Cardiopedia-Ligand: A ligand-receptor perturbation atlas of human cardiac organoid function and transcriptional state

Hudson and colleagues screen soluble ligands that activate all cell-membrane receptors expressed in multicellular human cardiac organoids. The contractile and transcriptional responses are captured for each individual ligand to generate the foundational Cardiopedia-Ligand dataset. This dataset enables “ligand fingerprinting” of human heart failure samples to prioritize disease drivers.

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Extracellular vesicle secretome from mesenchymal stromal cells prevents post-ischemic heart failure by targeting cardiac fibrosis

Myocardial ischemia-reperfusion injury contributes to heart failure after infarction, yet no therapy directly targets the resulting fibrotic response. Grinnemo and colleagues develop a GMP-compatible extracellular vesicle-based therapy and a positron emission tomography (PET) imaging platform to reduce and monitor myofibroblast activation, establishing a translational framework for personalized treatment.

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Dissecting divergent outcomes in stem cell-derived dopamine cell therapy trials for Parkinson’s disease

Early clinical trials of PSC-derived dopamine cell therapies for Parkinson’s disease show encouraging safety and clinical benefits. However, these trials revealed divergent outcomes. We propose a three-level framework to identify sources of variability across studies, patients, and graft sites within individuals, integrating cell product, host, immune, and transplantation-related factors.

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Reconstructing primate gametogenesis along its developmental trajectory

Using a xenogeneic reconstituted testis transplanted beneath the kidney capsule, Whelan et al. advance human and rhesus macaque pluripotent stem cell-derived germ cells beyond fetal prospermatogonia. Their study highlights developmental time, niche organization, and lineage history as central challenges for reconstructing faithful primate gametogenesis.

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Human iPSC-derived engineered heart tissue model of diastolic dysfunction in heart failure with preserved ejection fraction

Tohyama and colleagues successfully established an in vitro diastolic dysfunction model that mimics HFpEF using hiPSC-derived heart tissues and demonstrated the therapeutic efficacy of SGLT2 inhibitors. Furthermore, they revealed that the restoration of the eNOS-NO-cGMP-PKG signaling pathway in endothelial cells plays a crucial role in ameliorating heart failure.

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Vitamin C attenuates primate bone marrow aging at the molecular and progenitor level

Ye et al. profile primate bone marrow aging across anatomical sites and show that long-term VC supplementation attenuates age-related decline by restoring progranulin-mediated signaling.

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FDA-approved fulvestrant-induced CAR phase separation enables precise control of CAR T antitumor function

Huang et al. engineer a drug-inducible CAR phase-separation (iPhase-CAR) system by coupling an engineered ERα variant with FDA-approved fulvestrant. Fulvestrant drives reversible CAR condensation at the T cell membrane, amplifying tonic signaling in a dose-dependent manner. iPhase-CAR T cells exhibit enhanced antigen sensitivity and programmable antitumor activity both in vitro and in vivo.

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Generation of spermatogonia from human and non-human primate pluripotent stem cells

Sasaki and colleagues generate human and macaque male germ cells up to meiotic onset, including prepachytene piRNA-expressing spermatogonia, from induced pluripotent stem cells. These cells self-organize into seminiferous tubule-like structures and recapitulate the transcriptomic and phenotypic features of their in vivo counterparts.

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From repair to relay: Human retinal organoids re-couple a severed optic nerve

Restoring vision after complete optic nerve transection has long seemed out of reach. In this issue of Cell Stem Cell, Gong et al. now show that human retinal organoids transplanted into the lesion form a chimeric host-graft bridge capable of supporting partial, graft-dependent visual function in adult rats.

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Modeling human hypothalamic cell diversity through developmental patterning

Understanding the cellular diversity of the human hypothalamus has been limited by the lack of accessible models. In this issue of Cell Stem Cell, Abay-Nørgaard et al. demonstrate that temporal control of BMP signaling during hPSC differentiation generates diverse hypothalamic populations, providing a platform to study human hypothalamic development and function.

