scholarly journals Single-Cell Transcriptomics Analyses of Neural Stem Cell Heterogeneity and Contextual Plasticity in a Zebrafish Brain Model of Amyloid Toxicity

Cell Reports ◽  
2019 ◽  
Vol 27 (4) ◽  
pp. 1307-1318.e3 ◽  
Author(s):  
Mehmet Ilyas Cosacak ◽  
Prabesh Bhattarai ◽  
Susanne Reinhardt ◽  
Andreas Petzold ◽  
Andreas Dahl ◽  
...  
Keyword(s):  
Stem Cell ◽  
Single Cell ◽  
Neural Stem Cell ◽  
Cell Heterogeneity ◽  
Zebrafish Brain ◽  
Amyloid Toxicity

scholarly journals Single-Cell Transcriptomics and Fate Mapping of Ependymal Cells Reveals an Absence of Neural Stem Cell Function

Cell ◽  
2018 ◽  
Vol 173 (4) ◽  
pp. 1045-1057.e9 ◽  
Author(s):  
Prajay T. Shah ◽  
Jo A. Stratton ◽  
Morgan Gail Stykel ◽  
Sepideh Abbasi ◽  
Sandeep Sharma ◽  
...  
Keyword(s):  
Stem Cell ◽  
Single Cell ◽  
Neural Stem Cell ◽  
Cell Function ◽  
Ependymal Cells ◽  
Fate Mapping

scholarly journals Single-cell molecular analysis defines therapy response and immunophenotype of stem cell subpopulations in CML

Blood ◽  
2017 ◽  
Vol 129 (17) ◽  
pp. 2384-2394 ◽  
Author(s):  
Rebecca Warfvinge ◽  
Linda Geironson ◽  
Mikael N. E. Sommarin ◽  
Stefan Lang ◽  
Christine Karlsson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Single Cell ◽  
Gene Expression Analysis ◽  
Therapy Response ◽  
Cell Heterogeneity ◽  
Key Points ◽  
Cell Gene Expression ◽  
Cell Subpopulations ◽  
Cell Gene

Key Points Single-cell gene expression analysis reveals CML stem cell heterogeneity and changes imposed by TKI therapy. A subpopulation with primitive, quiescent signature and increased survival to therapy can be high-purity captured as CD45RA−cKIT−CD26+.

scholarly journals Image analysis of neural stem cell division patterns in the zebrafish brain

2017 ◽  
Vol 93 (3) ◽  
pp. 314-322 ◽  
Author(s):  
Valerio Lupperger ◽  
Felix Buggenthin ◽  
Prisca Chapouton ◽  
Carsten Marr
Keyword(s):  
Image Analysis ◽  
Stem Cell ◽  
Cell Division ◽  
Neural Stem Cell ◽  
Zebrafish Brain ◽  
Stem Cell Division

scholarly journals Single-Cell Transcriptomic Analysis Defines Heterogeneity and Transcriptional Dynamics in the Adult Neural Stem Cell Lineage

Cell Reports ◽  
2017 ◽  
Vol 18 (3) ◽  
pp. 777-790 ◽  
Author(s):  
Ben W. Dulken ◽  
Dena S. Leeman ◽  
Stéphane C. Boutet ◽  
Katja Hebestreit ◽  
Anne Brunet
Keyword(s):  
Stem Cell ◽  
Single Cell ◽  
Neural Stem Cell ◽  
Cell Lineage ◽  
Transcriptomic Analysis ◽  
Adult Neural Stem Cell ◽  
Transcriptional Dynamics ◽  
Stem Cell Lineage

Functional Evaluation of Neural Stem Cell Differentiation by Single Cell Calcium Imaging

2011 ◽  
Vol 6 (3) ◽  
pp. 288-296 ◽  
Author(s):  
Maria Francisca Eiriz ◽  
Sofia Grade ◽  
Alexandra Rosa ◽  
Sara Xapelli ◽  
Liliana Bernardino ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Single Cell ◽  
Neural Stem Cell ◽  
Calcium Imaging ◽  
Stem Cell Differentiation ◽  
Functional Evaluation ◽  
Cell Calcium

scholarly journals Transcriptional and Functional Description of Stem Cell Heterogeneity in Native and Transplantation Hematopoiesis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3844-3844
Author(s):  
Alejo E Rodriguez-Fraticelli ◽  
Caleb Weinreb ◽  
Allon Moshe Klein ◽  
Fernando Camargo
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Steady State ◽  
Hematopoietic Stem Cells ◽  
Single Cell ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Significant Proportion ◽  
Cell Heterogeneity ◽  
Hematopoietic Stem

