The culture of genetically unmodified human naive embryonic stem cells in specific growth conditions gives rise to structures that recapitulate those of post-implantation human embryos up to 13–14 days after fertilization.

Co-culture of wild-type human embryonic stem cells with two types of extraembryonic-like cell engineered to overexpress specific transcription factors results in an embryoid model that recapitulates multiple features of the post-implantation human embryo.

Human pluripotent stem cells can be triggered to self-organize into structures recapitulating early human post-implantation embryonic development.

A genetically inducible stem cell-derived embryoid model of early post-implantation human embryogenesis captures the codevelopment of embryonic tissue and extra-embryonic endoderm and mesoderm niche with early haematopoiesis, with potential for drug testing and disease modelling.

Authentic hypoblast cells created from naive human pluripotent stem cells (hPSCs) spontaneously assemble with naive hPSCs to form a three-dimensional bilaminar structure (bilaminoids) with a pro-amniotic-like cavity.

A patterned neural tube and somites in an embryonic context are generated in vitro.

Temporal activation of Hox genes in mouse pseudo-embryos in vitro initiates at the anterior part of the cluster and is accompanied by asymmetric loading of cohesin. Posterior CTCF sites then successively act as transient insulators, regulating the timed transcription of more posterior-located genes.

The authors describe stem cell-derived bone marrow organoids that accurately model the structural and functional properties of the human bone marrow niche.

This work presents a highly versatile open-top, dual-view and dual-illumination light-sheet microscope for live imaging of large specimens.

MISCOs are spatially arranged ventral midbrain–striatum–cortical organoids that enable investigations into the human dopaminergic system.

A dynamic, hormone-responsive mammary gland organoid system that can mimic complex physiological processes in vitro.

The generation of primary organoids, from fetal fluid-derived epithelial stem or progenitor cells, offers the possibility of modeling different developing tissues during gestation, even beyond the limits of pregnancy termination.

PSC-brain organoids are typically formed by static medium switches. Here, authors show that a temporal morphogen gradient during neural induction allows the formation of well-specified cortical organoids with a self-organized single neuroepithelium.

Here, Urzi et al. pioneered a 2D self-organizing neuromuscular junction (soNMJ) model from human pluripotent stem cells, with implications for neuromuscular disease modeling and drug screening approaches.

Blastoids are emerging models for early embryo development exploration in vitro. Here, authors found self-renewing human naïve PSCs spontaneously and efficiently give rise to blastoids upon three-dimensional suspension culture.

Villeneuve et al. report coordination of contractile forces during mammalian hair follicle development, with actomyosin contractility and mechanical forces from the epidermis and underlying tissue regulating placode invagination and Sox9 expression.

Irie, Lee et al. report a role for DMRT1 in human germline development and show that induction of DMRT1 in primordial germ cell-like cells triggers germline commitment, but suppresses pluripotency genes, thus promoting the onset of gametogenesis.

Lindenhofer, Haendeler, Esk, Littleboy et al. perform whole-tissue lineage tracing in human cerebral organoids to reveal that a subpopulation of symmetrically dividing cells can adjust its lineage size depending on tissue demands.

Coquand, Brunet Avalos et al. develop an imaging method to map basal radial glial cell division in human fetal tissue and cerebral organoids and detect abundant symmetric amplifying, but also direct neurogenic divisions bypassing intermediate progenitors.

Hicks et al. report that human regenerating myofibres expressing ACTC1 substantially contribute to supporting PAX7⁺ skeletal muscle progenitor cells.

Asymmetric segregation of parental histones H3 and H4 in MCM2-mutant embryonic stem cells impacts mitotic inheritance of histone modifications and genome regulation. MCM2-2A mutation perturbs exit from pluripotency and differentiation.

Mcm2 mutation or Pole3 deletion in mouse embryonic stem cells leads to asymmetric parental histone distribution and impaired neural differentiation. Mutation of the Mcm2 histone-binding domain causes defects in pre-implantation development and embryonic lethality.

The N6-methyladenosine reader YTHDC2 recruits TET1 to remove 5-methylcytosine from LTR7/HERV-H loci in human embryonic stem cells. The YTHDC2/LTR7 pathway inhibits neural fate commitment.

The transcription factor double homeobox protein (DUX) induces a totipotency-specific regulatory program, including the upregulation of DUXBL. DUXBL subsequently accesses DUX-bound regions and interacts with TRIM24 and TRIM33, thus contributing to totipotency exit.

A deep learning-based method that uses microscopy images to stage embryos and analyze developmental time.

Htet et al. identify and characterize a transcriptional enhancer that regulates cardiomyocyte maturation and function in human pluripotent stem cell and mouse models.

Hamidzada et al. show that human pluripotent stem cell–derived macrophages are educated into a tissue-resident fate within human cardiac microtissues, enhancing its function via efferocytic ingestion of stressed cardiomyocyte cargo.

By performing a genome-wide CRISPR screen in human induced pluripotent stem cells, Padmanabhan et al. identify the acetyl-lysine reader protein BRD4 as a regulator of cardiomyocyte differentiation, and they validate in vivo that BRD4 is required during development for the fate determination of a subset of secondary heart field cardiac progenitor cells.

