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Transition paths by which embryonic stem cells commit to different lineages are not well understood. Here, the authors use combined lineage plus 37-dimensional protein information to identify a developmental cell population co-expressing Sox1 and FoxA2.

Using single-cell profiling of Nanog and Oct4 protein levels in mouse embryonic stem cells, Schroeder and colleagues show that differences in Nanog levels are not correlated with differences in expression of other pluripotency factors and cell fate.

Therapeutic application of hematopoietic stem cells requires a thorough understanding of their in situ differentiation pathways. Here they use single cell proteo-transcriptomic sequencing to identify human HSPC differentiation cues and an immunoregulatory function of CD273/PD-L2 on early HSPCs.

Live imaging and single-cell analyses are used to show that decision-making by differentiating haematopoietic stem cells between the megakaryocytic–erythroid and granulocytic–monocytic lineages is not initiated by stochastic switching between the lineage-specific transcription factors PU.1 and GATA1, which challenges the previous model of early myeloid lineage choice.

We know that variations in cell cycle duration between cells naturally occur but the mechanisms are largely unknown. Here, using lineage tracking, hierarchical clustering and Monte Carlo methods, the authors show that large differences in granddaughter cell cycle duration are driven by asymmetric divisions.

Passegué and colleagues reveal that pro-inflammatory IL-1 accelerates cell division and induces PU.1-mediated differentiation of HSCs into myeloid cells, whereas chronic IL-1 exposure compromises HSC function.

Prospective isolation of defined cell types is a crucial prerequisite for their molecular analysis, but the heterogeneity of populations yielded by current protocols obscures relevant information. New studies now use additional features from time-resolved imaging data for live prospective identification of cells with defined future behavior.

Multipotent stem and progenitor cells are heterogeneous in lineage choice and timing of commitment to differentiation.

Liquid handling and pipetting tools can automate repetitive tasks but are far from universally used. Here the authors report the Pipetting Helper Imaging Lid (PHIL), an open-source liquid handling robot designed for inexperienced users, that they use for automated pipetting.

The timing of cell fate choices is usually unknown, because we have to rely on indirect evidence of their molecular basis. Here, the authors introduce a method to infer decision times from marker onset in cell genealogies, and find evidence refuting the paradigmatic PU.1/GATA1 cell fate switch.

Recent studies have indicated that embryonic blood is produced by endothelial cells, which also form blood vessels and arteries. This paper uses a direct imaging and cell tracking approach to directly show that embryonic endothelial cells do produce blood. By imaging cells over days, they were able to show that a subset of embryonic endothelial cells formed blood cells.

Haematopoietic stem cells emerge from the haemogenic endothelium via an endothelial-to-haematopoietic transition. Here, the authors show using single cell functional and transcriptional analyses that haemogenic endothelial cells begin to lose their endothelial potential while still located within the haemogenic endothelium.

Accurate quantification of bioimaging data is often confounded by uneven illumination (shading) in space and background variation in time. Here the authors present BaSiC, a Fiji plugin solving both issues. It requires fewer input images and is more robust to artefacts than existing shading correction tools.

Schroeder and colleagues review the development and application of single-cell technologies — from gene and protein expression to clonal labelling, lineage tracing and time-lapse imaging — in stem cell research.

This resource paper describes the steps involved in carrying out quantitative multicolour imaging in tissue. It is applied to cleared mouse bone and plots the spatial distribution of specific cell populations within the marrow.

The cellular degradative machinery can be asymmetrically inherited upon haematopoietic-stem-cell division, which predicts the future metabolic and translational activation of their daughter cells.

A dual genetic strategy enables the labelling and in vivo imaging of native long-term haematopoietic stem cells in the mouse calvarial bone marrow.

The Myc transcription factor is a major regulator of stem cell (SC) self-renewal and pluripotency but how this integrates signals from other pathways is unclear. Here, the authors show that Myc activation triggers epigenetic memory in self renewing embryonic SCs via PRC2-mediated potentiation of the Wnt pathway.

MicroRNAs regulate haematopoietic stem cell (HSC) development to ensure the correct generation of blood cells. Haetscher et al. show in mice that miR-193b controls the life-long self-renewal ability of HSCs via AKT and STAT5 pathways, with loss of miR-193b accelerating HSC expansion and reducing differentiation.

A deep learning approach enables fast and robust prediction of hematopoietic stem cell lineage choice in time-lapse imaging three generations before conventional marker onset.

Adult mouse subependymal neural stem cells (aNSCs) give rise to neuronal and oligodendroglial progeny. Berninger and colleagues use continuous live imaging and single-cell tracking to demonstrate that single aNSCs isolated from the mouse brain generate exclusively either oligodendrocytes or neurons. They also show that Wnt activation stimulates oligodendrogenic progenitor proliferation without affecting neurogenic clones.

A compendium detailing the localization of bone and bone-marrow-microenvironment cells and proteins will enable efforts to understand the functions of this niche.

The experimental and computational tools that enable continuous imaging of single cells for days and weeks have advanced rapidly in recent years, and solutions to current limitations are on the horizon.

Here, DNA damage is shown to occur as a direct consequence of inducing haematopoietic stem cells to exit quiescence in response to conditions of stress; in mice with mutations modelling those seen in Fanconi anaemia, this leads to a complete collapse of the haematopoietic system.