Abstract The hematopoietic system follows a hierarchical organization, with multipotent long-term repopulating hematopoietic stem cells (LT-HSCs) occupying the top tier. This paradigm, developed mostly through cell transplantation assays, has recently been contested by a series of studies performed under native conditions, without transplantation. Application of systems-level single cell methods in this setting has revealed a heterogeneity of cell states within progenitors and stem cells, prompting a reevaluation of the theories of hematopoietic lineage fate decisions. We have previously described that hematopoietic stem cell fates are clonally heterogeneous under steady state and uncovered that a fraction of LT-HSCs contributes to a significant proportion of the megakaryocytic cell lineage under steady state, while rarely generating other types of progeny in unperturbed conditions. To elucidate the molecular underpinnings of this functional lineage-output heterogeneity, we developed a technique to barcode hematopoietic cells at the RNA level in order to simultaneously capture the lineage relationships and transcriptional states of HSCs. Using a droplet-based massive single cell RNAseq platform, we analyzed thousands of engrafted hematopoietic stem cells together with a sufficiently significant representation of downstream progenitor cells to measure HSC output. Inspection of the resulting "stem cell state-fate maps" revealed a variety of stem cell behaviors, including single cell quiescence, asymmetric and symmetric divisions, and clonal expansion. We also connected these behaviors with some of the previously observed heterogeneity in stem cell outcomes, including lineage bias, lineage output and clonal competition. Importantly, clustering of expression profiles revealed significant differences in the transcriptional programs related with some of these behaviors, which illuminate the molecular machineries that operate at the stem cell level to define this heterogeneity. Thus, our work has identified potential novel mediators for stem cell heterogeneity, which we are functionally analyzing in further detail to understand their molecular mechanisms. Disclosures No relevant conflicts of interest to declare.

scholarly journals KYNA/Ahr Signaling Suppresses Neural Stem Cell Plasticity and Neurogenesis in Adult Zebrafish Model of Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2748
Author(s):  
Tohid Siddiqui ◽  
Prabesh Bhattarai ◽  
Stanislava Popova ◽  
Mehmet Ilyas Cosacak ◽  
Sanjeev Sariya ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Late Onset ◽  
Association Studies ◽  
Neural Regeneration ◽  
Adult Zebrafish ◽  
Amyloid Toxicity ◽  
Model Of Alzheimer’S Disease

Neurogenesis decreases in Alzheimer’s disease (AD) patients, suggesting that restoring the normal neurogenic response could be a disease modifying intervention. To study the mechanisms of pathology-induced neuro-regeneration in vertebrate brains, zebrafish is an excellent model due to its extensive neural regeneration capacity. Here, we report that Kynurenic acid (KYNA), a metabolite of the amino acid tryptophan, negatively regulates neural stem cell (NSC) plasticity in adult zebrafish brain through its receptor, aryl hydrocarbon receptor 2 (Ahr2). The production of KYNA is suppressed after amyloid-toxicity through reduction of the levels of Kynurenine amino transferase 2 (KAT2), the key enzyme producing KYNA. NSC proliferation is enhanced by an antagonist for Ahr2 and is reduced with Ahr2 agonists or KYNA. A subset of Ahr2-expressing zebrafish NSCs do not express other regulatory receptors such as il4r or ngfra, indicating that ahr2-positive NSCs constitute a new subset of neural progenitors that are responsive to amyloid-toxicity. By performing transcriptome-wide association studies (TWAS) in three late onset Alzheimer disease (LOAD) brain autopsy cohorts, we also found that several genes that are components of KYNA metabolism or AHR signaling are differentially expressed in LOAD, suggesting a strong link between KYNA/Ahr2 signaling axis to neurogenesis in LOAD.

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