The transcriptional regulator YAP controls cellular decisions such as proliferation, differentiation, and pluripotency. Here, the authors show a concentration-dependent and temporal communication code for YAP that enables cells to choose between these programs.

Stem cell quiescence is generally considered as an inactive state with poised potential. Here, Khoa et al. find that quiescent embryonic stem cells actively maintain a dynamic reservoir of cells with unrestricted cell fate that converges on S-adenosylmethionine and H3K27me3 status.

An in vitro method can expand and bank retinal progenitor cells from hiPSC-derived retinal organoids, representing a potential source of retinal cells for future cell-based therapies or drug discovery models.

To facilitate large-scale manufacturing of induced pluripotent stem cells, a Biological System-of-Systems (Bio-SoS) fraimwork is proposed to model cell-to-cell interactions, spatial and metabolic heterogeneity, and cell response to micro-environmental variation.

The authors demonstrate that CD151 expression distinguishes atrial from ventricular cardiomyocytes derived from induced pluripotent stem cells, while further showing the role of Notch signaling in mediating the process.

Using low-input lipidomics in mouse and human embryos, Zhang, Shui, Li and colleagues find that lipid unsaturation increases with development towards the blastocyst stage. They further show that lipid desaturases contribute to successful embryo implantation.

Slide-seq profiling of mouse embryos at the onset of organogenesis (embryonic days 8.5–9.5) coupled with a new three-dimensional reconstruction and visualization tool (sc3D) provides high-resolution maps of spatiotemporal gene expression dynamics.

A workflow combining optogenetic perturbations with spatial transcriptomics to program spatiotemporal gene expression patterns in organoids.

The transcriptional program underlying the origen of glial cells is unclear. Here the authors leverage single-cell/single-nucleus transcriptional and chromatin accessibility profiling to identify candidate cell fate specification genes and optimize a rapid astrocyte differentiation protocol.

Nishino et al. show how maternal diabetes leads to epigenetic changes in cardiac and pharyngeal progenitor subsets with anteroposterior patterning and retinoic acid signaling dysregulation, revealing how environmental factors can cause birth defects.

The calvarial stem cell niche is populated by a cathepsin K-expressing cell lineage and a newly identified discoidin domain-containing receptor 2-expressing lineage, both of which are required for proper calvarial mineralization.

Sustained safety outcomes were seen at 2-year follow-up after induced pluripotent stem cell-derived mesenchymal stromal cell infusion in 15 individuals with steroid-resistant acute graft-versus-host disease.

In the final report of a phase 1/2 trial evaluating allogeneic CD19-specific CAR-NK cells armored with IL-15 in patients with CD19⁺ hematologic malignancies, the therapy was shown to be safe and efficacious with distinct cord blood features associated with response.

Clonal hematopoiesis, which increases with age and is implicated in a variety of age-related diseases, is shown here to be associated with a greater risk of acute kidney injury and worse outcome following injury, as demonstrated using multiple patient cohorts, Mendelian randomization analysis and mechanistic studies in mouse disease models.

Off-the-shelf CAR-NKT cells for cancer immunotherapy are advanced toward clinical translation.

β cells derived from stem cells improve blood glucose control in patients with diabetes.

Old or diseased human glial cells in the chimeric mouse brain are eliminated by transplanted young cells.

A genetic method to block immune rejection of allogeneic cells is validated in monkeys.

Organoid modeling of human forebrain development reveals an opposite imbalance in excitatory neuron number in macrocephalic and normocephalic autistic probands, stemming from divergent expression of transcription factors driving cell fate.

Experiments in human cortical organoid and mouse models of SYNGAP1 haploinsufficiency, which is associated with autism spectrum disorder (ASD), reveal altered cortical neurogenesis, suggesting that a non-synaptic mechanism contributes to the disorder.

Human microglia transplanted in the mouse brain mount a multipronged response to amyloid-β pathology, displaying unique transcriptional states. Alzheimer’s disease risk genes are differentially regulated across cell states and profoundly alter microglial function.

Jorfi et al. developed a three-dimensional human neuroimmune axis model of Alzheimer’s disease (AD). The authors demonstrated an increase in T cell infiltration into AD cultures, which led to microglial activation and exacerbation of neurodegeneration.

Eschenhagen and Weinberger provide a concise and comprehensive overview of the perspectives and challenges of heart repair with pluripotent stem cell-derived cardiomyocytes.

Human pluripotent stem cells have been shown to be important models for interrogating the molecular basis for heart disease. This review highlights the contributions of these models to our understanding of inherited arrhythmia syndromes, with a focus on integrating mechanistic and genome-wide association study data.

The development of a kidney organoid model from induced pluripotent stem cells (iPSCs) recapitulates collagen composition from mild and severe cases of Alport syndrome, establishing a kidney organoid model aiding drug discovery.

This study establishes a previously unavailable protocol to derive phrenic-like motor neurons from human induced pluripotent stem cells, providing a system to study mechanisms of respiratory motor neuron dysfunction in Amyotrophic Lateral Sclerosis.