Wenying Wang, Jiangjing Li, Xiajing Zhang, Shuang Wang, Heming Zhang, Changjun Gao, Xude Sun
Objective To investigate the alterations in hippocampus neuron morphology, the expression of neurogenin 2 (Ngn2) and methyl-CpG-binding protein 2 (MeCP2) in hippocampus after electromagnetic pulse (EMP) irradiation. Methods Adult healthy male SD rats were randomly divided into control group, EMP 7-day group, and EMP 14-day group (n=12). Hippocampus neuron morphology was tested by HE staining; the expression of Ngn2 and MeCP2 were measured by Western blotting and fluorescent immunohistochemistry; the protein levels of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95) were measured by Western blotting...
May 2020: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Simone Mesman, Marten P Smidt
The mesodiencephalic dopaminergic (mdDA) group of neurons comprises molecularly distinct subgroups, of which the substantia nigra (SN) and ventral tegmental area (VTA) are the best known, due to the selective degeneration of the SN during Parkinson's disease. However, although significant research has been conducted on the molecular build-up of these subsets, much is still unknown about how these subsets develop and which factors are involved in this process. In this review, we aim to describe the life of an mdDA neuron, from specification in the floor plate to differentiation into the different subsets...
June 30, 2020: International Journal of Molecular Sciences
Filip Rosa, Ashutosh Dhingra, Betül Uysal, G Dulini C Mendis, Heidi Loeffler, Gina Elsen, Stephan Mueller, Niklas Schwarz, Melissa Castillo-Lizardo, Claire Cuddy, Felicitas Becker, Peter Heutink, Christopher A Reid, Steven Petrou, Holger Lerche, Snezana Maljevic
Neurons differentiated from induced pluripotent stem cells (iPSCs) typically show regular spiking and synaptic activity but lack more complex network activity critical for brain development, such as periodic depolarizations including simultaneous involvement of glutamatergic and GABAergic neurotransmission. We generated human iPSC-derived neurons exhibiting spontaneous oscillatory activity after cultivation of up to 6 months, which resembles early oscillations observed in rodent neurons. This behavior was found in neurons generated using a more "native" embryoid body protocol, in contrast to a "fast" protocol based on NGN2 overexpression...
June 9, 2020: Stem Cell Reports
Mitsuru Ishikawa, Takeshi Aoyama, Shoichiro Shibata, Takefumi Sone, Hiroyuki Miyoshi, Hirotaka Watanabe, Mari Nakamura, Saori Morota, Hiroyuki Uchino, Andrew S Yoo, Hideyuki Okano
Obtaining differentiated cells with high physiological functions by an efficient, but simple and rapid differentiation method is crucial for modeling neuronal diseases in vitro using human pluripotent stem cells (hPSCs). Currently, methods involving the transient expression of one or a couple of transcription factors have been established as techniques for inducing neuronal differentiation in a rapid, single step. It has also been reported that microRNAs can function as reprogramming effectors for directly reprogramming human dermal fibroblasts to neurons...
February 25, 2020: Cells
Natalie Barretto, Hanwen Zhang, Samuel K Powell, Michael B Fernando, Siwei Zhang, Erin K Flaherty, Seok-Man Ho, Paul A Slesinger, Jubao Duan, Kristen J Brennand
BACKGROUND: Somatic cell reprogramming is routinely used to generate donor-specific human induced pluripotent stem cells (hiPSCs) to facilitate studies of disease in a human context. The directed differentiation of hiPSCs can generate large quantities of patient-derived cells; however, such methodologies frequently yield heterogeneous populations of neurons and glia that require extended timelines to achieve electrophysiological maturity. More recently, transcription factor-based induction protocols have been show to rapidly generate defined neuronal populations from hiPSCs...
February 14, 2020: Journal of Neuroscience Methods
Majid Keshavarzi, Mohammad Javad Khoshnoud, Ali Ghaffarian Bahraman, Afshin Mohammadi-Bardbori
Neurogenesis is a dynamic and physiologic developmental process that affects learning and hippocampal dependent memory. It is regulated by multi-cellular micro-environment and different types of transcription factors. The neurogenesis effects of endogenously activated aryl hydrocarbon receptor (AHR) by its endogenous ligand, 6-formylindolo[3,2-b] carbazole (FICZ), and its interactions with the Wnt/β-catenin signaling pathway were the main purpose of this study. In accordance, learning and hippocampus-dependent memory were examined...
