Cell Stem Cell

4 Sept 2025

Our latest issue is out! Highlights include reports on the immune response to allogeneic cell therapies in clinical trials with iPS-DA neurons and primary hypoimmune CAR-T cells, a PDAC organoid biobank that IDed use of statins in a clinical trial, & more! www.cell.com/cell-stem-ce...

dlvr.itProgrammable apoptosis circuits enable subtractive engineering of stem cell-derived organoids and embryoidsThe authors introduce a programmable synthetic biology framework for tissue construction from hiPSCs through subtractive multicellular engineering. By selectively removing undesired cells during development via synthetic apoptosis circuits, this approach enhances tissue maturation and refines morphogenesis across organoid and embryoid models.

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Online Now! Programmable apoptosis circuits enable subtractive engineering of stem cell-derived organoids and embryoids #stemcells

dlvr.itA self-organized tri-lineage bone model in liquefied microcapsules captures matrix dynamics in early remodelingMano and colleagues have developed a self-organized bone-like model by co-encapsulating stromal and monocytic cells in liquefied gelatin microcapsules. Their direct interaction effectively supports the emergence of osteoblast-, osteocyte-, and osteoclast-like phenotypes, facilitating cellular crosstalk and promoting mineralized matrix formation and turnover without the need for lineage-specific induction.

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Online Now! A self-organized tri-lineage bone model in liquefied microcapsules captures matrix dynamics in early remodeling #stemcells

dlvr.itPhase separation of Rbpms sequesters translation elongation machinery to preserve hematopoietic stem cell functionYu and colleagues reveal that hematopoietic stem cells employ Rbpms condensates to spatially restrict the translation elongation machinery. By slowing protein synthesis and ensuring proper protein folding, this mechanism preserves proteostasis, quiescence, and LT stem cell function.

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Online Now! Phase separation of Rbpms sequesters translation elongation machinery to preserve hematopoietic stem cell function #stemcells

dlvr.itOrganotypic vascularization improves maturation of human stem cell-derived islets and restores normoglycemia in diabetic miceWang et al. generate vascularized pancreatic islet organoids (VPIOs) containing organotypic vascular networks exhibiting endothelial fenestration. Vascularization enhances β cell maturation in vitro and survival under hypoxia. Following transplantation into diabetic mice, VPIOs establish functional connections with the host vasculature and effectively restore normoglycemia.

Online Now! Organotypic vascularization improves maturation of human stem cell-derived islets and restores normoglycemia in diabetic mice #stemcells

dlvr.itGenome-wide CRISPR screen reveals that Wnt signaling regulates lipid accumulation in APOE4 oligodendrocytesAkay et al. use a genome-wide CRISPR screen to identify Wnt signaling as a regulator of lipid accumulation in APOE4 oligodendrocytes. Stimulating Wnt signaling by inhibiting GSK3B reduced lipid droplets and improved myelination in iPSC-derived brain organoids and APOE4;PS19 mice.

Online Now! Genome-wide CRISPR screen reveals that Wnt signaling regulates lipid accumulation in APOE4 oligodendrocytes #stemcells

dlvr.itSkin fibroblast lineage tracing reveals layer-specific cooperation in wound repairGuo et al. develop a multiplex lineage-tracing platform to systematically profile fibroblasts across all five anatomical layers of the skin. They uncover a highly coordinated, multi-stage sequence of fibroblast mobilization and architectural reorganization during wound healing, demonstrating that cell-intrinsic programs predominate over local microenvironments to govern layer-specific contributions.

Online Now! Skin fibroblast lineage tracing reveals layer-specific cooperation in wound repair #stemcells

dlvr.itRapid CAR-T manufacturing with low-intensity priming enhances CAR-T cell fitness and limits inflammatory programming in a phase 1 studyYang and colleagues show that low-intensity priming during rapid chimeric antigen receptor (CAR)-T manufacturing preserves T cell fitness while restraining inflammatory programming. PrimeCAR cells maintain stemness-associated and proliferative responses with reduced myeloid-activating inflammation, and early-phase studies in B cell malignancies demonstrate encouraging clinical activity with few severe cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) events.

