Dr. Deepak Srivastava is the President of the Gladstone Institutes and Director of the Roddenberry Stem Cell Center. His lab is focused on the gene networks that guide cardiac development. He talks about their recent work investigating heart defects in Down syndrome and strategies for delivering therapies to the heart. He also talks about how to incentivize the development and commercialization of cell and gene therapies. (41:50)

Heart and Ganglion Development – Researchers fused human sympathetic ganglion organoids and heart-forming organoids to construct functional connections between the sympathetic ganglia and the heart. (2:38)

Periportal Liver Assembloids – Patient-specific periportal liver assembloids retain the histological arrangement, gene expression, and cell interactions of periportal liver tissue. (9:40)

PIEZO1 and Drug-Induced Cardiotoxicity – Restoring endothelial PIEZO1 protects against tyrosine kinase inhibitor-induced hypertension and cardiac dysfunction. (19:28)

Somite and Neural Tube Co-Development – Scientists developed human trunk-like structures that have morphologically organized somites and a neural tube that form through self-organized, endogenous signaling. (28:43)

Image courtesy of Dr. Deepak Srivastava

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Dr. Hans Clevers is a Professor of Molecular Genetics and Distinguished Group Leader at the University of Utrecht. In this episode, he discusses snake gut and lung organoids, transitioning from academia to industry, and the challenges and complexities of creating a cell therapy. (44:26)

Computers Made From Human Brain Cells – Researchers have shown that structured neuronal firing sequences appear in spontaneous activity of human and murine brain organoids. (2:37)

Organoids Replicate Vascular Pathology – Scientists have developed a blood vessel organoid model from Hutchinson-Gilford progeria syndrome-mutant hESCs. (12:01)

Effects of Spaceflight on Stem Cells – Analyses of nine astronauts before, during, and after three short-duration International Space Station missions shows space-associated stem cell hallmarks of aging and resilience. (21:14)

The Role of Lysosomes in HSC Aging – Reversing lysosomal dysfunction restores youthful state in aged hematopoietic stem cells. (33:25)

Photo Reference: Courtesy of Hans Clevers

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Dr. Thomas Vierbuchen is Assistant Professor of Developmental Biology at Memorial Sloan Kettering Cancer Center. In this episode, he talks about using PSCs to model neurodevelopmental processes. He also discusses his direct reprogramming work and his lab’s recent study on OTX2 in gastrulation. (42:02)

Restoring Function After Spinal Cord Injury: In a non-human primate model of spinal injury, researchers grafted ESC-derived spinal cord neural stem cells and improved forelimb function. (2:00)

Improving HSC Expansion: Inhibiting ferroptosis augments the expansion of HSCs ex vivo. (11:40)

Cardiomyocytes and Macrophage Reprogramming: Injury-induced Clusterin+ cardiomyocytes promote neonatal heart regeneration by reprogramming macrophages. (21:27)

Bone Marrow Organoids: A 3D in vitro bone marrow model captures phenotypic, structural, and functional features of human endosteal bone marrow niches. (33:03)

Image courtesy of Dr. Thomas Vierbuchen

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Dr. Sumru Bayin is a Group Leader at the Gurdon Institute at the University of Cambridge. She talks about her work on regeneration in the neonatal mouse cerebellum and how cerebellar interneurons differentiate. She also discusses organizing a workshop to facilitate collaborations in regenerative biology, and her memories of the late Sir John Gurdon. (40:30)

Heart-Macrophage Assembloids – Human heart–macrophage assembloids enable the study of immune–cardiac interactions and the modeling of arrhythmias. (1:41)

Human Nucleus Basalis Organoids – Human nucleus basalis of Meynert organoids can fuse with human cortical organoids and are used to model neurodevelopmental disorders. (11:15)

A Brain Organoid Atlas – Scientists used iPSCs from patients with neurodevelopmental disorders to generate a brain organoid atlas. (20:19)

Human Cortex Development – Lineage tracing in human tissue samples provides insight into lineage relationships between cortical cell types. (28:03)

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Dr. Juan Melero-Martin is an Associate Professor and the Endowed Chair in Cardiac Surgery at Boston Children’s Hospital. His lab uses bioengineering principles to understand how vascular networks are formed and the mechanisms by which the vasculature modulates the engraftment and activity of various human stem cells. (42:03)

Chromosomal Genes Linked to Heart Disease – Scientists identified HMGN1, a nuclear binding protein, as a key contributor to trisomy 21-related congenital heart defects. (1:46)

Questioning Common Technique for Assessing IVF Embryos  – Live imaging of late-stage preimplantation human embryos suggests that abnormalities can arise at a later stage of development than previously thought. (14:14)

Vitamin C Protects Ovaries – Scientists have shown that oral vitamin C protects against ovarian aging in primates. (24:07)

Multi-Branching Cell Differentiation Trajectories – A new Hodge Laplacian model has advanced single-cell multimodal data analysis by providing highly reliable results for complex multi-branching trajectories. (33:58)

Photo Reference: Courtesy of Dr. Juan Melero-Martin.