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Outside the niche: Gut microbiota relay psychological stress to hematopoietic stem cell dysfunction

Hematopoietic stem cells integrate local and systemic cues to sustain blood homeostasis. In this issue of Cell Stem Cell, Tian et al. uncover a stress-responsive brain-gut-bone marrow axis that drives aging-like dysfunction of hematopoietic stem cells.

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Beyond apoptosis: LSC state dictates metabolic and anti-apoptotic vulnerabilities

Two studies published in the last issue of Cell Stem Cell reveal that leukemic stem cell (LSC) identity in acute myeloid leukemia (AML) encodes both anti-apoptotic dependencies and metabolic survival programs. They reframe LSC-directed therapy: eradication may require combinatorial targeting of BCL-2 family proteins and ferroptosis-suppressive ketogenesis in a cell-state-specific manner.

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Long-term lessons from MATCH01 macrophage therapy in cirrhosis

In a long-term follow-up of a phase 1/2 clinical trial, Stuart Forbes and colleagues demonstrate that autologous macrophage therapy improves transplantation-free survival in patients with liver cirrhosis. These findings show the translational value of autologous macrophage-based regenerative therapy for advanced liver diseases.

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From reconstruction to intervention: Engineered organoids as living therapeutic depots

Wang et al. engineer mammary organoids as anticancer drug-secreting depots that inhibit post-surgical tumor recurrence and regenerate functional mammary gland tissue. This work extends the therapeutic utility of organoids beyond tissue reconstruction into living therapeutic depots, establishing a strategy to exploit intrinsic physiological processes of the organoids for therapeutic intervention.

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Human stem cell-based embryo model governance: Insights from Japan

Despite rapid advances in human stem cell-based embryo model (SCBEM) research, national regulatory frameworks remain limited. On April 1, 2026, Japan implemented revised guidelines extending their scope to encompass human SCBEM research. We examine the revisions, differences from ISSCR guidelines, and practical challenges arising during the international regulatory transition period.

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Psychological stress drives aging-like hematopoietic stem cell dysfunction through a brain-gut-bone marrow axis

Zhao and colleagues show that psychological stress impairs hematopoietic stem cell function through a brain-gut-bone marrow axis. Stress-responsive neural circuits remodel the intestinal environment via sympathetic signaling, reducing microbiota-associated spermidine and promoting ferroptotic stress in stem cells, thereby driving aging-like hematopoietic dysfunction.

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Quantitative molecular cartography of emergency myelopoiesis reveals conserved modules of hematopoietic activation

Swann et al. conducted a comparative analysis of single-cell RNA-sequencing data from emergency myelopoiesis models, finding that different perturbations act at distinct levels of the hematopoietic hierarchy. They identified a conserved myeloid progenitor-based transcriptional activation module across multiple disease conditions, which informs outcomes in human acute myeloid leukemia.

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Paired pre- and post-transplant human immunoprofiling identifies an IFN-γ-JAK1 axis limiting stem-cell-derived RPE engraftment

Gao et al. identify a Th1-biased, IFN-γ-rich immune state that reprograms hESC-RPE immunogenicity through JAK1 signaling. Brief ex vivo ruxolitinib conditioning dampens HLA induction and immune infiltration, improving graft survival and visual function in humanized models and supporting ex vivo JAK inhibition as a practical adjunct to RPE cell therapy.

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ENPP1 blockade with a humanized monoclonal antibody enhances renal repair after acute kidney injury

Deb and colleagues identify ENPP1 as a critical negative regulator of kidney regeneration. They demonstrate that targeting ENPP1 using a novel humanized monoclonal antibody enhances tubular cell proliferation and accelerates renal repair in mouse models and non-human primates, offering a potential therapeutic strategy for kidney disease.

