The whole-cell pertussis vaccine imposes a broad effector B-cell response in mouse heterologous prime-boost settings

The authors compare effector and memory B cells induced by the two classes of pertussis vaccines (whole cell and acellular versions) using SORT-seq among other techniques. They show that a whole-cell pertussis vaccine prime achieves a more potent and broader memory B cell and plasma-cell response.

Thymosin B4 and prothymosin A promote cardiac regeneration post-ischemic injury in mice

This study uses SORT-seq to reveal the transcriptional profile of proliferating cardiomyocytes in the ischemic heart. It shows that overexpression of the two identified factors, TMSB4 and PTMA, can promote cardiac regeneration. A supportive environment seems to be critical for regeneration in addition to activating cardiomyocyte proliferation.

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.

A pendulum of induction between the epiblast and extra-embryonic endoderm supports post-implantation progression

Vrij et al. aim to elucidate the principles of epiblast and extraembryonic endoderm co-development in mice. SORT-seq and immunofluorescence microscopy analysis indicate a process of lineage bifurcation and the two layers sequentially inducing developmental progression in each other.

Molecular signatures and cellular diversity during mouse habenula development

The authors performed SORT-seq on mouse habenular neurons at critical developmental stages, instructed by detailed 3D anatomical data. The data reveal cellular and molecular trajectories during embryonic and postnatal development, leading to different habenular subtypes. Among these, the Cartpt+ neuron subtype was studied in-depth and successfully linked to specific molecular and functional properties.

Uncovering the mode of action of engineered T cells in patient cancer organoids

The authors developed a system called BEHAV3D to study the dynamic interactions of engineered T cells cultured with patient-derived solid-tumor organoids by imaging and (single-cell) transcriptomics. They identified a ‘super engager’ behavioral cluster of T cells with potent serial killing capacity. Then, they uncovered a behavior-specific gene expression signature in cancer metabolome-sensing engineered T cells and, finally, showed that type I interferon can prime resistant tumors for T cell killing.

Epicutaneous allergen immunotherapy induces a profound and selective modulation in skin dendritic cell subsets

A fast-expanding method in food allergy health is the epicutaneous allergen immunotherapy or patch test (“plakproef”). Laoubi et al. used SORT-seq, among other methods, to study the contribution of skin dendritic cells to T cell remodeling during patch tests. Their results emphasize that the cornerstone of food allergy desensitization is skin dendritic cells acquiring distinct specializations during the patch test.

Recurrent exon-deleting activating mutations in AHR act as drivers of urinary tract cancer

This paper documents the discovery of a new driver mutation in bladder cancer, present in ~10% of the studied cancer patients. The mutation is a deletion of exons 8 and 9 in the aryl hydrocarbon receptor (AHR) gene. SORT-seq analysis confirmed that a transformed, tumor-related expression profile arose due to mutated AHR in mouse bladder organoids.

p57Kip2 imposes the reserve stem cell state of gastric chief cells

Gastric chief cells are referred to as ‘reserve’ stem cells because they become proliferative and take part in regeneration after injury. The authors employed SORT-seq and doxycycline-based lineage tracing to reveal that p57Kip2 is a molecular switch for the reserve stem cell state of chief cells in mice.

BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states

Beumer et al. show that the bone morphogenetic protein (BMP) signaling pathway controls the creation of functional zones along the crypt-villus axis. A gene lipid uptake gene signature is enriched in the villus tip and could be therapeutically exploited with BMP inhibitors.

Single-cell profiling of human subventricular zone progenitors identifies SFRP1 as a target to re-activate progenitors

Progenitors of the adult brain’s subventricular zone remain mostly in a quiescent state. The mechanisms that regulate this quiescent state are still unclear. Here, the authors isolate progenitors for SORT-seq analysis, which revealed their identity as late oligodendrocyte progenitor cells. Then, they revealed the Wnt pathway antagonist SFRP1 as a possible signal that promotes the quiescence of progenitors.

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.