0000000000237499
AUTHOR
Susan Gascon
Oligodendrogliogenic and neurogenic adult subependymal zone neural stem cells constitute distinct lineages and exhibit differential responsiveness to Wnt signalling.
The adult mouse subependymal zone (SEZ) harbours adult neural stem cells (aNSCs) that give rise to neuronal and oligodendroglial progeny. However it is not known whether the same aNSC can give rise to neuronal and oligodendroglial progeny or whether these distinct progenies constitute entirely separate lineages. Continuous live imaging and single-cell tracking of aNSCs and their progeny isolated from the mouse SEZ revealed that aNSCs exclusively generate oligodendroglia or neurons, but never both within a single lineage. Moreover, activation of canonical Wnt signalling selectively stimulated proliferation within the oligodendrogliogenic lineage, resulting in a massive increase in oligodendr…
Reprogramming of Pericyte-Derived Cells of the Adult Human Brain into Induced Neuronal Cells
SummaryReprogramming of somatic cells into neurons provides a new approach toward cell-based therapy of neurodegenerative diseases. A major challenge for the translation of neuronal reprogramming into therapy is whether the adult human brain contains cell populations amenable to direct somatic cell conversion. Here we show that cells from the adult human cerebral cortex expressing pericyte hallmarks can be reprogrammed into neuronal cells by retrovirus-mediated coexpression of the transcription factors Sox2 and Mash1. These induced neuronal cells acquire the ability of repetitive action potential firing and serve as synaptic targets for other neurons, indicating their capability of integrat…
Sox2-Mediated Conversion of NG2 Glia into Induced Neurons in the Injured Adult Cerebral Cortex
Summary The adult cerebral cortex lacks the capacity to replace degenerated neurons following traumatic injury. Conversion of nonneuronal cells into induced neurons has been proposed as an innovative strategy toward brain repair. Here, we show that retrovirus-mediated expression of the transcription factors Sox2 and Ascl1, but strikingly also Sox2 alone, can induce the conversion of genetically fate-mapped NG2 glia into induced doublecortin (DCX)+ neurons in the adult mouse cerebral cortex following stab wound injury in vivo. In contrast, lentiviral expression of Sox2 in the unlesioned cortex failed to convert oligodendroglial and astroglial cells into DCX+ cells. Neurons induced following …
Search forBs0→μ+μ−andB0→μ+μ−Decays with CDF II
A search has been performed for B{sub s}{sup 0} {yields} {mu}{sup +}{mu}{sup -} and B{sup 0} {yields} {mu}{sup +}{mu}{sup -} decays using 7 fb{sup -1} of integrated luminosity collected by the CDF II detector at the Fermilab Tevatron collider. The observed number of B{sup 0} candidates is consistent with background-only expectations and yields an upper limit on the branching fraction of {Beta}(B{sup 0} {yields} {mu}{sup +}{mu}{sup -}) < 6.0 x 10{sup -9} at 95% confidence level. We observe an excess of B{sub s}{sup 0} candidates. The probability that the background processes alone could produce such an excess or larger is 0.27%. The probability that the combination of background and the expe…
Neuronal LRP4 regulates synapse formation in the developing CNS
The low-density lipoprotein receptor-related protein 4 (LRP4) is essential in muscle fibers for the establishment of the neuromuscular junction. Here, we show that LRP4 is also expressed by embryonic cortical and hippocampal neurons, and that downregulation of LRP4 in these neurons causes a reduction in density of synapses and number of primary dendrites. Accordingly, overexpression of LRP4 in cultured neurons had the opposite effect inducing more but shorter primary dendrites with an increased number of spines. Transsynaptic tracing mediated by rabies virus revealed a reduced number of neurons presynaptic to the cortical neurons in which LRP4 was knocked down. Moreover, neuron-specific kno…
Programming of neural progenitors of the adult subependymal zone towards a glutamatergic identity by Neurogenin2
ABSTRACTWhile the adult subependymal zone (SEZ) harbors pools of distinct neural stem cells that generate different types of GABAergic interneurons, a small progenitor population in the dorsal SEZ expresses Neurog2 and gives rise to glutamatergic neurons. Here we investigated whether SEZ progenitors can be programmed towards glutamatergic neurogenesis through forced expression of Neurog2. Retrovirus-mediated expression of Neurog2 induced the glutamatergic neuron lineage markers Tbr2 and Tbr1 in cultured SEZ progenitors which subsequently differentiated into functional glutamatergic neurons. Likewise, retrovirus-mediated expression of Neurog2 in dividing SEZ progenitors within the adult SEZ …
Observation of the rare B(s)(0) + decay from the combined analysis of CMS and LHCb data.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported licence.-- et al.
Identification and Successful Negotiation of a Metabolic Checkpoint in Direct Neuronal Reprogramming
Despite the widespread interest in direct neuronal reprogramming, the mechanisms underpinning fate conversion remain largely unknown. Our study revealed a critical time point after which cells either successfully convert into neurons or succumb to cell death. Co-transduction with Bcl-2 greatly improved negotiation of this critical point by faster neuronal differentiation. Surprisingly, mutants with reduced or no affinity for Bax demonstrated that Bcl-2 exerts this effect by an apoptosis-independent mechanism. Consistent with a caspase-independent role, ferroptosis inhibitors potently increased neuronal reprogramming by inhibiting lipid peroxidation occurring during fate conversion. Genome-w…