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Age-associated decline in tissue function has been linked to alterations in adult stem cells, with implications for organ homeostasis and cellular therapy. Here, the authors study the heterogeneity of ageing mouse haematopoietic stem cells (HSCs) and find that the compromised blood cell-forming potential of individual and functionally defined aged HSCs can be reset by reprogramming.

Human embryonic stem cell cultures are morphologically heterogeneous. Here, differences in Wnt signalling are shown to contribute to this heterogeneity, cells containing high levels of Wnt form endodermal and cardiac cells, whereas cells with low Wnt form neuroectodermal cells, when differentiation is induced.

Does blood formation in mammalian embryos and adults have separate origins or a common source? The most recent investigations into the question add a further chapter to this long-running story.

An analysis of skeletal stem cells in mice reveals that bone ageing occurs at the level of local niches affecting skeletal and haematopoietic lineage output, which may influence systemic aspects of multi-organ physiological ageing.

CRISPR-mediated gene knockout and activation are used to identify molecules in cancer cells and macrophages that regulate antibody-dependent cancer cell phagocytosis.

In aged mice, inhibition of prostaglandin E₂ (PGE₂) signalling through its receptor EP2 improves cellular bioenergetics, reduces inflammatory responses and restores hippocampal plasticity to youthful levels, resulting in an improvement in spatial memory and cognition.

The combination of anti-GD2 and CD47 blockade mediates robust anti-tumor activity in mouse models of neuroblastoma, osteosarcoma and small-cell lung cancer by reorienting macrophage activity toward tumor cell phagocytosis.

Expression profiling on 75,000 single cells creates a comprehensive cell atlas of the human lung that includes 41 out of 45 previously known cell types and 14 new ones.

SIRPa is most commonly known as a phagocytosis inhibitory receptor expressed by myeloid cells. Here the authors show SIRPa is expressed on a subset of CD8+ T cells with higher proliferative and effector activity during the chronic phase of the immune response to viral infection.

Antibodies against Plasmodium falciparum glutamic-acid-rich protein (PfGARP), an antigen expressed on the surface of infected red blood cells, kill P. falciparum parasites by inducing programmed cell death and reduce the risk of severe malaria.

Group 3 medulloblastoma is an aggressive pediatric brain tumour that disseminates through the leptomeningeal cerebral spinal fluid. Here, the authors show that in Group 3 medulloblastoma NOTCH1 activates BMI1 through the activation of TWIST1, driving metastasis and self-renewal, and in mouse models a NOTCH1 blocking antibody decreased spinal metastases.

Single-walled carbon nanotubes can restore phagocytotic properties of macrophages in artherosclerotic plaques to promote plaque clearance and combat artherosclerosis.

Eight genome-wide CRISPR screens identify genes required for substrate-specific phagocytosis. The study highlights roles for NHLRC2 in filopodia formation, very-long-chain fatty acids in substrate-specific phagocytosis and TM2D3 in uptake of amyloid-β aggregates.

Single-cell transcriptomic analysis of neurogenic niches in young and old mice reveals that T cells infiltrate the neurogenic niches of old mice and inhibit the proliferation of neural stem cells, in part through expression of interferon-γ.

Heterogeneity within populations of stem cells, cancer cells or other cell types of interest presents a formidable barrier to analysis. Lu et al. use viral barcoding and high-throughput sequencing to track the differentiation of single hematopoietic stem cells in vivo.

Prevailing models propose that coronary arteries in the developing heart are formed from progenitor cells originating in the proepicardium. It is found here, however, that these arteries arise from angiogenic sprouts of the major vein that returns circulating blood to the embryonic heart. Thus some differentiated venous cells retain developmental plasticity and respond to local signals to convert to coronary arteries, capillaries and veins.

The adult mammalian cochlear sensory epithelium consists of mechanosensory hair cells and supporting cells but hair cells cannot regenerate. Here, the authors identify multipotent progenitors that arise fromEya1-expressing otic cells that can regenerate hair cells in mice after 1 week of age.

Pathways dependent on the transcription factor NF-κB provide innate immunity against microbes. Karin and colleagues show that mice lacking the kinase IKKβ have IL-1-dependent neutrophilia. Loss of IL-1 signaling restores blood cellularity but severely compromises antimicrobial defense.

