Dataset Information

Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips.

ABSTRACT: In vitro neuronal models are essential for studying neurological physiology, disease mechanisms and potential treatments. Most in vitro models lack controlled vasculature, despite its necessity in brain physiology and disease. Organ-on-chip models offer microfluidic culture systems with dedicated micro-compartments for neurons and vascular cells. Such multi-cell type organs-on-chips can emulate neurovascular unit (NVU) physiology, however there is a lack of systematic data on how individual cell types are affected by culturing on microfluidic systems versus conventional culture plates. This information can provide perspective on initial findings of studies using organs-on-chip models, and further optimizes these models in terms of cellular maturity and neurovascular physiology. Here, we analysed the transcriptomic profiles of co-cultures of human induced pluripotent stem cell (hiPSC)-derived neurons and rat astrocytes, as well as one-day monocultures of human endothelial cells, cultured on microfluidic chips. For each cell type, large gene expression changes were observed when cultured on microfluidic chips compared to conventional culture plates. Endothelial cells showed decreased cell division, neurons and astrocytes exhibited increased cell adhesion, and neurons showed increased maturity when cultured on a microfluidic chip. Our results demonstrate that culturing NVU cell types on microfluidic chips changes their gene expression profiles, presumably due to distinct surface-to-volume ratios and substrate materials. These findings inform further NVU organ-on-chip model optimization and support their future application in disease studies and drug testing.

SUBMITTER: Middelkamp HHT

PROVIDER: S-EPMC7838281 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips.

Middelkamp H H T HHT Verboven A H A AHA De Sá Vivas A G AG Schoenmaker C C Klein Gunnewiek T M TM Passier R R Albers C A CA 't Hoen P A C PAC Nadif Kasri N N van der Meer A D AD

Scientific reports 20210126 1

In vitro neuronal models are essential for studying neurological physiology, disease mechanisms and potential treatments. Most in vitro models lack controlled vasculature, despite its necessity in brain physiology and disease. Organ-on-chip models offer microfluidic culture systems with dedicated micro-compartments for neurons and vascular cells. Such multi-cell type organs-on-chips can emulate neurovascular unit (NVU) physiology, however there is a lack of systematic data on how individual cell ...[more]

PMID: 33500551

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Project description:Secreted factors play a central role in normal and pathological processes in every tissue in the body. The brain is composed of a highly complex milieu of different cell types and few methods exist that can identify which individual cells in a complex mixture are secreting specific analytes. By identifying which cells are responsible, we can better understand neural physiology and pathophysiology, more readily identify the underlying pathways responsible for analyte production, and ultimately use this information to guide the development of novel therapeutic strategies that target the cell types of relevance. We present here a method for detecting analytes secreted from single human induced pluripotent stem cell (iPSC)-derived neural cells and have applied the method to measure amyloid ? (A?) and soluble amyloid precursor protein-alpha (sAPP?), analytes central to Alzheimer's disease pathogenesis. Through these studies, we have uncovered the dynamic range of secretion profiles of these analytes from single iPSC-derived neuronal and glial cells and have molecularly characterized subpopulations of these cells through immunostaining and gene expression analyses. In examining A? and sAPP? secretion from single cells, we were able to identify previously unappreciated complexities in the biology of APP cleavage that could not otherwise have been found by studying averaged responses over pools of cells. This technique can be readily adapted to the detection of other analytes secreted by neural cells, which would have the potential to open new perspectives into human CNS development and dysfunction.We have established a technology that, for the first time, detects secreted analytes from single human neurons and astrocytes. We examine secretion of the Alzheimer's disease-relevant factors amyloid ? (A?) and soluble amyloid precursor protein-alpha (sAPP?) and present novel findings that could not have been observed without a single-cell analytical platform. First, we identify a previously unappreciated subpopulation that secretes high levels of A? in the absence of detectable sAPP?. Further, we show that multiple cell types secrete high levels of A? and sAPP?, but cells expressing GABAergic neuronal markers are overrepresented. Finally, we show that astrocytes are competent to secrete high levels of A? and therefore may be a significant contributor to A? accumulation in the brain.

Dataset Information

Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips.

Publications

Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips.

Similar Datasets

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