillat

et al. 2011

Purinergic Signalling

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Replacement of lost or dysfunctional tissues by stem cells has recently raised many investigations on therapeutic applications. Purinergic signaling has been shown to regulate proliferation, differentiation, cell death, and successful engraftment of stem cells originated from diverse origins. Adenosine triphosphate release occurs in a controlled way by exocytosis, transporters, and lysosomes or in large amounts from damaged cells, which is then subsequently degraded into adenosine. Paracrine and autocrine mechanisms induced by immune responses present critical factors for the success of stem cell therapy. While P1 receptors generally exert beneficial effects including anti-inflammatory activity, P2 receptor-mediated actions depend on the subtype of stimulated receptors and localization of tissue repair. Pro-inflammatory actions and excitatory tissue damages mainly result from P2X7 receptor activation, while other purinergic receptor subtypes participate in proliferation and differentiation, thereby providing adequate niches for stem cell engraftment and novel mechanisms for cell therapy and endogenous tissue repair. Therapeutic applications based on regulation of purinergic signaling are foreseen for kidney and heart muscle regeneration, Clara-like cell replacement for pulmonary and bronchial epithelial cells as well as for induction of neurogenesis in case of neurodegenerative diseases.

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From stem cells to neural networks: recent advances and perspectives for neurodevelopmental disorders

Cited by 52 publications

References 48 publications

Duration of culture and sonic hedgehog signaling differentially specify PV versus SST cortical interneuron fates from embryonic stem cells

Duration of culture and sonic hedgehog signaling differentially specify PV versus SST cortical interneuron fates from embryonic stem cells

Neural Stem Cells Directly Differentiated from Partially Reprogrammed Fibroblasts Rapidly Acquire Gliogenic Competency

Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration

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