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Dr. Carole LaBonne is the Erastus Otis Haven Professor of Molecular Biosciences at Northwestern University. Her lab studies the genesis of neural crest stem cells at the level of the signaling pathways and transcription factors that comprise the neural crest gene regulatory network. They also study how these mechanisms contribute to exit from pluripotency and the subsequent lineage restriction of neural crest cells to their derivative cell types that collectively define vertebrates. (39:45)

Creating Modified Cows and Sheep from Haploid Stem Cells – Scientists have successfully derived haploid androgenetic ESCs from cattle and sheep, and have developed a novel method to generate offspring from these cells. (4:33)

Embryonic Stem Cells from Birds – Researchers have succeeded in deriving and maintaining authentic ESCs from chickens and seven other bird species. (13:48)

Mutation Hotspots Reveal Spermatogonia Clonal Growth – As men age, harmful genetic mutations in sperm not only accumulate but are also favored during sperm production, giving them a reproductive advantage. (20:35)

Canine iPSC Technology – Researchers have established culture conditions for canine iPSCs. (31:10)

Photo Reference: Courtesy of Dr. Carole LaBonne

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Dr. Paul Tesar is the Director of the Institute for Glial Sciences and the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics at Case Western Reserve University. His lab uses PSCs to model neurological development and disease with a specific focus on oligodendrocytes and astrocytes. He talks about his work on oligodendrocyte maturation, advancing research into the commercial and clinical sectors, and mentoring the next generation of scientists. (42:17)

Spatially Patterned Kidney Assembloids – Genome-edited kidney progenitor assembloids recapitulate hallmarks of human autosomal dominant polycystic kidney disease. (5:50)

Transposable Elements Controlling Cell Fate – This study highlights the role of transposable elements as mechano-response enhancer elements that control human cell fate and gene expression. (13:54)

Cardiac Injury Recovery – Targeting a remote injury response in a non-cardiomyocyte cell type rapidly promotes post-myocardial infarction recovery of non-regenerative hearts. (22:47)

Intestinal Fibrosis in Crohn’s Disease – A mouse model of creeping fat recapitulates key features of Crohn’s disease strictures. (31:40)

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Dr. Lars Velten is a Group Leader at the Centre for Genomic Regulation in Barcelona. He talks about his research on cell-state-specific enhancers in hematopoiesis and lineage tracing techniques to study blood aging. He also discusses combining generative AI with wet lab techniques and the advantages of risk-taking in basic research. (40:41)

HSPC Aging in Space – Spaceflight reduces telomere maintenance and HSPC self-renewal. (1:50)

Modeling Myelin Repair – Brain organoids with integrated microglia enabled the investigation of demyelination and remyelination. (14:45)

Gastric Cancer Organoids – CRISPR screens with human tumor organoids revealed metabolic dependencies and synthetic lethal pairs. (25:55)

Gastroids to Model Stomach Development – This study reveals a principle for instructing gastric patterning and provides a platform for advancing knowledge of stomach organogenesis. (33:10)

Image courtesy of Dr. Lars Velten

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Dr. Alice Soragni is an Associate Professor at the University of California, Los Angeles. She talks about her work on patient-derived organoids and how they can be adapted for drug screening. She also discusses how she transitioned from structural biology to research on protein aggregation and rare diseases, and the current social media landscape for scientists. (45:20)

Optogenetic Control of Morphogen Production – Researchers established a model that recapitulates Sonic hedgehog-mediated patterning of the vertebrate neural tube. (4:17)

Oligodendrocyte Maturation – Reducing SOX6 levels unlocks oligodendrocyte maturation and myelination. (15:45)

CAR T Therapy for Kidney Disease – Targeting extracellular matrix-producing cells with CAR T therapy is a therapeutic strategy for chronic kidney disease. (24:44)

Lung Xenotransplantation – A lung from a gene-edited pig was transplanted into a brain-dead human recipient. (35:00)

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Dr. Zhongwei Li is an Associate Professor at the University of Southern California. His lab focuses on kidney organogenesis with translational applications of kidney regeneration and disease modeling. He talks about his work on PSC-derived nephron progenitors and drug discovery applications for polycystic kidney disease. (40:12)

Chemically Induced Embryo Founder Cells: A small-molecule-only approach was used to induce mouse embryonic stem cells into embryo founder cells, which generated a mouse embryo model. (1:45)

Transgene-Free Embryo Models: Scientists generated transgene-free stem cell-based embryo models solely from mouse naïve PSCs. (13:25)

Hypoimmune CAR T Cells: Allogeneic hypoimmune CAR T cells do not induce an immune response in patients. (21:15)

Reconstructing PSC-Islets: PSC-islets comprising all five endocrine subtypes were reconstructed and transplanted into mice. (32:03)

Image courtesy of Dr. Zhongwei Li

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