Co-Culture of Glomerular Endothelial Cells and Podocytes in a Custom-Designed Glomerulus-on-a-Chip Model Improves the Filtration Barrier Integrity and Affects the Glomerular Cell Phenotype

The authors delevoped co-culturing methods for glomerulus endothelial and epithelial cells for the glomerulus-on-a-chip technology. Specifically, with RNA-seq, they investigated the effect of crosstalk between the two cells on their transcriptome, which was shown to affect differentiation and adhesion programs.

The EMT transcription factor ZEB1 governs a fitness-promoting but vulnerable DNA replication stress response

The authors discover a chemoresistant ZEB1-high-expressing subpopulation of cancer cells. Then, they use SORT-seq to study the transcriptomes of ZEB1-high- and low-expressing cells. They find changes in cell cycle progression and DNA damage response, which creates stress resistance. This is found to, at the same time, create a targetable vulnerability in chemoresistant ZEB1-high-expressing cancer cells, which could be exploited in therapy.

Mammalian life depends on two distinct pathways of DNA damage tolerance

The team applied SORT-seq on mouse embryos to investigate how DNA damage toleration (DDT) deficiency affected the hematopoietic stem cell subset in the so-called LSK compartment. Ultimately, DDT deficiency results in DNA damage accumulation and depletion of hematopoietic stem cells. Meanwhile, it promotes the survival of cells expressing erythroid transcription factor KLF1. These insights indicate a novel molecular mechanism that regulates hematopoietic output in response to DNA damage.

JAG1-NOTCH4 mechanosensing drives atherosclerosis

Heart attack and stroke can be caused by endothelial cell–triggered atherosclerosis. This paper shows that disturbed blood flow activates the JAG1-NOTCH4 signaling pathway. SORT-seq analysis indicates Jag1 suppresses proliferative endothelial cells, enhancing atherosclerosis susceptibility.

Exposure to the Amino Acids Histidine, Lysine, and Threonine Reduces mTOR Activity and Affects Neurodevelopment in a Human Cerebral Organoid Model

The authors pioneered the use of human cerebral organoids to investigate the impact of amino acid supplementation on neurodevelopment. RNA sequencing identified gene expression changes after supplementation, with enrichment in genes related to mTOR signaling and immune function, a.o., and to specific cell types, including proliferative precursor cells, microglia, and astrocytes.

Linking the genotypes and phenotypes of cancer cells in heterogenous populations via real-time optical tagging and image analysis

This paper describes how cells can be optically tagged in real-time based on specific functional cell dynamics, such as fast migration or morphological variation. Moreover, it documents how you can combine optical tagging with single-cell RNA sequencing to link the genotypes and phenotypes of heterogenous tumor populations.

Time-resolved single-cell sequencing identifies multiple waves of mRNA decay during the mitosis-to-G1 phase transition

The authors show that scheduled mRNA decay helps to reshape cell cycle gene expression as cells move from mitosis into G1 phase. To obtain a detailed view of mRNA levels as cells progress from M phase into G1 phase, they developed an original method that connects live-cell microscopy with SORT-seq.

Lipid droplet availability affects neural stem/progenitor cell metabolism and proliferation

This paper investigates the role of lipid droples in the regulation of neural stem/progenitor cells. Using SORT-seq among other techniques, the authors show that lipid droplets are highly abundant in adult mouse neural stem/progenitor cells, and suggest that lipid droplet levels influence their metabolism and cell fate.

Functional single cell selection and annotated profiling of dynamically changing cancer cells

You et al. present FUN-seq, a combination of functional single-cell selection, using microscopic tagging and FACS, and SORT-seq. Applied to cultured tumor cells, it shines a light on the transcriptional processes underlying the epithelial-to-mesenchymal transition.