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In this article, Salekdeh and colleagues show that ISL1+ cardiac progenitors can be purified from a heterogeneous population of hESC-derived cardiomyocytes using ALCAM. Transplantation of multipotent ISL1+/ALCAM+ progenitors enhances tissue recovery, restores cardiac function, and improves angiogenesis in a rat model of myocardial infarction, based on cardiac MRI and histology.
Miller et al. describe a strategy to identify candidate master regulators of cell lineage specification. This approach identified BCL11B as a key regulator of human mammary stem cell self-renewal in in vitro progenitor and differentiation assays. Using a combination of 2D and 3D primary cell culture techniques, they show that BCL11B drives stem cell self-renewal by inhibiting basal lineage commitment.
In this article, Mandai and colleagues developed the immune-deficient mouse lines with end-stage retinal degeneration and tested in them the functional maturation of human ESC-derived retinal tissues after transplantation. Light-responsive activities in the host retinal ganglion cells were detected in the transplanted area, which suggests functional potency of these graft tissues.
In this work, Young and colleagues test how stabilization of a large endocytic trafficking complex, the retromer assembly, reduces cellular AD phenotypes in a human neuronal model. Using both patient-derived and genome-edited hiPSCs, they show that enhancement of retromer function affects both APP processing and tau phosphorylation independently.
Sonoda et al. established bone-derived CD271+SSEA-4+ MSCs (DPMSCs) from young and elderly patients and demonstrated that DPMSCs may accelerate cellular senescence through TGF-β2 signaling. TGF-β can change the balance of adipogenesis and osteogenesis of DPMSCs. As a result, it may influence the impaired hematopoiesis observed in elderly patients. Interestingly, the aging phenomena can possibly be reversed by anti-TGF-β antibodies.
In this article, Sun and colleagues show that allogeneic bone marrow and/or umbilical cord-derived mesenchymal stem/stromal cell transplantation both result in good clinical safety and effect in treating drug-refractory systemic lupus erythematosus patients, by introducing a 5- to 8-year follow-up study for all the 81 enrolled patients.
In this article, Bonner-Weir and colleagues show heterogeneous expression of both HNF1β and SOX9 in adult human and murine ductal epithelium. Their expression was dynamic and diminished significantly after replication. Using cell surface markers, they isolated living subpopulations of duct cells with different expression profiles and potential to form organoids.
In this article, Goldhamer and colleagues show that loss of both MyoD and Myf5 in skeletal muscle satellite cells results in regenerative failure following injury. Satellite cell progeny accumulate in injured muscle and continue to express markers of myoblast identity, but do not undergo muscle differentiation, and exhibit a propensity for non-myogenic differentiation.
In this study, Yousefi et al. identify reserve intestinal stem cell-autonomous suppression of mTORC1 activity in response to calorie restriction as the basis for enhanced regeneration of the intestinal epithelium after DNA-damaging injury. Conversely, the authors demonstrate that acute nutrient-based stimulation of mTORC1 prior to injury results in reserve stem cell apoptosis and intestinal regenerative failure.
Rashid and colleagues demonstrate the utility of a high-throughput imaging platform for identification of physiologically relevant extracellular niche factors to advance i-Heps closer to their primary tissue counterparts. The extracellular matrix (ECM) protein screen identified Laminin 411 as an important niche factor facilitating i-Hep-based disease modeling in vitro.
In this article, Pei and colleagues demonstrate the requirement of prostaglandin E2 for the mesoderm specification from hESCs by BMP4 induction. This work reveals a mechanism for the early cell fate determination of hESCs and provides insights into strategies for mesoderm induction or neuroectoderm specification through increasing or blocking the PGE2 signal pathway.
In this article, Marbán and colleagues show that exosomes mediate benefits of cell therapy in mouse and human models of Duchenne muscular dystrophy.
Garcia and colleagues report methods for efficient purification of satellite cells from human skeletal muscle. They use their approaches to demonstrate stem cell functions of endogenous satellite cells and to make human satellite cells accessible for sharing among researchers.
In this article, Ledda and colleagues show that GDNF acting through its receptor GFRα1 plays a critical role in the maturation of cortical progenitors by counteracting FGF2 self-renewal activity on neural stem cells and promoting neuronal differentiation.
In this article, Song and colleagues report a recombinant adeno-associated virus serotype 4-based toolkit comprising several distinct rAAV4 vectors that preferentially target qNSCs within the hippocampus. They demonstrate that rAAV4-mediated transgene expression is robust in qNSCs and allows for lineage tracing, genetic manipulation using the Cre-Lox system, functional analyses using electrophysiology and calcium imaging, and activity manipulation using chemogenetics.
In this article, Khosrotehrani and colleagues isolated a bipotent progenitor from the human placenta that is able to give rise to both endothelial and mesenchymal cells ex vivo. This progenitor was characterized at the cellular and molecular level. They show that these progenitors were in vessel walls and functionally rely on Notch signaling for progenitor function.
Human studies can typically not be used to understand cellular functions of the brain. Astrocytes, important for neuronal circuit regulation and support, lack cellular model characterization and biological translation. Falk, Herland, and colleagues report striking differences in astrocyte models. A pilot screen of Alzheimer's disease-related drugs demonstrates dependence between compound hit finding and astrocytic model biology.
Wang and colleagues show that a chromatin remodeler, BPTF, sustains appropriate functions of hematopoietic stem/progenitor cells (HSPCs). BPTF loss causes bone marrow failure and anemia. The authors further define a BPTF-dependent gene-expression program in HSPCs, which contains key HSC stemness factors. These results demonstrate an essential requirement of the BPTF-associated chromatin remodelers for HSC functionality and adult hematopoiesis.
Here, Finnemann and colleagues demonstrate that F-actin stress fibers in adult stem cell-derived retinal pigment epithelial (RPE) cells predict and cause poor phagocytic activity, a cardinal RPE function. ROCK inhibitor treatment of differentiated RPE monolayers suffices to revert F-actin phenotype and restore phagocytic function. The authors propose F-actin phenotype scoring as a rapid, sensitive, and quantitative assessment of RPE quality.
In this article, Berezikov, van der Meer, and colleagues used stem cell-derived cardiomyocytes to model human cardiac hypertrophy. Their approach provides novel insights into molecular mechanisms behind mechanotransduction and cardiac hypertrophy and lays groundwork for the development of new pharmacological approaches as well as for discovering new potential circulating biomarkers of cardiac dysfunction.