Online Now! Rapid CAR-T manufacturing with low-intensity priming enhances CAR-T cell fitness and limits inflammatory programming in a phase 1 study #stemcells

dlvr.itSingle-cell CRISPR screen maps epigenetic regulators of lineage specification and malignancies in human HSPCsYuan et al. establish a scalable single-cell CRISPR platform in primary human HSPCs, linking 322 regulator perturbations to cell states and gene programs. The atlas identifies regulators associated with long-term repopulation and lineage-biased outputs and nominates PRDM10 as a candidate AML dependency.

Online Now! Single-cell CRISPR screen maps epigenetic regulators of lineage specification and malignancies in human HSPCs #stemcells

dlvr.itTransplantation of Expanded Fetal Intestinal Progenitors Contributes to Colon Regeneration after Injury(Cell Stem Cell 13, 734–744; December 5, 2013)

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Online Now! Transplantation of Expanded Fetal Intestinal Progenitors Contributes to Colon Regeneration after Injury #stemcells

dlvr.itMouse Cutaneous Melanoma Induced by Mutant BRaf Arises from Expansion and Dedifferentiation of Mature Pigmented Melanocytes(Cell Stem Cell 21, 679–693.e1–e6; November 2, 2017)

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Online Now! Mouse Cutaneous Melanoma Induced by Mutant BRaf Arises from Expansion and Dedifferentiation of Mature Pigmented Melanocytes #stemcells

Have new research in organoids, NAMs or human tissue models? Submit an abstract to #CPSOrganoidsNAMs27 for a chance to present your work in Bruges, Belgium, April 28–30, 2027 📅 Deadline: January 22, 2027 🔗 http://dlvr.it/TVpGZr @CellPressEvents

dlvr.itImmunoids: Building immunocompetent organoids from human pluripotent stem cellsO’Hern et al. review advances in modeling immunity and tissue function using self-organizing hPSC-derived immunocompetent organoids, termed “immunoids.” They outline priorities for advancing the field, including standardization and biologically informed design principles to improve the physiological fidelity and translational value of next-generation models.

Immunoids: Building immunocompetent organoids from human pluripotent stem cells

dlvr.itSystemic delivery of phagocytosis-shielded retroviral vectors enables in vivo HSC gene therapy for sickle cell diseaseKlatt et al. show that phagocytosis-shielded, BaEVRLess-pseudotyped retroviral vectors transduce human hematopoietic stem cells directly in vivo in mobilized humanized mice. Chemoselection enriches gene-marked cells, and erythroid-specific knockdown of BCL11A and ZNF410 derepresses fetal globin to therapeutically relevant levels for sickle cell disease.

Systemic delivery of phagocytosis-shielded retroviral vectors enables in vivo HSC gene therapy for sickle cell disease

dlvr.itGenomic and transcriptomic quality control for an autologous iPSC-derived cell therapy for Parkinson’s diseaseBratt-Leal et al. report the preclinical data supporting initiation of a clinical trial investigating autologous dopaminergic neuron precursor cell therapy for moderate to advanced Parkinson’s disease patients. Whole-genome sequencing and RNA-seq analysis underpin a quality control program to ensure safety and efficacy.

Genomic and transcriptomic quality control for an autologous iPSC-derived cell therapy for Parkinson’s disease

dlvr.itH3K27M drives OPC stemness and intrathecal therapeutic vulnerability in brainstem glioma organoidsZhang and colleagues established a patient-derived brainstem glioma organoid (BSGO) platform that preserved tumor microenvironment and enabled mechanistic and therapeutic discovery. They uncovered mechanism of H3K27M-driven tumor stemness in diffuse midline glioma and translated organoid-guided screening into personalized treatment, demonstrating the potential of intrathecal differentiation therapy.

H3K27M drives OPC stemness and intrathecal therapeutic vulnerability in brainstem glioma organoids

dlvr.itClinical base editing for β-hemoglobinopathies across different genetic backgroundsLiu et al. demonstrate the clinical efficacy of the transformer base editor in one patient with SCD and three non-Chinese patients with TDT, achieving durable pan-cellular HbF induction, sustained elimination of VOCs, and persistent transfusion independence during follow-up.

Clinical base editing for β-hemoglobinopathies across different genetic backgrounds

dlvr.itIGF2 acts downstream of Hippo signaling to regulate organ growth and restore liver regeneration in agingZhong and colleagues reveal a mechanism behind organ size control in development and regeneration. High IGF2 levels drive and coordinate rapid fetal and neonatal growth, while IGF2 silencing—upon postnatal Hippo signaling activation—limits growth and determines organ size. Restoring IGF2 expression enhances tissue repair and reverses age-related regenerative defects.

