scholarly journals Universal Microfluidic System for Analysis and Control of Cell Dynamics

2017 ◽  
Author(s):  
Ce Zhang ◽  
Hsiung-Lin Tu ◽  
Gengjie Jia ◽  
Tanzila Mukhtar ◽  
Verdon Taylor ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Single Cells ◽  
Stem Cell Differentiation ◽  
Microfluidic System ◽  
Cell Dynamics ◽  
Point Analysis ◽  
Wide Range ◽  
Microfluidic Cell Culture ◽  
Cellular Logic

SUMMARYDynamical control of the cellular microenvironment is highly desired for quantitative studies of stem cells and immune signaling. Here, we present an automated microfluidic system for high-throughput culture, differentiation and analysis of a wide range of cells in precisely defined dynamic microenvironments recapitulating cellular niches. This system delivers complex, time-varying biochemical signals to 1,500 independently programmable cultures containing either single cells, 2-D populations, or 3-D organoids, and dynamically stimulates adherent or non-adherent cells while tracking and retrieving them for end-point analysis. Using this system, we investigated the signaling landscape of neural stem cell differentiation under combinatorial and dynamic stimulation with growth factors. Experimental and computational analyses identified “cellular logic rules” for stem cell differentiation, and demonstrated the importance of signaling sequence and timing in brain development. This universal platform greatly enhances capabilities of microfluidic cell culture, allows dissection of previously hidden aspects of cellular dynamics, and enables accelerated biological discovery.

Wide-range stiffness gradient PVA/HA hydrogel to investigate stem cell differentiation behavior

2016 ◽  
Vol 35 ◽  
pp. 23-31 ◽  
Author(s):  
Se Heang Oh ◽  
Dan Bi An ◽  
Tae Ho Kim ◽  
Jin Ho Lee
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Stem Cell Differentiation ◽  
Wide Range

scholarly journals Transformative opportunities for single-cell proteomics

2018 ◽  
Author(s):  
Harrison Specht ◽  
Nikolai Slavov
Keyword(s):  
Mass Spectrometry ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Single Cell ◽  
Single Cells ◽  
Biological Systems ◽  
Stem Cell Differentiation ◽  
New Age ◽  
Technological Developments

Many pressing medical challenges - such as diagnosing disease, enhancing directed stem cell differentiation, and classifying cancers - have long been hindered by limitations in our ability to quantify proteins in single cells. Mass-spectrometry (MS) is poised to transcend these limitations by developing powerful methods to routinely quantify thousands of proteins and proteoforms across many thousands of single cells. We outline specific technological developments and ideas that can increase the sensitivity and throughput of single cell MS by orders of magnitude and usher in this new age. These advances will transform medicine and ultimately contribute to understanding biological systems on an entirely new level.

scholarly journals Gold Nanowires/Fibrin Nanostructure as Microfluidics Platforms for Enhancing Stem Cell Differentiation: Bio-AFM Study

Micromachines ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 50 ◽  
Author(s):  
Hashemzadeh ◽  
Allahverdi ◽  
Ghorbani ◽  
Soleymani ◽  
Kocsis ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Stem Cell Differentiation ◽  
Physical Parameters ◽  
Gold Nanowires ◽  
Matrix Elasticity ◽  
Cell Chip ◽  
Chip Technology ◽  
Wide Range ◽  
Organ On A Chip

Organ-on-a-chip technology has gained great interest in recent years given its ability to control the spatio-temporal microenvironments of cells and tissues precisely. While physical parameters of the respective niche such as microchannel network sizes, geometric features, flow rates, and shear forces, as well as oxygen tension and concentration gradients, have been optimized for stem cell cultures, little has been done to improve cell-matrix interactions in microphysiological systems. Specifically, detailed research on the effect of matrix elasticity and extracellular matrix (ECM) nanotopography on stem cell differentiation are still in its infancy, an aspect that is known to alter a stem cell’s fate. Although a wide range of hydrogels such as gelatin, collagen, fibrin, and others are available for stem cell chip cultivations, only a limited number of elasticities are generally employed. Matrix elasticity and the corresponding nanotopography are key factors that guide stem cell differentiation. Given this, we investigated the addition of gold nanowires into hydrogels to create a tunable biointerface that could be readily integrated into any organ-on-a-chip and cell chip system. In the presented work, we investigated the matrix elasticity (Young’s modulus, stiffness, adhesive force, and roughness) and nanotopography of gold nanowire loaded onto fibrin hydrogels using the bio-AFM (atomic force microscopy) method. Additionally, we investigated the capacity of human amniotic mesenchymal stem cells (hAMSCs) to differentiate into osteo- and chondrogenic lineages. Our results demonstrated that nanogold structured-hydrogels promoted differentiation of hAMSCs as shown by a significant increase in Collagen I and II production. Additionally, there was enhanced calcium mineralization activity and proteoglycans formation after a cultivation period of two weeks within microfluidic devices.

scholarly journals Bioconductor workflow for single-cell RNA sequencing: Normalization, dimensionality reduction, clustering, and lineage inference

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1158 ◽  
Author(s):  
Fanny Perraudeau ◽  
Davide Risso ◽  
Kelly Street ◽  
Elizabeth Purdom ◽  
Sandrine Dudoit
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Dimensionality Reduction ◽  
Single Cell ◽  
Single Cells ◽  
Differential Expression Analysis ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Cell Clustering ◽  
Cell Transcriptome