February 10, 2020: Journal of Molecular Neuroscience: MN
Alec R Nickolls, Michelle M Lee, David F Espinoza, Marcin Szczot, Ruby M Lam, Qi Wang, Jeanette Beers, Jizhong Zou, Minh Q Nguyen, Hans J Solinski, Aisha A AlJanahi, Kory R Johnson, Michael E Ward, Alexander T Chesler, Carsten G Bönnemann
Efficient and homogeneous in vitro generation of peripheral sensory neurons may provide a framework for novel drug screening platforms and disease models of touch and pain. We discover that, by overexpressing NGN2 and BRN3A, human pluripotent stem cells can be transcriptionally programmed to differentiate into a surprisingly uniform culture of cold- and mechano-sensing neurons. Although such a neuronal subtype is not found in mice, we identify molecular evidence for its existence in human sensory ganglia. Combining NGN2 and BRN3A programming with neural crest patterning, we produce two additional populations of sensory neurons, including a specialized touch receptor neuron subtype...
January 21, 2020: Cell Reports
Andrei Gresita, Daniela Glavan, Ion Udristoiu, Bogdan Catalin, Dirk M Hermann, Aurel Popa-Wagner
After cerebral ischemia, the ratio between astroglial cells and neurons in the neurovascular unit is disrupted in the perilesional area. We hypothesized that restoring the balance within the neurovascular unit may lead to an improved neurorestoration after focal ischemia. Recently, an innovative technology has been invented to efficiently convert proliferating astroglial cells into neurons in the injured young brain. However, the conversion efficacy of this technology has not been explored in the post-stroke brains of the aged rodents...
2019: Frontiers in Aging Neuroscience
Rajasekaran Subbarayan, Rajamani Barathidasan, Selvaraj T K Raja, Gnanamani Arumugam, Sarah Kuruvilla, Palanivelu Shanthi, Suresh Ranga Rao
Spinal cord injury induces scar formation causes axonal damage that leads to the degeneration of axonal function. Still, there is no robust conceptual design to regenerate the damaged axon after spinal injury. Therefore, the present study demonstrates that human gingival derived neuronal stem cells (GNSCs) transplants in the injectable caffeic acid bioconjugated hydrogel (CBGH) helps to bridge the cavity and promote the engraftment and repopulation of transplants in the injured spinal tissue. Our study reports that the bioluminescence imaging in vivo imaging system (IVIS) provides a satisfactory progression in CBGH-GNSCs transplants compare to lesion control and CBGH alone...
October 23, 2019: Journal of Cellular Biochemistry
Kellen D Winden, Maria Sundberg, Cindy Yang, Syed M A Wafa, Sean Dwyer, Pin-Fang Chen, Elizabeth D Buttermore, Mustafa Sahin
Tuberous Sclerosis Complex (TSC) is a genetic disorder caused by mutations in TSC1 or TSC2 , and patients frequently have epilepsy, autism spectrum disorder, and/or intellectual disability, as well as other systemic manifestations. In this study, we differentiated human induced pluripotent stem cells (iPSCs) from a female patient with TSC with one or two mutations in TSC2 into neurons using induced expression of NGN2 to examine neuronal dysregulation associated with the neurological symptoms in TSC. Using this method, neuronal differentiation was comparable between the three genotypes of iPSCs...
October 7, 2019: Journal of Neuroscience
Xiu Sun, Zijian Tan, Xiao Huang, Xueyan Cheng, Yimin Yuan, Shangyao Qin, Dan Wang, Xin Hu, Yakun Gu, Wen-Jing Qian, Zhongfeng Wang, Cheng He, Zhida Su
Direct conversion of readily available non-neural cells from patients into induced neurons holds great promise for neurological disease modeling and cell-based therapy. Olfactory ensheathing cells (OECs) is a unique population of glia in olfactory nervous system. Based on the regeneration-promoting properties and the relative clinical accessibility, OECs are attracting increasing attention from neuroscientists as potential therapeutic agents for use in neural repair. Here, we report that OECs can be directly, rapidly and efficiently reprogrammed into neuronal cells by the single transcription factor Neurogenin 2 (NGN2)...
September 9, 2019: Cell Death & Disease
Nicola Mattugini, Riccardo Bocchi, Volker Scheuss, Gianluca Luigi Russo, Olof Torper, Chu Lan Lao, Magdalena Götz
Astrocytes are particularly promising candidates for reprogramming into neurons, as they maintain some of the original patterning information from their radial glial ancestors. However, to which extent the position of astrocytes influences the fate of reprogrammed neurons remains unknown. To elucidate this, we performed stab wound injury covering an entire neocortical column, including the gray matter (GM) and white matter (WM), and targeted local reactive astrocytes via injecting FLEx switch (Cre-On) adeno-associated viral (AAV) vectors into mGFAP-Cre mice...
August 21, 2019: Neuron
Fuqing Wang, Lihua Cui, Meng Qiao, Jian Ding
No abstract text is available yet for this article.
July 25, 2019: Panminerva Medica
Yichen Li, Justin K Ichida
Direct lineage conversion offers a fast and simple method to study mature neurons in vitro, but its utility for investigating neurodevelopment has remained unclear. In this issue of Cell Stem Cell, Chanda et al. (2019) use Ngn2-induced neurons to elucidate the pathogenic mechanisms of the teratogenic compound valproic acid.
