scholarly journals Conservation and Divergence of Related Neuronal Lineages in the Drosophila Central Brain

2019 ◽  
Author(s):  
Ying-Jou Lee ◽  
Ching-Po Yang ◽  
Yu-Fen Huang ◽  
Yisheng He ◽  
Qingzhong Ren ◽  
...  
Keyword(s):  
Stem Cells ◽  
Large Scale ◽  
Developmental Process ◽  
Morphological Diversity ◽  
Large Aggregate ◽  
Fixed Set ◽  
Central Brain ◽  
Specific Order ◽  
Identical Series ◽  
Lineage Mapping

SummaryWiring a complex brain requires enormous cell specificity. This specificity is laid out via a developmental process where neural stem cells produce countless diverse neurons. To help elucidate this process and resolve the considerable dynamic specificity, we need to observe the development of multiple neuronal lineages. Drosophila central brain lineages are predetermined, comprised of a fixed set of neurons born in pairs in a specific order. To reveal specific roles of lineage identity, Notch-dependent sister fate specification, and temporal patterning in morphological diversification, we mapped approximately one quarter of the Drosophila central brain lineages. While we found large aggregate differences, we also discovered similar patterns of morphological specification and diversification. Lineage identity plus Notch state govern primary neuronal trajectories, whereas temporal fates diversify terminal elaborations in target-specific manners. In addition, we identified ‘related’ lineages of analogous neuron types produced in similar temporal patterns. Two stem cells even yield identical series of dopaminergic neuron types, but with completely disparate sister neurons. These phenomena suggest that large changes in morphological diversity can be the consequence of relatively small differences in lineage fating. Taken together, this large-scale lineage mapping study reveals that relatively simple rules drive incredible neuronal complexity.

scholarly journals Conservation and divergence of related neuronal lineages in the Drosophila central brain

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ying-Jou Lee ◽  
Ching-Po Yang ◽  
Rosa L Miyares ◽  
Yu-Fen Huang ◽  
Yisheng He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Dopaminergic Neuron ◽  
Primary Neuron ◽  
Neuron Morphology ◽  
Large Aggregate ◽  
Cell Specificity ◽  
Central Brain ◽  
Specific Order ◽  
Identical Series

Wiring a complex brain requires many neurons with intricate cell specificity, generated by a limited number of neural stem cells. Drosophila central brain lineages are a predetermined series of neurons, born in a specific order. To understand how lineage identity translates to neuron morphology, we mapped 18 Drosophila central brain lineages. While we found large aggregate differences between lineages, we also discovered shared patterns of morphological diversification. Lineage identity plus Notch-mediated sister fate govern primary neuron trajectories, whereas temporal fate diversifies terminal elaborations. Further, morphological neuron types may arise repeatedly, interspersed with other types. Despite the complexity, related lineages produce similar neuron types in comparable temporal patterns. Different stem cells even yield two identical series of dopaminergic neuron types, but with unrelated sister neurons. Together, these phenomena suggest that straightforward rules drive incredible neuronal complexity, and that large changes in morphology can result from relatively simple fating mechanisms.

scholarly journals STEM-20. A CANCER STEM CELL-SELECTIVE APOPTOSIS-INDUCING SMALL MOLECULE FOR THE TREATMENT OF GBM

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii200-ii200
Author(s):  
Stephen Skirboll ◽  
Natasha Lucki ◽  
Genaro Villa ◽  
Naja Vergani ◽  
Michael Bollong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Small Molecules ◽  
Small Molecule ◽  
Large Scale ◽  
Critical Role ◽  
Tumor Formation ◽  
Cell Type ◽  
Caspase 1 ◽  
Activation Assay

