eLife October, 2022 by Alexandra Wiesinger et al.
A single cell transcriptional roadmap of human pacemaker cell differentiation

Wiesinger et al. combine SORT-seq analysis with trajectory inference to reconstruct lineage decisions of sinoatrial node–like cardiomyocytes (derived from induced pluripotent stem cells). WNT and TGFb signaling seem to play a role in these lineage decisions, the authors find.

Journal of Tissue Engineering October, 2022 by Jiuru Li et al.
Molecular and electrophysiological evaluation of human cardiomyocyte subtypes to facilitate generation of composite cardiac models

The authors directed the differentiation of human induced pluripotent stem cells to three types of heart cell: sinoatrial nodal, atrial and ventricular cardyomyocytes. SORT-seq established that the protocols indeed yielded distinct cell populations in line with expected identities. Such models can progress the use of cardiomyocytes in drug development.

Clinical & Translational Immunology September, 2022 by Lisanne Lutter et al.
Human regulatory T cells locally differentiate and are functionally heterogeneous within the inflamed arthritic joint

The authors combined SORT-seq and T cell receptor sequencing to investigate the heterogeneity of regulatory T cells (Tregs) derived from synovial fluid of three patients with juvenile idiopathic arthritis. Results indicate Tregs differentiate to classical effector Tregs or GRP56+CD161+CXCL13+ Tregs. They also found novel predicted drivers of local Treg differentiation.

Science September, 2022 by Samuel J. Wattrus et al.
Quality assurance of hematopoietic stem cells by macrophages determines stem cell clonality

Wattrus et al. establish that hematopoietic stem and progenitor cells (HSPC) are quality assured for stress levels during development. Calreticulin is revealed as an “eat-me” molecule that initiates macrophage-HSPC interaction and leads to programmed cell clearance or stem cell expansion. They used SORT-seq to characterize the macrophage and HSPC subpopulations involved.

JCI Insight September, 2022 by Viviana Valeri et al.
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.

Cardiovascular Research September, 2022 by Monika M. Gladka et al.
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.

Immunity September, 2022 by Pascal Chappert et al.
Human anti-smallpox long-lived memory B cells are defined by dynamic interactions in the splenic niche and long-lasting germinal center imprinting

Immune memory in humans has been shown to extend well beyond decades. Using SORT-seq, Chappert et al. elucidate an extensive functional characterization of human splenic smallpox/vaccinia protein B5-specific memory B cells generated more than 40 years ago. This can be used to decipher the distinct selection and survival mechanisms associated with their longevity.

Science Advances August, 2022 by Celine Souilhol et al.
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.

Development August, 2022 by Erik J. Vrij et al.
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.

Cell Reports July, 2022 by Lieke L. van de Haar et al.
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.

Nature Biotechnology July, 2022 by Johanna F. Dekkers et al.
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.

Journal of Allergy and Clinical Immunology June, 2022 by Leo Laoubi et al.
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.