Center-based Single-cell Models: An Approach to Multi-cellular Organization Based on a Conceptual Analogy to Colloidal Particles

Author(s):  
Dirk Drasdo
2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii311-iii312
Author(s):  
Bernhard Englinger ◽  
Johannes Gojo ◽  
Li Jiang ◽  
Jens M Hübner ◽  
McKenzie L Shaw ◽  
...  

Abstract Ependymoma represents a heterogeneous disease affecting the entire neuraxis. Extensive molecular profiling efforts have identified molecular ependymoma subgroups based on DNA methylation. However, the intratumoral heterogeneity and developmental origins of these groups are only partially understood, and effective treatments are still lacking for about 50% of patients with high-risk tumors. We interrogated the cellular architecture of ependymoma using single cell/nucleus RNA-sequencing to analyze 24 tumor specimens across major molecular subgroups and anatomic locations. We additionally analyzed ten patient-derived ependymoma cell models and two patient-derived xenografts (PDXs). Interestingly, we identified an analogous cellular hierarchy across all ependymoma groups, originating from undifferentiated neural stem cell-like populations towards different degrees of impaired differentiation states comprising neuronal precursor-like, astro-glial-like, and ependymal-like tumor cells. While prognostically favorable ependymoma groups predominantly harbored differentiated cell populations, aggressive groups were enriched for undifferentiated subpopulations. Projection of transcriptomic signatures onto an independent bulk RNA-seq cohort stratified patient survival even within known molecular groups, thus refining the prognostic power of DNA methylation-based profiling. Furthermore, we identified novel potentially druggable targets including IGF- and FGF-signaling within poorly prognostic transcriptional programs. Ependymoma-derived cell models/PDXs widely recapitulated the transcriptional programs identified within fresh tumors and are leveraged to validate identified target genes in functional follow-up analyses. Taken together, our analyses reveal a developmental hierarchy and transcriptomic context underlying the biologically and clinically distinct behavior of ependymoma groups. The newly characterized cellular states and underlying regulatory networks could serve as basis for future therapeutic target identification and reveal biomarkers for clinical trials.


Author(s):  
Jonathan Wong ◽  
Oscar Abilez ◽  
Ellen Kuhl

Channelrhodopsin-2 (ChR2) is a light-activated ion channel that can allow scientists to electrically activate cells via optical stimulation. Using a combination of existing computational electrophysiological and mechanical cardiac cell models with a novel ChR2 ion channel model, we created a model for ChR2-transduced cardiac myocytes. We implemented this model into a commonly available finite element platform and simulated both the single cell and the tissue electromechanical response. Our simulations show that it is possible to stimulate cardiac tissue optically with ChR2-transduced cells.


2012 ◽  
Vol 102 (3) ◽  
pp. 596a
Author(s):  
Anna A. Sher ◽  
Paul Carter ◽  
Blair Bethwaite ◽  
Denis Noble ◽  
David Abramson ◽  
...  

2016 ◽  
Vol 719 ◽  
pp. 9-13
Author(s):  
Zhuo Kai Qin ◽  
Jia Sheng Zhang ◽  
Yu Tian Yang ◽  
Jian Ju Luo ◽  
Wei Gao

Model constructing was conducted with 3D Studio Max modeling technology for hardwood minute structure in three steps. In the first step, the single-cell models were built according to the true form and shape of various kinds of cells, including vessel elements, wood-fiber cells, longitudinal parenchyma cells and ray cells. In the second step, the single-tissue models for all the four kinds of wood tissues (vessel, wood-fiber, longitudinal parenchyma and wood ray) were constructed by setting the same kind of single-cell models together according to the cell grouping ways inside true wood. In the third step, according to the distributing and arranging ways of the four kinds of wood tissues inside true wood, the whole model of wood block in minute structure was constructed by assembling the four kind of single-tissue models in a block. After that, the virtual model in computer was materialized by means of modern 3D printing technology, and finally the solid model in minute structure of Ficus microcarpa wood was constructed.


1999 ◽  
Vol 71 (1-3) ◽  
pp. 225-228 ◽  
Author(s):  
M.L Shuler
Keyword(s):  

2018 ◽  
Author(s):  
Simone Codeluppi ◽  
Lars E. Borm ◽  
Amit Zeisel ◽  
Gioele La Manno ◽  
Josina A. van Lunteren ◽  
...  

The global efforts towards the creation of a molecular census of the brain using single-cell transcriptomics is generating a large catalog of molecularly defined cell types lacking spatial information. Thus, new methods are needed to map a large number of cell-specific markers simultaneously on large tissue areas. Here, we developed a cyclic single molecule fluorescence in situ hybridization methodology and defined the cellular organization of the somatosensory cortex using markers identified by single-cell transcriptomics.


2021 ◽  
Author(s):  
Julien Lambert ◽  
Carla Lloret-Fernández ◽  
Lucie Laplane ◽  
Richard J. Poole ◽  
Sophie Jarriault

2008 ◽  
Vol 25 (2) ◽  
pp. 282-295 ◽  
Author(s):  
K. J. Kelleher ◽  
V. Hajdik ◽  
C. M. Colbert ◽  
K. Josić

2020 ◽  
Vol 31 (7) ◽  
pp. 511-519 ◽  
Author(s):  
Phi Luong ◽  
Qian Li ◽  
Pin-Fang Chen ◽  
Paul J. Wrighton ◽  
Denis Chang ◽  
...  

Retrograde membrane trafficking from plasma membrane to the Golgi and endoplasmic reticulum affects intracellular protein dynamics underlying cell function. Here, we developed split-fluorescent toxin reporters that enable a quantitative, sensitive, and real-time single-cell flow cytometry assay for retrograde membrane transport.


2019 ◽  
Vol 5 ◽  
pp. 4
Author(s):  
S. Telwatte ◽  
M. Montano ◽  
R. Resop ◽  
E. Battivelli ◽  
S. Morón-López ◽  
...  

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