July 3, 2019: Cell Stem Cell
Jan-Eric Ahlfors, Ashkan Azimi, Rouwayda El-Ayoubi, Alexander Velumian, Ilan Vonderwalde, Cecile Boscher, Oana Mihai, Sarathi Mani, Marina Samoilova, Mohamad Khazaei, Michael G Fehlings, Cindi M Morshead
BACKGROUND: Cell reprogramming is a promising avenue for cell-based therapies as it allows for the generation of multipotent, unipotent, or mature somatic cells without going through a pluripotent state. While the use of autologous cells is considered ideal, key challenges for their clinical translation include the ability to reproducibly generate sufficient quantities of cells within a therapeutically relevant time window. METHODS: We performed transfection of three distinct human somatic starting populations of cells with a non-integrating synthetic plasmid expressing Musashi 1 (MSI1), Neurogenin 2 (NGN2), and Methyl-CpG-Binding Domain 2 (MBD2)...
June 13, 2019: Stem Cell Research & Therapy
Pampa Saha, Rajaneesh Kumar Gupta, Tanusree Sen, Nilkantha Sen
An enduring deficit in neurogenesis largely contributes to the development of severe posttraumatic psychiatric disorders such as anxiety, depression, and memory impairment following Traumatic brain injury (TBI); however, the mechanism remains obscure. Here we have shown that an imbalance in the generation of GABAergic and glutamatergic neurons due to aberrant induction of vGlut1 positive glutamatergic cells is responsible for impaired neuronal differentiation in the hippocampus following TBI. To elucidate the molecular mechanism, we found that TBI activates a transcription factor Pax3 by increasing its acetylation status and subsequently induces Ngn2 transcription...
June 6, 2019: Journal of Neurotrauma
Zhonghai Huang, Jing Liu, Jingyu Jin, Qingpei Chen, Lisa B E Shields, Yi-Ping Zhang, Christopher B Shields, Libing Zhou, Bing Zhou, Panpan Yu
Manipulation of developmentally regulated genes presents a promising strategy to enhance the intrinsic growth capability of adult neurons. Inhibitor of DNA binding 2 (Id2), a negative regulator of bHLH transcriptional factors, promotes axonal growth after its forced expression in post-mitotic neurons. Neurogenin2 (Ngn2) is a neural specific bHLH factor which controls neuronal fate and drives neuronal differentiation during development. In this study, we investigated the mechanism of Id2 in promoting axonal growth and revealed that Ngn2 contributed to the growth-activating role of Id2 in neurons...
May 27, 2019: Experimental Neurology
Maria G Garone, Valeria de Turris, Alessandro Soloperto, Carlo Brighi, Riccardo De Santis, Francesca Pagani, Silvia Di Angelantonio, Alessandro Rosa
We describe here a method to obtain functional spinal and cranial motor neurons from human induced pluripotent stem cells (iPSCs). Direct conversion into motor neuron is obtained by ectopic expression of alternative modules of transcription factors, namely Ngn2, Isl1 and Lhx3 (NIL) or Ngn2, Isl1 and Phox2a (NIP). NIL and NIP specify, respectively, spinal and cranial motor neuron identity. Our protocol starts with the generation of modified iPSC lines in which NIL or NIP are stably integrated in the genome via a piggyBac transposon vector...
May 1, 2019: Journal of Visualized Experiments: JoVE
Joseph Herdy, Simon Schafer, Yongsung Kim, Zoya Ansari, Dina Zangwill, Manching Ku, Apua Paquola, Hyungjun Lee, Jerome Mertens, Fred H Gage
Direct conversion of human somatic fibroblasts into induced neurons (iNs) allows for the generation of functional neurons while bypassing any stem cell intermediary stages. Although iN technology has an enormous potential for modeling age-related diseases, as well as therapeutic approaches, the technology faces limitations due to variable conversion efficiencies and a lack of thorough understanding of the signaling pathways directing iN conversion. Here, we introduce a new all-in-one inducible lentiviral system that simplifies fibroblast transgenesis for the two pioneer transcription factors, Ngn2 and Ascl1, and markedly improves iN yields...
May 17, 2019: ELife
Shuhui Sun, Xiao-Jing Zhu, Hao Huang, Wei Guo, Tao Tang, Binghua Xie, Xiaofeng Xu, Zunyi Zhang, Ying Shen, Zhong-Min Dai, Mengsheng Qiu
Neural progenitor cells (NPCs) are sequentially specified into neurons and glia during the development of central nervous system. WNT/β-catenin signaling is known to regulate the balance between the proliferation and differentiation of NPCs during neurogenesis. However, the function of WNT/β-catenin signaling during gliogenesis remains poorly defined. Here, we report that activation of WNT/β-catenin signaling disrupts astrogliogenesis in the developing spinal cord. Conversely, inhibition of WNT/β-catenin signaling leads to precocious astrogliogenesis...
March 19, 2019: Glia
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