scholarly journals Growing Glia: Cultivating Human Stem Cell Models of Gliogenesis in Health and Disease

Author(s):  
Samantha N. Lanjewar ◽  
Steven A. Sloan

Glia are present in all organisms with a central nervous system but considerably differ in their diversity, functions, and numbers. Coordinated efforts across many model systems have contributed to our understanding of glial-glial and neuron-glial interactions during nervous system development and disease, but human glia exhibit prominent species-specific attributes. Limited access to primary samples at critical developmental timepoints constrains our ability to assess glial contributions in human tissues. This challenge has been addressed throughout the past decade via advancements in human stem cell differentiation protocols that now offer the ability to model human astrocytes, oligodendrocytes, and microglia. Here, we review the use of novel 2D cell culture protocols, 3D organoid models, and bioengineered systems derived from human stem cells to study human glial development and the role of glia in neurodevelopmental disorders.

2020 ◽  
Author(s):  
Elizaveta Fofanova ◽  
Tatiana Mayorova ◽  
Elena Voronezhskaya

Abstract BackgroundThe structure and development of the nervous system in Lophotrochozoa species is of the most important questions for comparative neurobiology. During the last decade the number of comprehensive studies on the development of serotonergic and FMRFamidergic systems has been skyrocketing. However, the detailed research of the earliest events of Polychaeta neurogenesis is still sparce. Polychaeta is a huge taxon within Lophotrochozoa. Its representatives are widely used as model systems in developmental and physiological investigations. Dinophilidae is a unique Polychaeta group. Its representatives combine morphological traits of different lophotrochozoan taxa. Moreover, adult dinophilids demonstrate morphological similarity to a trochophore larva. This similarity may be associated with either archaic origin of this group or neoteny. The main goal of our study is to provide a detailed description of the earliest events in Dinophilus neurogenesis. These data might improve our understanding of Polychaeta development and evolution.ResultsWe have studied the earliest events in nervous system development in two relative species D. gyrociliatus and D. taeniatus using immunochemical labelling of serotonin, FMRF-amide related peptides, and acetylated tubulin. We used external ciliation as marker for staging. Both species go through the same developmental stages: prototroch, ventral ciliary field and ciliary bands. In both species the first neurons differenciate revealed by anti alpha-acetylated tubulin antibodies only and show no reaction with 5-HT or FMRFa antibodies. These neurons located at the anterior and posterior parts of the embryo in both species. In D. taeniatus embryons the anterior cell is transient and disappear just after head neuropil is constructed. On the contrary, in D. gyrociliatus embryos the anterior cell is not transient and remains at the same position during the whole life span of the specimen. Caudal cell is present during the whole embryogenesis in both species. Neurites of these early neurons surround the stomadeum and constitute anlagen of paired ventro-lateral longitudinal bundles. During the development the number of neurites increases and they form compact head neuropil, paired ventro-lateral and lateral longitudinal bundles, unpaired medial longitudinal bundle and transverse commissures in ventral hyposphere. Serotonin- and FMRFamide-immunoreactive neurons differentiate adjacent to ventro-lateral bundles and head neuropil, respectively, after the establishment of main structures of the nervous system at the ventral ciliary field and ciliary bands stages. Processes of serotonin-, FMRFamide- immunopositive neurons constitute the small portion of tubulin immunopositive neuropil at all described stages.ConclusionsWe announce a detailed data on the earliest events in D. gyrociliatus and D. taeniatus neurodevelopment based on anti-acetylated tubulin, serotonin, and FMRFamide-like immuno labeling. The first nerve elements demonstrate no 5-HT-IR and no FMRFa-IR, which differs from the most Polychaetes and even Lophotrochozoans, investigated so far. Moreover, these animals do not have a typical apical organ (or perhaps do not have it at all) and the pioneer neurons of D.gyrociliatus are also peculiar in that they join the definitive nervous system unlike other lophotrochozoans where pioneer nerons are transient. Thus, Dinophilus neurogenesis demonstrates a variation of common scheme. The reported study was funded by RFBR, project number 19-3460040.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Luiz Henrique Medeiros Geraldo ◽  
Tânia Cristina Leite de Sampaio Spohr ◽  
Rackele Ferreira do Amaral ◽  
Anna Carolina Carvalho da Fonseca ◽  
Celina Garcia ◽  
...  

AbstractLysophosphatidic acid (LPA) is an abundant bioactive phospholipid, with multiple functions both in development and in pathological conditions. Here, we review the literature about the differential signaling of LPA through its specific receptors, which makes this lipid a versatile signaling molecule. This differential signaling is important for understanding how this molecule can have such diverse effects during central nervous system development and angiogenesis; and also, how it can act as a powerful mediator of pathological conditions, such as neuropathic pain, neurodegenerative diseases, and cancer progression. Ultimately, we review the preclinical and clinical uses of Autotaxin, LPA, and its receptors as therapeutic targets, approaching the most recent data of promising molecules modulating both LPA production and signaling. This review aims to summarize the most update knowledge about the mechanisms of LPA production and signaling in order to understand its biological functions in the central nervous system both in health and disease.


2020 ◽  
Vol 21 (19) ◽  
pp. 6980
Author(s):  
Satish Kumar ◽  
Joanne E. Curran ◽  
Erica DeLeon ◽  
Ana C. Leandro ◽  
Tom E. Howard ◽  
...  

miRNA regulates the expression of protein coding genes and plays a regulatory role in human development and disease. The human iPSCs and their differentiated progenies provide a unique opportunity to identify these miRNA-mediated regulatory mechanisms. To identify miRNA–mRNA regulatory interactions in human nervous system development, well characterized NSCs were differentiated from six validated iPSC lines and analyzed for differentially expressed (DE) miRNome and transcriptome by RNA sequencing. Following the criteria, moderated t statistics, FDR-corrected p-value ≤ 0.05 and fold change—absolute (FC-abs) ≥2.0, 51 miRNAs and 4033 mRNAs were found to be significantly DE between iPSCs and NSCs. The miRNA target prediction analysis identified 513 interactions between 30 miRNA families (mapped to 51 DE miRNAs) and 456 DE mRNAs that were paradoxically oppositely expressed. These 513 interactions were highly enriched in nervous system development functions (154 mRNAs; FDR-adjusted p-value range: 8.06 × 10−15–1.44 × 10−4). Furthermore, we have shown that the upregulated miR-10a-5p, miR-30c-5p, miR23-3p, miR130a-3p and miR-17-5p miRNA families were predicted to down-regulate several genes associated with the differentiation of neurons, neurite outgrowth and synapse formation, suggesting their role in promoting the self-renewal of undifferentiated NSCs. This study also provides a comprehensive characterization of iPSC-generated NSCs as dorsal neuroepithelium, important for their potential use in in vitro modeling of human brain development and disease.


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