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Muzlifah Haniffa is a dermatologist working at Newcastle University and Wellcome Sanger Institute. Her achievements were recognized by the 2019 Foulkes Foundation Medal awarded by the Academy of Medical Sciences. She also plays a pioneering role in the Human Cell Atlas initiative.

Important biological questions can be addressed by interrogating the transcriptomes of cancer cells. In a recently published landmark study, Giustacchini and collaborators used a single-cell approach to analyse mRNA of cancer cells derived from patients with chronic myeloid leukaemia. Herein, we discuss how this approach could be used to address relevant clinical questions.

Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

Single-cell transcriptomic and phylogenetic analyses reveal new insights into the developmental origin and potential therapeutic targets for a particularly aggressive form of B-cell acute lymphoblastic leukemia in infants.

A single-cell atlas of human fetal bone marrow in healthy fetuses and fetuses with Down syndrome provides insight into developmental haematopoiesis in humans and the transcription and functional differences that occur in Down syndrome.

Although single-cell RNA sequencing analysis now allows simultaneous examination of transcriptome and T cell receptor repertoire sequences, integrating these two modalities remains a challenge. Here, the authors develop mvTCR, a generative deep learning model that integrates transcriptome and T cell receptor data into a joint representation capturing cell functions and phenotypes.

The diversity of human mononuclear phagocyte subsets remains to be characterized in many tissue-specific and functional contexts, including pulmonary inflammation. Here the authors characterize dendritic cell and monocyte subset recruitment to the bronchoalveolar space in a human LPS inhalation model.

Transcriptomes of about 70,000 single cells from first-trimester deciduas and placentas reveal subsets of perivascular, stromal and natural killer cells in the decidua, with distinct immunomodulatory profiles that regulate the environment necessary for successful placentation.

A comprehensive multi-omics reference atlas of prenatal human skin shows that innate immune cells crosstalk with non-immune cells to perform pivotal roles in skin morphogenesis, including the formation of hair follicles.

The transcription factors TCF1 and LEF1 promote self-renewal and regulatory functions in B-1a cells.

Haniffa and colleagues provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for cutaneous T cell lymphoma.

This study provides a comprehensive spatiotemporal map of human and mouse gonadal differentiation, using a combination of single-cell and spatial transcriptomics, chromatin accessibility assays and fluorescent microscopy, which can guide in vitro gonadogenesis.

A quantitative morphological framework for the human thymus reveals the establishment of the lobular cytokine network, canonical thymocyte trajectories and thymic epithelial cell distributions in fetal and paediatric thymic development.

This Perspective outlines the Human Developmental Cell Atlas initiative, which uses state-of-the-art technologies to map and model human development across gestation, and discusses the early milestones that have been achieved.

Single-cell transcriptomic profiling of fetal liver, skin, kidney and yolk sac reveals the differentiation trajectories of human haematopoietic stem cells and multipotent progenitors, which are validated to produce an integrated map of fetal liver haematopoiesis.

A multiomic atlas of human embryonic joint and cranium development enables detailed analysis of bone and cartilage maturation.

The study provides a comprehensive transcriptomic atlas of the human gastrointestinal tract across the lifespan, highlighting inflammation-induced changes in epithelial stem cells that alter mucosal architecture and promote further inflammation.

Interleukin 26 (IL-26) has been shown to have antimicrobial and pro-inflammatory effects. Here the authors establish a role for IL-26 in the generation of IL-17A producing Th17 CD4⁺ T cells and suggest it involves epithelial cross talk in skin lesions of psoriasis patients.

Bacterial products in the gut–liver axis and tissue stromal factors can tune liver immunity by driving myeloid instruction of CD8⁺ T cells with immunomodulatory ability.

A human SARS-CoV-2 challenge study in individuals without previous exposure to the virus or vaccines provides detailed profiles of local and systemic epithelial and immune cell response dynamics over time and infection status.

Mechanisms explaining the milder clinical syndrome that is observed in children with SARS-CoV-2 infection.

Cells from embryonic, fetal, paediatric and adult human intestinal tissue are analysed at different locations along the intestinal tract to construct a single-cell atlas of the developing and adult human intestinal tract, encompassing all cell lineages.

Cutaneous T cell lymphomas (CTCL) are still poorly characterised at the molecular and single-cell level. Here, the authors analyse CTCL patient samples using single-cell RNA-seq, TCR and whole-exome sequencing, revealing the molecular profiles of malignant T cells and their association with the microenvironment and clinical outcomes.

Phylogenies of human placental cells based on whole-genome sequencing of bulk samples and microdissections reveal extensive mutagenesis in placental tissue, and suggest that mosaicism is a typical part of normal placental development.