IGF2 acts downstream of Hippo signaling to regulate organ growth and restore liver regeneration in aging

dlvr.itEndothelialized callus organoids drive rapid regeneration of critical-size segmental long bone defectsEndothelial cells instruct the early developmental program of human periosteum-derived callus organoids. Scalable organoid aggregates guide host-mediated regeneration through endochondral ossification, restoring critical-size skeletal defects.

Endothelialized callus organoids drive rapid regeneration of critical-size segmental long bone defects

dlvr.itEpi-Allele elicits compensatory expression of the non-targeted allele and prevents haploinsufficiency in dominant genetic diseasesZhou and colleagues present Epi-Allele, an allele-specific epigenetic silencing strategy that rebalances allelic expression while preserving total gene output. In HCM models, Epi-Allele silences pathogenic alleles, induces compensatory upregulation of non-targeted alleles, and alleviates disease without causing therapeutic haploinsufficiency.

Epi-Allele elicits compensatory expression of the non-targeted allele and prevents haploinsufficiency in dominant genetic diseases

dlvr.itEngineered human iPSC-derived dendritic cells dressed with tumor MHC complexes as a cancer vaccineBlelloch and colleagues create genetically engineered universal human iPSCs, differentiate them into CCR7+ migratory dendritic cells, and dress them with tumor-derived MHC class I-antigen complexes to develop a personalized cancer vaccine. They validate the approach using cancer cell lines and matching patient tumor/blood samples, both in vitro and in vivo.

Engineered human iPSC-derived dendritic cells dressed with tumor MHC complexes as a cancer vaccine

dlvr.itThe accessory makes the drug: ASO-delivered siRNA enters the human CNS for ALSIn a recent article in Nature Medicine, Chen et al. describe a first-in-human study using an ASO tag to deliver a SOD1 siRNA to the central nervous system (CNS), potentially achieving faster, more extensive, and better-tolerated SOD1-lowering in ALS patients.1

The accessory makes the drug: ASO-delivered siRNA enters the human CNS for ALS

dlvr.itEditing cells in place: Targeted in vivo gene editing of hematopoietic stem cellsTraditional ex vivo hematopoietic stem cell (HSC) gene therapy faces manufacturing challenges. A recent study in Nature Biomedical Engineering demonstrates that antibody-engineered lipid nanoparticles achieve efficient and durable in vivo editing of HSCs in humanized mice, offering a promising therapeutic strategy for genetic blood diseases.

Editing cells in place: Targeted in vivo gene editing of hematopoietic stem cells

dlvr.itFlipping the fetal switch across β-hemoglobinopathiesLiu et al. extend the application of transformer base editing of HBG1/2 promoters from transfusion-dependent β-thalassemia alone to one patient with sickle cell disease and three patients with geographically diverse β-thalassemia genotypes. The responses are meaningful, but scale, genomic surveillance, burden of cure, and access now define the translational test.

Flipping the fetal switch across β-hemoglobinopathies

dlvr.itActivins and BMPs: The yin and yang of diffuse midline gliomasPatient-derived models of diffuse midline gliomas (DMGs) remain challenging for interrogating tumor biology and investigating novel therapeutics. Xie et al. develop a robust patient-derived brainstem glioma organoid (BSGO) platform, reveal an Activin B-ACVR2A signaling pathway that promotes DMG growth, and identify a promising triple intrathecal therapy to inhibit it.

Activins and BMPs: The yin and yang of diffuse midline gliomas

dlvr.itRight size, right time: The Hippo-IGF2 axis calibrates liver growth and regenerationThe imprinted gene IGF2 is a well-characterized growth factor regulating organ proliferation during embryogenesis, while Hippo signaling has been demonstrated as an important regulator of organ size. This study by Zhong et al. mechanistically connects Hippo-controlled Igf2 expression in postnatal liver growth and regeneration.

Right size, right time: The Hippo-IGF2 axis calibrates liver growth and regeneration

dlvr.itSilencing the mutant allele without compromising gene dosageAllele-selective silencing offers a strategy to suppress pathogenic alleles in dominant genetic disorders but may alter total gene dosage when the remaining allele does not compensate. Wang et al. show that SNP-guided epigenetic repression of mutant alleles can elicit compensatory expression from non-targeted alleles, highlighting considerations for future therapeutic applications.