Novel single-cell transcriptome sequencing assays allow researchers to measure gene expression levels at the resolution of single cells and offer the unprecendented opportunity to investigate at the molecular level fundamental biological questions, such as stem cell differentiation or the discovery and characterization of rare cell types. However, such assays raise challenging statistical and computational questions and require the development of novel methodology and software. Using stem cell differentiation in the mouse olfactory epithelium as a case study, this integrated workflow provides a step-by-step tutorial to the methodology and associated software for the following four main tasks: (1) dimensionality reduction accounting for zero inflation and over dispersion and adjusting for gene and cell-level covariates; (2) cell clustering using resampling-based sequential ensemble clustering; (3) inference of cell lineages and pseudotimes; and (4) differential expression analysis along lineages.

scholarly journals Ultra-multiplexed analysis of single-cell dynamics reveals logic rules in differentiation

2019 ◽  
Vol 5 (4) ◽  
pp. eaav7959 ◽  
Author(s):  
Ce Zhang ◽  
Hsiung-Lin Tu ◽  
Gengjie Jia ◽  
Tanzila Mukhtar ◽  
Verdon Taylor ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Single Cell ◽  
Cell Fate ◽  
Single Cell Analysis ◽  
Single Cells ◽  
Critical Role ◽  
Stem Cell Differentiation ◽  
Cell Fate Decisions ◽  
Cellular Microenvironments

Dynamical control of cellular microenvironments is highly desirable to study complex processes such as stem cell differentiation and immune signaling. We present an ultra-multiplexed microfluidic system for high-throughput single-cell analysis in precisely defined dynamic signaling environments. Our system delivers combinatorial and time-varying signals to 1500 independently programmable culture chambers in week-long live-cell experiments by performing nearly 106 pipetting steps, where single cells, two-dimensional (2D) populations, or 3D neurospheres are chemically stimulated and tracked. Using our system and statistical analysis, we investigated the signaling landscape of neural stem cell differentiation and discovered “cellular logic rules” that revealed the critical role of signal timing and sequence in cell fate decisions. We find synergistic and antagonistic signal interactions and show that differentiation pathways are highly redundant. Our system allows dissection of hidden aspects of cellular dynamics and enables accelerated biological discovery.

scholarly journals Transformative opportunities for single-cell proteomics

2018 ◽  
Author(s):  
Harrison Specht ◽  
Nikolai Slavov
Keyword(s):  
Mass Spectrometry ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Single Cell ◽  
Single Cells ◽  
Biological Systems ◽  
Stem Cell Differentiation ◽  
New Age ◽  
Technological Developments

Many pressing medical challenges - such as diagnosing disease, enhancing directed stem cell differentiation, and classifying cancers - have long been hindered by limitations in our ability to quantify proteins in single cells. Mass-spectrometry (MS) is poised to transcend these limitations by developing powerful methods to routinely quantify thousands of proteins and proteoforms across many thousands of single cells. We outline specific technological developments and ideas that can increase the sensitivity and throughput of single cell MS by orders of magnitude and usher in this new age. These advances will transform medicine and ultimately contribute to understanding biological systems on an entirely new level.

scholarly journals Routinely quantifying single cell proteomes: A new age in quantitative biology and medicine

2018 ◽  
Author(s):  
Harrison Specht ◽  
Nikolai Slavov
Keyword(s):  
Mass Spectrometry ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Single Cell ◽  
Single Cells ◽  
Biological Systems ◽  
Stem Cell Differentiation ◽  
New Age ◽  
Quantitative Biology ◽  
Technological Developments

Many pressing medical challenges -- such as diagnosing disease, enhancing directed stem cell differentiation, and classifying cancers -- have long been hindered by limitations in our ability to quantify proteins in single cells. Mass-spectrometry (MS) is poised to transcend these limitations by developing powerful methods to routinely quantify thousands of proteins and proteoforms across many thousands of single cells. We outline specific technological developments and ideas that can increase the sensitivity and throughput of single cell MS by orders of magnitude and usher in this new age. These advances will transform medicine and ultimately contribute to understanding biological systems on an entirely new level.

scholarly journals A theoretical framework to study the influence of electrical fields on mesenchymal stem cells

2020 ◽  
Author(s):  
Jonathan Dawson ◽  
Poh Soo Lee ◽  
Ursula van Rienen ◽  
Revathi Appali
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Electric Field ◽  
Applied Electric Field ◽  
Stem Cell Differentiation ◽  
Theoretical Framework ◽  
Cell Dynamics ◽  
The Individual

ABSTRACTMesenchymal stem cell dynamics involves cell proliferation and cell differentiation into cells of distinct functional type, such as osteoblasts, adipocytes, or chondrocytes. Electrically active implants influence these dynamics for the regeneration of the cells in damaged tissues. How applied electric field influences processes of individual stem cells is a problem mostly unaddressed. The mathematical approaches to study stem cell dynamics have focused on the stem cell population as a whole, without resolving individual cells and intracellular processes. In this paper, we present a theoretical framework to describe the dynamics of a population of stem cells, taking into account the processes of the individual cells. We study the influence of the applied electric field on the cellular processes. We test our mean-field theory with the experiments from the literature, involving in vitro electrical stimulation of stem cells. We show that a simple model can quantitatively describe the experimentally observed time-course behavior of the total number of cells and the total alkaline phosphate activity in a population of mesenchymal stem cells. Our results show that the stem cell differentiation rate is dependent on the applied electrical field, confirming published experimental findings. Moreover, our analysis supports the cell density-dependent proliferation rate. Since the experimental results are averaged over many cells, our theoretical framework presents a robust and sensitive method for determining the effect of applied electric fields at the scale of the individual cell. These results indicate that the electric field stimulation may be effective in promoting bone regeneration by accelerating osteogenic differentiation.

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