Super-enhancers (SEs) are big DNA regions regulating the transcription of oncogenes. Here the authors identify two SE regions regulating the expression of CD47, a protein expressed by cancer cells to avoid phagocytosis by macrophages, thus suggesting a potential mechanism of immune surveillance escape.

Dysfunction of the gastrointestinal system, and to the autophagy lysososmal pathway (ALP) have been reported in Parkinson’s disease. Here the authors report epigenetic disruption of ALP related genes in the appendix of individuals with Parkinson’s disease.

During development, new arteries can arise from pre-existing veins; the cell fate switch involved occurs gradually and before the onset of blood flow in mouse embryo hearts.

Drukker and colleagues differentiated human embryonic stem (ES) cells for 3 days and screened the cells for labeling by >400 antibodies. They identified cell-surface markers expressed on four classes of early progenitor cell.

CD24 interacts with the tumour-associated-macrophage receptor Siglec-10 to inhibit the macrophage-mediated clearance of cancer cells, revealing a new ‘don’t eat me’ signal as a potential target for cancer immunotherapy.

Endocrinologists have traditionally focused on studying one hormone or organ system at a time. Here the authors use transcriptomic data from the mouse lemur to globally characterize primate hormonal signaling, describing hormone sources and targets, identifying conserved and primate specific regulation, and elucidating principles of the network.

A transcriptomics study demonstrates cell-type-specific responses to differentially aged blood and shows young blood to have restorative and rejuvenating effects that may be invoked through enhanced mitochondrial function.

Circular extrachromosomal DNA in high-risk medulloblastoma contributes to tumor heterogeneity and associates with relapse and survival. Enhancer rewiring events involving known oncogenes are frequent events, affecting transcription and proliferation.

A single-cell transcriptomic atlas across the lifespan of the mouse, denoted Tabula Muris Senis, provides molecular information about the hallmarks of ageing in a range of tissues and cell types.

In this work, the neural crest stem cell marker CD271 is implicated as a cancer stem cell marker, allowing identification and prospective isolation of melanoma cancer stem cells.

Research on embryonic stem cells holds huge promise for understanding and treating disease. Many people oppose such research on religious and ethical grounds, but two new methods may bypass some of these objections.

An adversarial domain translation framework is presented for scalable integration of single-cell atlases across samples, technical platforms, data modalities and species.

Mitochondrial DNA mutations in iPSCs can render them immunogenic.

Endogenous skeletal stem cells are recruited to form cartilage in mice when stimulated by microfracture surgery together with localized delivery of growth factors, pointing to a new approach for treating cartilage defects.

Bulk RNA sequencing of organs and plasma proteomics at different ages across the mouse lifespan is integrated with data from the Tabula Muris Senis, a transcriptomic atlas of ageing mouse tissues, to describe organ-specific changes in gene expression during ageing.

A ‘mouse atlas’, comprising single-cell transcriptomic data from more than 100,000 cells from 20 organs and tissues, has been created as a resource for cell biology.

Single-cell transcriptomic data from a neurogenic region of the mouse brain were used to build aging clocks for specific neural cell types. These clocks showed that heterochronic parabiosis and exercise lead to distinct transcriptomic rejuvenation patterns across cell types.

Stem cells have traditionally been characterized as either embryonic (pluripotent) or organ-specific. Recent work suggests that the latter can "transdifferentiate" into other cell types, carrying significant implications for possible clinical use of these cells. Here the authors critically examine the existing data, and suggest standards for the evaluation of these and future studies.

Despite a decade of intensive preclinical research, the translation of cancer nanomedicine to the clinic has been slow. Here, we discuss how recent lessons learned from the successes with immuno-oncology therapies could be applied to cancer nanomedicine and how this may help to overcome some of the key technical challenges in this field.

Normalization of the tumour vasculature can improve immune effector cell infiltration, leading to immunotherapy potentiation. In this Opinion article, Huanget al. propose that reciprocal regulation between tumour vascular normalization and immune reprogramming forms a positive feedback loop that can induce durable antitumour immunity within the tumour microenvironment.

Using cells derived from human pluripotent stem cells for therapeutic applications carries a risk that rare undifferentiated cells in the transplant will give rise to teratomas. Tang et al. identify a new antigen on the surface of human pluripotent cells that, combined with other antigens, enables complete depletion of teratoma-initiating cells.