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ZNF512B safeguards genome integrity at regulatory regions to repress the SASP and inflammation

Belmonte and colleagues show that ZNF512B safeguards genome integrity by directing DNA repair to key regulatory regions. This mechanism limits inflammatory signaling and the senescence-associated secretory phenotype, linking chromatin-directed repair to aging and disease, and revealing a strategy to uncouple DNA damage from chronic inflammation.

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Designing complex organoids through developmental principles

Brassard and Wells discuss how next-generation human pluripotent stem cell-derived organoids are achieving greater cellular complexity by more faithfully reproducing developmental processes. Advances in tissue interactions, specialized cell incorporation, and bioengineering technologies are enabling increasingly physiologically relevant organoid models to study human development, disease mechanisms, and regenerative biology.

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Generation of human appetite-regulating neurons and tanycytes from pluripotent stem cells

Abay-Nørgaard, Mueller, Hänninen, et al. generate cultures of the hypothalamic arcuate nucleus from hPSCs. They show transcriptional similarity to human ARC and response to appetite-regulating cues. BMP duration regulates ARC versus neighboring VMH fate and reveals the identification of divergent in vitro satiety-promoting POMC neurons of arcuate and non-arcuate origin.

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Evolving strategies for lineage tracing: Genetic markers, synthetic barcodes, and natural variants

This review synthesizes three pillars of lineage tracing—genetic markers, synthetic barcodes, and natural variants—and their integration with single-cell multi-omics and spatial profiling. It discusses computational challenges and offers experimental design guidance to decode cell fate in health and disease.

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Autologous macrophage therapy increases transplant-free survival in cirrhosis: Long-term follow-up of a phase 2 clinical trial

Brennan and Kilpatrick et al. report long-term outcomes in patients with cirrhosis treated with autologous monocyte-derived macrophage therapy. Macrophage-treated patients demonstrated a significantly reduced risk of death or transplant at 4 years. Favorable safety and tolerability support further evaluation of macrophage-based therapy as a potential treatment option.

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Human amygdala-like telencephalic organoids model stress circuitry in assembloid systems

Yang and colleagues generated human amygdala-like telencephalic organoids (hATOs) and amygdala-hypothalamic (hATO-hypoTO) assembloids to model the brain’s stress circuitry. They demonstrate that cortisol triggers stress-related signaling and upregulates the noncoding RNA BCYRN1, which uncovered a molecular mechanism linking stress to synaptic disruption in human neurodevelopment.

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Human retinal organoids functionally bridge a transected optic nerve in a rat model

Gong and colleagues demonstrate that transplanting retinal organoids into a completely transected optic nerve enables partial restoration of visual function by forming a relay-like connection between the eye and brain. This strategy provides a new conceptual framework for repairing severe optic nerve injuries.

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Patient-derived organoids reveal ductal dysfunction and CFTR-modulator responses in chronic pancreatitis

Chronic pancreatitis lacks disease-modifying therapies and robust human models. Engle and colleagues establish patient-derived organoids that preserve epithelial disease programs, reveal heterogeneity, and uncover CFTR dysfunction beyond the inherited variants. Functional rescue with clinically available CFTR modulators provides a precision-medicine framework for interrogating pancreatitis biology and developing targeted interventions for patients.

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Lineage plasticity driven by GATA6 loss fuels colorectal cancer metastasis

Goto and colleagues establish a pro-metastatic colorectal cancer organoid library through the serial orthotopic transplantation of liver metastasis-derived organoids and identify GATA6 loss as a central driver of metastatic epigenetic remodeling. GATA6 loss promotes liver metastasis by inducing multilineage plasticity, including fetal-like reversion and basal-like/squamous reprogramming.

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Quantitative molecular cartography of emergency myelopoiesis reveals conserved modules of hematopoietic activation

Swann et al. conducted a comparative analysis of single-cell RNA-sequencing data from emergency myelopoiesis models, finding that different perturbations act at distinct levels of the hematopoietic hierarchy. They identified a conserved myeloid progenitor-based transcriptional activation module across multiple disease conditions, which informs outcomes in human acute myeloid leukemia.

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