Abstract INTRODUCTION Glioblastoma multiforme (GBM) is the most aggressive form of primary brain cancer. A subpopulation of multipotent cells termed GBM cancer stem cells (CSCs) play a critical role in tumor initiation and maintenance, drug resistance, and recurrence following surgery. New therapeutic strategies for the treatment of GBM have recently focused on targeting CSCs. Here we have used an unbiased large-scale screening approach to identify drug-like small molecules that induce apoptosis in GBM CSCs in a cell type-selective manner. METHODS A luciferase-based survival assay of patient-derived GBM CSC lines was established to perform a large-scale screen of ∼one million drug-like small molecules with the goal of identifying novel compounds that are selectively toxic to chemoresistant GBM CSCs. Compounds found to kill GBM CSC lines as compared to control cell types were further characterized. A caspase activation assay was used to evaluate the mechanism of induced cell death. A xenograft animal model using patient-derived GBM CSCs was employed to test the leading candidate for suppression of in vivo tumor formation. RESULTS We identified a small molecule, termed RIPGBM, from the cell-based chemical screen that induces apoptosis in primary patient-derived GBM CSC cultures. The cell type-dependent selectivity of RIPGBM appears to arise at least in part from redox-dependent formation of a proapoptotic derivative, termed cRIPGBM, in GBM CSCs. cRIPGBM induces caspase 1-dependent apoptosis by binding to receptor-interacting protein kinase 2 (RIPK2) and acting as a molecular switch, which reduces the formation of a prosurvival RIPK2/TAK1 complex and increases the formation of a proapoptotic RIPK2/caspase 1 complex. In an intracranial GBM xenograft mouse model, RIPGBM was found to significantly suppress tumor formation. CONCLUSIONS Our chemical genetics-based approach has identified a small molecule drug candidate and a potential drug target that selectively targets cancer stem cells and provides an approach for the treatment of GBMs.

Large-Scale Sources of Neural Stem Cells

2002 ◽  
Vol 25 (1) ◽  
pp. 381-407 ◽  
Author(s):  
David I. Gottlieb
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Large Scale

Large scale manufacturing strategy for production of umbilical cord-derived mesenchymal stem cells in support of clinical trials

Cytotherapy ◽  
2021 ◽  
Vol 23 (5) ◽  
pp. S166
Author(s):  
E. Linetsky ◽  
G. Lanzoni ◽  
X. Wang ◽  
C. Lenero ◽  
A. Patel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Large Scale ◽  
Manufacturing Strategy

Genetic and morphological diversity of the cosmopolitan chaetognath Pseudosagitta maxima (Conant, 1896) in the Atlantic Ocean and its relationship with the congeneric species

2017 ◽  
Vol 74 (7) ◽  
pp. 1875-1884 ◽  
Author(s):  
Dmitry N. Kulagin ◽  
Tatiana V. Neretina
Keyword(s):  
Atlantic Ocean ◽  
Large Scale ◽  
Phylogenetic Analyses ◽  
Morphological Diversity ◽  
Maturity Stage ◽  
Congeneric Species ◽  
Morphological Examination ◽  
Posterior Teeth ◽  
Biogeographic Patterns ◽  
True Diversity

Abstract Until recently many oceanic zooplankton species have been considered as cosmopolitan organisms. At present it became evident that some of them comprise many distinct molecular operational taxonomic units (MOTUs) that often are regarded as cryptic species. As they can significantly change our perceptions of large-scale biogeographic patterns, it is important to characterize the true diversity within common and ecologically important groups. We have analysed the molecular and morphological diversity of the cosmopolitan mesopelagic chaetognath Pseudosagitta maxima throughout the Atlantic Ocean from 60° S to 85° N and its position within the genus Pseudosagitta. Three distinct mitochondrial clades within P. maxima were revealed with phylogenetic analyses (Maximum Likelihood, Bayesian Inference) and were geographically separated. The subsequent analyses of nuclear markers (H3, ITS1) have shown that P. maxima most likely comprises two distinct MOTUs, tropical and bipolar, that also have some morphological differences. The latter MOTU consists of two genetically slightly divergent populations: southern and northern. The morphological examination allowed the determination of a character (type of hook coloration) that accurately distinguishes juveniles of the P. maxima complex from the other congeneric species. Molecular data have shown that evolutionary P. lyra and P. gazellae are more closely related to each other than to P. maxima. Number of hooks, number of anterior and posterior teeth and the arrangement of ova in the ovary were proposed to be the most useful morphological characters to distinguish between tropical and bipolar MOTUs within the P. maxima complex. The first three characters should be determined for each maturity stage separately.

scholarly journals Large-scale generation of human iPSC-derived neural stem cells/early neural progenitor cells and their neuronal differentiation

