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.
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.
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.
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.
Inflammatory response in hematopoietic stem and progenitor cells triggered by activating SHP2 mutations evokes blood defects
Hematopoietic stem and progenitor cells (HSPCs) are the disease-propagating cells of juvenile myelomonocytic leukemia (JMML). A SHP2 mutation is common in these patients, and Solman et al. reproduced it in zebrafish. Single-cell mRNA sequencing of HSPCs from mutant zebrafish embryos and bulk sequencing of HSPCs from JMML patients revealed an overlapping inflammatory gene expression pattern. Pharmacological inhibition of the inflammatory response positively impacted mutant zebrafish, suggesting therapeutic possibilities in JMML patients.
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.