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The role of autoantibodies in bullous pemphigoid (BP) and their impact on keratinocytes and the response to BP pathology remains underexplored. By leveraging transcriptomics analysis and large-scale protein assays, here the authors identify keratinocyte MyD88 as a regulator of the pro-inflammatory response in BP, uncovering the role of keratinocytes in this disease pathology.

Microbiome composition is influenced by genetics, although the specific host genetic factors responsible are not well known. Here, the authors performed a genome-wide meta-analysis to discover host genetic effects on skin microbiota and finding potential causal effects of microbiota composition on skin diseases.

In a large cross-national study, education was linked to better memory and larger brain volumes but not to slower cognitive or brain decline with age, suggesting that the association reflects early-life factors rather than neuroprotective effects in aging.

During the progression of cutaneous squamous cell carcinoma (cSCC), dermal fibroblasts become activated into cancer-associated fibroblasts (CAFs) which are pro-tumorigenic. Here, using single-cell RNA sequencing of patients’ samples at different stages of cSCC progression, the authors identify two main CAF subsets and deduce their potential functions using bioinformatics.

Invariant natural killer T (iNKT) cells are tissue-resident immune cells recognizing lipid antigens. Here the authors find that liver, but not lung nor spleen, iNKT cells alter their transcriptome upon systemic treatment of lipid nanoparticles for the induction of regulatory B cells and suppression of liver and pancreas autoimmunity in mouse models.

A challenging problem is to identify the most central agents in interconnected multilayer networks. Here, De Domenico et al. present a mathematical framework to calculate centrality in such networks—versatility—and rank nodes accordingly.

The failure of chemotherapy in colorectal cancer is currently unclear. Here, the authors show that upon sub-lethal dose of chemotherapy wild-type p53 colorectal cancers acquire a quiescence-like phenotype and a YAP-dependent fetal-like intestinal stem cell state associated with a higher metastatic activity and poor prognosis in patients.

Understanding the immunological underpinnings of long-term survival in cancer is of high interest. Here, authors dissect the immune parameters of multiple myeloma long-term survivors following a single line of therapy longitudinally, and find sustained changes, including inflammation and impaired immune function.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

DNA demethylation is known to be critical for the development and function of many tissues. Here the authors show that it is also required for intestinal lineage differentiation, and that mice lacking DNA demethylases have altered microbiomes and a predisposition to inflammation.

Recombinant MHC class II molecules are instrumental in antigen-specific T-cell identification assays and showed efficacy as experimental medicines. Here, the authors engineer MHC class II molecules with species-specific knob-into-hole heteromerization domains, enabling a translatable purification process with improved stability, yields, and biological potency.

Genome-wide analyses using fetal and parental genotypes identify 40 independent associations influencing placental weight and highlight the role of the fetus in preeclampsia risk and placental growth regulation via insulin signaling.

The hematopoiesis of patients with del(5q) Myelodysplastic Syndromes is composed of a mixture of cells with and without the deletion. Here, the authors show that del(5q) and non-del(5q) cells share similar transcriptional alterations, with del(5q) cells presenting additional lesions. Moreover, hematological response to lenalidomide is associated with the reversal of some transcriptional lesions in both del(5q) and non-del(5q) cells.

Barbosa, Stein et al. show that rather than operating independently, PFC persistent activity and ‘activity-silent’ mechanisms interact dynamically to produce serial effects in working memory, consistent with attractor models with synaptic plasticity.

Nanoparticles can be used as ligand-multimerization platforms to activate specific cellular receptors in vivo.

Fjell et al. analysed multiple large-scale longitudinal MRI datasets and found no evidence for an association of sleep duration and brain atrophy, suggesting that normal brains promote adequate sleep.

Auxin is a key regulator in vascular cambium development. This study shows that gibberellins promote polar auxin transport along the root, which leads to broadening of high auxin signalling domain in cambium, and thus, to increased xylem formation.

The spatial architecture of multiple myeloma remains to be explored. Here, the authors perform bulk and single cell sequencing for samples from newly diagnosed patients and reveal gene signatures associated with focal lesions and spatial heterogeneity in the tumour microenvironment.

Tooth shapes vary greatly amongst mammals, but the genetic underpinnings and functional relevance of new dental morphologies are largely unknown. Gomes Rodrigues et al. show that Eda and Edargenes modulate molar crest development in mice, enabling incipient adaptation to highly fibrous diets.

Avgustinova et al. report that targeting the H3K9 methyltransferase G9a in skin cancer does not affect single nucleotide variant profiles, but leads to increased tumour aggressiveness after a prolonged latency.

The flow of ice streams leaves traces in the stratigraphy of the ice sheets. Made visible by radar, they reveal the history of the upper North East Greenland Ice Stream. The ice stream is found to have existed in its current form for only about the last 2000 years.

Multidrug resistance of the opportunistic pathogen Stenotrophomonas maltophilia is an increasing problem. Here, analyzing strains from 22 countries, the authors show that the S. maltophilia complex is divided into 23 monophyletic lineages and find evidence for intra-hospital transmission.

Using cervical explant models and cervical tissue from ART-suppressed HIV⁺ women, the authors here show that resident memory T cells (T_RM) in the cervical mucosa are preferentially infected and harbor more viral DNA, RNA and protein than non-T_RM, suggesting that T_RM may serve as viral reservoir in the cervical mucosa.

Azacitidine (AZA) treatment is used for patients with myelodysplasias that cannot undergo bone marrow transplantation; however, AZA treatment is only partially effective. Here the authors show synergy of AZA with compounds inhibiting the chromatin regulators CBP and p300, which is mediated by the RNA-dependent functions of AZA affecting protein translation.

The phylogenetic and biogeographic origin of Perissodactyla (horses, rhinoceroses and tapirs) is unclear. Here the authors report 54.5 Myr fossils from a sister taxa of Perissodactyla found in India, which suggests that the group may have originated in India before its collision with Asia.

Biocrusts reduce global atmospheric dust emission by 60%, and future biocrust losses due to climate and land-use changes will exacerbate this effect, according to global models of dust cycling.

Solé-Boldo et al characterise dermal fibroblasts in human skin not exposed to sunlight by single-cell RNA sequencing. They identify fibroblast subpopulations and see that aging reduces their identity and predicted interactions with other skin cells, providing insights into age-related changes in skin.

In this issue of Nature Genetics, Lara-Astiaso et al. systematically characterized the functional roles of several chromatin factors in hematopoiesis by combining functional CRISPR screens with single-cell transcriptomics and chromatin accessibility profiling, revealing lineage biases and relationships with important transcription factors.

In intestinal adenomas carrying active β-catenin, Jagged1 (Jag1) ligand is responsible for Notch1 activation. Here, the authors show the reliance of Notch on Jag1 in cancer, and investigate how Jag1–Notch1 signaling interference may provide therapeutic benefits in some colorectal cancer patients

5.33 million years ago, in an event known as the Zanclean flood, Atlantic waters refilled a mostly desiccated Mediterranean Sea which had become disconnected from the world's oceans; however, the nature, abruptness and evolution of this flood remain poorly constrained. Using borehole and seismic data and a model study, it is now suggested that 90 per cent of the water was transferred in a short period of a few months to two years, with peak rates of sea level rise in the Mediterranean possibly reaching more than 10 metres per day.