In vivo developmental atlases provide a crucial reference for the new class of stem-cell-derived human embryo models, helping accelerate insights into the mechanisms of human development.

Steele et al. use single-cell RNA sequencing and spatial transcriptomics to provide an atlas of adult human skin fibroblasts in healthy and diseased human skin.

Composition and function of immune populations at barrier surfaces is crucial for response to infection. Here, the authors identify a population of dendritic cells in human epidermis, abundant in anogenital epithelia and distinct from Langerhans cells by surface phenotype and by high capacity for HIV infection and transmission.

Comparison of transcriptomic data from immune-stimulated cells across different species sheds light on the architecture of the innate immune response.

A computational pipeline enables differential V(D)J usage analysis and pseudotime trajectory inference from single-cell AIR sequencing.

Pallett et al. report that myeloid derived suppressor cells expand, home to the liver, and inhibit T cell-mediated liver damage in chronic hepatitis B virus infection.

Wesley et al. describe the developmental trajectories of human foetal liver cell types at single-cell resolution and generate bipotential hepatoblast organoids, which can serve as a new platform to investigate human liver development.

Much insight into the workings of the immune system has been garnered from studying patients with primary immunodeficiencies. This article describes the recent discovery of human dendritic cell deficiencies and explains the lessons we can learn from these syndromes.

Transcriptomic analysis may provide information about the differentiation state and cell of origin of a cancer. Here, the authors assess mRNA signals in 1300 childhood and adult renal tumors and report a fetal origin of childhood tumors and no dedifferentiation of adult tumors.

Epithelial tissue mononuclear phagocytes (MNP) can transmit HIV to CD4 T cells, but less is known about sub-epithelial cells. Here, the authors describe MNPs in human anogenital and colorectal tissues and find that CD14⁺CD1c⁺ monocyte-derived dendritic cells and langerin-expressing conventional dendritic cells 2 preferentially take up and transmit HIV.

The innate immune response in epithelial cells after SARS-CoV-2 infection is not fully understood. Here the authors use human air-liquid interface culture and show single cell transcription changes and delayed type I Interferon responses after SARS-CoV-2 infection compared with other respiratory viruses.

Evidence of protective and homeostatic roles for IgE is relatively limited. Strid and colleagues demonstrate that γδ T cells induce switching to IgE that provides protection against experimentally induced epithelial cancer.

Research software engineering is central to data-driven biomedical research, but its role is often undervalued and poorly understood.

Single-cell multi-omic profiling has revealed how the immune system is established in the human embryo, mapping in unprecedented detail the emergence of progenitors, the handover of haematopoiesis between sites and the diversification of cell lineages across the body.

Single-cell technologies have unveiled a complex understanding of NK cells that has led to variations in nomenclature and inconsistencies across the scientific literature. Here, Vivier and colleagues used these technologies to dissect the heterogeneity of NK cells, revealing three prominent NK cell subsets in healthy human blood.

GASPACHO is a statistical method that identifies nonlinear dynamic genetic effects using single-cell RNA-seq data. Analysis of an antiviral response in human fibroblasts identifies 1,275 expression QTLs, many of which colocalize with risk loci for autoimmune and infectious diseases.

The Human Cell Atlas (HCA) aims to characterize cells from diverse individuals across the globe to better understand human biology. Here, the authors lay out principles and action items that have been adopted to affirm HCA’s commitment to equity so that the atlas is beneficial to all of humanity.

Diversity is a creative force that broadens views and enhances ideas; it increases productivity as well as the impact of our science, making our respective organisations more agile and timely. Equality of opportunity is a key to success for any research organisation. Here we argue that every research organisation, whether in academia or in industry, needs to have better inclusion policies to harness the benefits of diversity in research. Drawing from our personal experiences and perspectives as women in science, we share our suggestions on how to promote inclusion in academia and create a better research culture for all. Our shared experiences highlight the many hurdles women in science face on a daily basis. We stress that rules and regulations, as well as education for awareness, will play critical role in this much needed shift from a male-dominated scientific culture that dates from Victorian times to a modern focus on gender equality in science. The key ingredients of this new culture will be flexibility, transparency, fairness and thoughtfulness.

Prenatal immune suppression is regulated by fetal arginase-2-expressing dendritic cells which respond normally to toll-like receptor stimulation but, in contrast to adult dendritic cells, induce regulatory T cells and repress TNF-α secretion by effector T cells.

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 and poor outcomes. Here the authors compare the transcriptomes of single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in these patients.

This Resource describes data, code and tools developed for the Human Reference Atlas and the Human BioMolecular Atlas Program for building and navigating a multiscale human atlas.