Silencing the mutant allele without compromising gene dosage

dlvr.itVitamin C attenuates primate bone marrow aging at the molecular and progenitor level(Cell Stem Cell 33, 1379–1397.e1–e8; August 6, 2026)

Online Now! Vitamin C attenuates primate bone marrow aging at the molecular and progenitor level #stemcells

dlvr.itSystemic delivery of phagocytosis-shielded retroviral vectors enables in vivo HSC gene therapy for sickle cell diseaseKlatt et al. show that phagocytosis-shielded, BaEVRLess-pseudotyped retroviral vectors transduce human hematopoietic stem cells directly in vivo in mobilized humanized mice. Chemoselection enriches gene-marked cells, and erythroid-specific knockdown of BCL11A and ZNF410 derepresses fetal globin to therapeutically relevant levels for sickle cell disease.

4w

Online Now! Systemic delivery of phagocytosis-shielded retroviral vectors enables in vivo HSC gene therapy for sickle cell disease #stemcells

dlvr.itImmunoids: Building immunocompetent organoids from human pluripotent stem cellsO’Hern et al. review advances in modeling immunity and tissue function using self-organizing hPSC-derived immunocompetent organoids, termed “immunoids.” They outline priorities for advancing the field, including standardization and biologically informed design principles to improve the physiological fidelity and translational value of next-generation models.

4w

Online Now! Immunoids: Building immunocompetent organoids from human pluripotent stem cells #stemcells

dlvr.itGenomic and transcriptomic quality control for an autologous iPSC-derived cell therapy for Parkinson’s diseaseBratt-Leal et al. report the preclinical data supporting initiation of a clinical trial investigating autologous dopaminergic neuron precursor cell therapy for moderate to advanced Parkinson’s disease patients. Whole-genome sequencing and RNA-seq analysis underpin a quality control program to ensure safety and efficacy.

17 Sept

Online Now! Genomic and transcriptomic quality control for an autologous iPSC-derived cell therapy for Parkinson’s disease #stemcells

dlvr.itH3K27M drives OPC stemness and intrathecal therapeutic vulnerability in brainstem glioma organoidsZhang and colleagues established a patient-derived brainstem glioma organoid (BSGO) platform that preserved tumor microenvironment and enabled mechanistic and therapeutic discovery. They uncovered mechanism of H3K27M-driven tumor stemness in diffuse midline glioma and translated organoid-guided screening into personalized treatment, demonstrating the potential of intrathecal differentiation therapy.

16 Sept

Online Now! H3K27M drives OPC stemness and intrathecal therapeutic vulnerability in brainstem glioma organoids #stemcells

dlvr.itClinical base editing for β-hemoglobinopathies across different genetic backgroundsLiu et al. demonstrate the clinical efficacy of the transformer base editor in one patient with SCD and three non-Chinese patients with TDT, achieving durable pan-cellular HbF induction, sustained elimination of VOCs, and persistent transfusion independence during follow-up.

9 Sept

Online Now! Clinical base editing for β-hemoglobinopathies across different genetic backgrounds #stemcells

dlvr.itIGF2 acts downstream of Hippo signaling to regulate organ growth and restore liver regeneration in agingZhong and colleagues reveal a mechanism behind organ size control in development and regeneration. High IGF2 levels drive and coordinate rapid fetal and neonatal growth, while IGF2 silencing—upon postnatal Hippo signaling activation—limits growth and determines organ size. Restoring IGF2 expression enhances tissue repair and reverses age-related regenerative defects.

Online Now! IGF2 acts downstream of Hippo signaling to regulate organ growth and restore liver regeneration in aging #stemcells

dlvr.itEndothelialized callus organoids drive rapid regeneration of critical-size segmental long bone defectsEndothelial cells instruct the early developmental program of human periosteum-derived callus organoids. Scalable organoid aggregates guide host-mediated regeneration through endochondral ossification, restoring critical-size skeletal defects.

Online Now! Endothelialized callus organoids drive rapid regeneration of critical-size segmental long bone defects #stemcells

Present your research in Bruges! We're now accepting abstracts for #CPSOrganoidsNAMs27 from scientists advancing organoids, NAMs, disease modeling, drug discovery, and more. 🗓️ Abstracts due: January 22, 2027 🔗 http://dlvr.it/TVNXWS @CellPressEvents