Biology subjects

Zhemkov, V.

Publications and source records attributed to Zhemkov, V..

3 recordsLinked to original sources

bioRxiv2026

Single-cell proteomic maps of human induced pluripotent stem cells and their differentiation into motor neurons

The majority of single cell-studies use RNA to identify the cell state. However, many RNAs are transient and decrease in response to elevated protein to control homeostasis. Thus, final cell states are largely defined by their unique and dynamic protein composition not RNA. Here a single-cell proteomics approach was used to identify the proteomic profile of human induced pluripotent stem cells (iPSCs) before and during their in vitro differentiation to motor neurons. By measuring up to 1000 proteins in each cell, novel clusters of growing iPSCs could be characterized along with a new proteomic pathway that defines motor neuron development. Interestingly, there was a dynamic and cell type-specific discordance between the protein levels and their corresponding messenger RNAs. This lays the foundation for drawing new single-cell proteomic maps of developing human tissues. IN BRIEFIn this article, we report the first single-cell proteomic maps of induced pluripotent stem cells (iPSCs) and their differentiation into motor neurons (MNs). By identifying proteomes of individual cells, we resolve iPSC and MN states, their proteomic, metabolomic and organellar heterogeneity. We show considerable, stage-specific discordance between the transcriptome and the proteome in differentiated neurons.

neuroscience↗

bioRxiv2020

The role of sigma-1 receptor in organization of endoplasmic reticulum signaling microdomains

Sigma 1 receptor (S1R) is a 223 amino acid-long transmembrane endoplasmic reticulum (ER) protein. S1R modulates activity of multiple effector proteins but its signaling functions are poorly understood. We here test the hypothesis that biological activity of S1R in cells can be explained by its ability to interact with cholesterol and to form cholesterol-enriched microdomains in the ER. Using reduced reconstitution systems, we demonstrate direct effects of cholesterol on S1R clustering. We identify a novel cholesterol-binding motif in the transmembrane region of S1R and demonstrate its importance for S1R clustering. We demonstrate that S1R-induced membrane microdomains have increased local membrane thickness. Increased local cholesterol concentration and membrane thickness in these domains can modulate signaling of inositol-requiring enzyme 1 (IRE1) in the ER. Further, S1R agonists cause reduction in S1R clusters, suggesting that biological activity of S1R agonists is linked to remodeling of ER membrane microdomains.

cell biology↗

bioRxiv2019

Light-sheet microscopy with isotropic, sub-micron resolution and solvent-independent large-scale imaging

We present cleared tissue Axially Swept Light-Sheet Microscopy (ctASLM), which achieves sub-micron isotropic resolution, high optical sectioning capability, and large field of view imaging (870x870 m2) over a broad range of immersion media. ctASLM can image live, expanded, and both aqueous and organic chemically cleared tissue preparations and provides 2- to 5-fold better axial resolution than confocal or other reported cleared tissue light-sheet microscopes. We image millimeter-sized tissues with sub-micron 3D resolution, which enabled us to perform automated detection of cells and subcellular features such as dendritic spines.

bioengineering↗