Organogenesis ◽  
2014 ◽  
Vol 10 (4) ◽  
pp. 365-377 ◽  
Author(s):  
Leonardo D’Aiuto ◽  
Yun Zhi ◽  
Dhanjit Kumar Das ◽  
Madeleine R Wilcox ◽  
Jon W Johnson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Progenitor Cells ◽  
Neuronal Differentiation ◽  
Large Scale ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Human Ipsc

Abstract 262: Derivation of Duchenne Muscular Dystrophy Disease Specific Cardiomyocytes From Patient Urine

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Xuan Guan ◽  
David L Mack ◽  
Claudia M Moreno ◽  
Fernando Santana ◽  
Charles E Murry ◽  
...  
Keyword(s):  
Stem Cells ◽  
Human Urine ◽  
Large Scale ◽  
Lentiviral Vector ◽  
Cellular Reprogramming ◽  
Urine Samples ◽  
Pcr Analysis ◽  
Scale Production ◽  
Mechanism Study

Introduction: Human somatic cells can be reprogrammed into primitive stem cells, termed induced pluripotent stem cells (iPSCs). These iPSCs can be extensively expanded in vitro and differentiated into multiple functional cell types, enabling faithful preservation of individual’s genotype and large scale production of disease targeted cellular components. These unique cellular reagents thus hold tremendous potential in disease mechanism study, drugs screening and cell replacement therapy. Due to the genetic mutation of the protein dystrophin, many DMD patients develop fatal cardiomyopathy with no effective treatment. The underlying pathogenesis has not been fully elucidated. Hypothesis: We tested the hypothesis that iPSCs could be generated from DMD patients’ urine samples and differentiated into cardiomyocytes, recapitulating the dystrophic phenotype. Methods: iPSCs generation was achieved by introducing a lentiviral vector expressing Oct4, Sox2, c-Myc and Klf4 into cells derived from patient’s (n=1) and healthy volunteers’ (n=3) urine. Cardiomyocytes were derived by sequentially treating iPSCs with GSK3 inhibitor CHIR99021 and Wnt inhibitor IWP4. Differentiated cardiomyocytes were subjected to calcium imaging, electrophysiology recording, Polymerase Chain Reaction (PCR) analysis, and immunostaining. Results: iPSCs were efficiently generated from human urine samples and further forced to differentiate into contracting cardiomyocytes. PCR analysis and immunostaining confirmed the expression of a panel of cardiac markers. Both normal and patient iPSC derived cardiomyocytes exhibited spontaneous and field stimulated calcium transients (up to 2Hz), as well as action potentials with ventricular-like and nodal-like characteristics. Anti-dystrophin antibodies stained normal iPSC-derived cardiomyocyte membranes but did not react against DMD iPSC-derived cardiomyocytes. Conclusions: Cardiomyocytes can be efficiently generated from human urine, through the cellular reprogramming technology. DMD cardiomyocytes retained the patient’s genetic information and manifested a dystrophin-null phenotype. Functional assessments are underway to determine differences that may exist between genotypes.

scholarly journals Lineage specification of early embryos and embryonic stem cells at the dawn of enabling technologies

2017 ◽  
Vol 4 (4) ◽  
pp. 533-542 ◽  
Author(s):  
Guangdun Peng ◽  
Patrick P. L. Tam ◽  
Naihe Jing
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Developmental Process ◽  
Embryonic Stem ◽  
Molecular Signaling ◽  
Lineage Specification ◽  
Genomic Technologies ◽  
Enabling Technologies ◽  
Stem Cell Pluripotency

Abstract Establishment of progenitor cell populations and lineage diversity during embryogenesis and the differentiation of pluripotent stem cells is a fascinating and intricate biological process. Conceptually, an understanding of this developmental process provides a framework to integrate stem-cell pluripotency, cell competence and differentiating potential with the activity of extrinsic and intrinsic molecular determinants. The recent advent of enabling technologies of high-resolution transcriptome analysis at the cellular, population and spatial levels proffers the capability of gaining deeper insights into the attributes of the gene regulatory network and molecular signaling in lineage specification and differentiation. In this review, we provide a snapshot of the emerging enabling genomic technologies that contribute to the study of development and stem-cell biology.

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