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Stem cells are cells that have the capacity to self-renew by dividing and to develop into more mature, specialised cells. Stem cells can be unipotent, multipotent, pluripotent or totipotent, depending on the number of cell types to which they can give rise.
Lineage transitions are a central feature of prostate development, tumorigenesis and treatment resistance. We discovered that inhibition of mitochondrial pyruvate uptake results in large-scale chromatin remodelling of key lineage-specific genes, antagonizes luminal lineage identity, and alters response to antiandrogen therapy in prostate cancer.
In vivo reprogramming by expression of the transcription factors OCT4, SOX2, KLF4, and MYC (OSKM factors) has been associated with early mortality and cancer. We report that these adverse effects are associated with liver and intestinal dysfunction. Strategic control of OSKM expression in these organs through a newly developed transgenic mouse model reduced adverse effects. Our model yields valuable insights into the potential of in vivo reprogramming for rejuvenation and regeneration.
We discovered expression of SYNGAP1, which encodes the ‘synaptic’ protein SYNGAP1, within human cortical progenitors. In an organoid model of SYNGAP1 haploinsufficiency, cortical neurogenesis and neuronal network activity were disrupted. This finding reveals an unknown function for SYNGAP1 at early stages of development, providing a new framework for understanding the pathophysiology of autism spectrum disorder.
Autosomal Recessive Renal Tubular Dysgenesis (AR-RTD) arises from mutations in Angiotensin II sensing genes, but how they impact the kidney was unclear. This study reveals that delayed angiogenesis at a critical developmental window underlies AR-RTD.
Cultured meat technology promises to alleviate protein shortages, but still faces many challenges. Here, the authors achieve serum-free myogenic differentiation of porcine pre-gastrulation epiblast stem cells and generate meat-like tissue via edible plant-based scaffolds without any animal compounds.
Antigen-restricted mature T cells can be generated from pluripotent stem cells edited to lack endogenous T cell receptors and class I major histocompatibility complexes by introducing the T cell selection components into the stromal microenvironment.
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.
The creation of multiple stem-cell-derived models of mammalian embryogenesis is opening many new doors to study human development and brings a need for scientists to demonstrate responsible dialog over the associated ethical issues.
Recent methodological advances in measurements of geometry and forces in the early embryo and its models are enabling a deeper understanding of the complex interplay of genetics, mechanics and geometry during development.
Research with human embryos and embryo models, this year’s Method of the Year, can be fraught. In contrast, digital embryos could be studied, even perturbed, in computational what-happens-when experiments.
Lineage transitions are a central feature of prostate development, tumorigenesis and treatment resistance. We discovered that inhibition of mitochondrial pyruvate uptake results in large-scale chromatin remodelling of key lineage-specific genes, antagonizes luminal lineage identity, and alters response to antiandrogen therapy in prostate cancer.
