Showing papers in "Cell Stem Cell in 2018"

TL;DR: Important biological and pharmacological disparities in pre-clinical research and human translational studies are highlighted, and analyses of clinical trial failures and recent successes provide a rational pathway to MSC regulatory approval and deployment for disorders with unmet medical needs.

TL;DR: It is possible that ongoing hippocampal neurogenesis sustains human-specific cognitive function throughout life and that declines may be linked to compromised cognitive-emotional resilience.

TL;DR: This work has identified a CAR containing the transmembrane domain of NKG2D, the 2B4 co-stimulatory domain, and the CD3ζ signaling domain to mediate strong antigen-specific NK cell signaling that provides standardized, targeted "off-the-shelf" lymphocytes for anti-cancer immunotherapy.

TL;DR: It is argued that there is currently no reason to abandon the idea that adult-generated neurons make important functional contributions to neural plasticity and cognition across the human lifespan.

TL;DR: It is shown that activation of Wingless/Integrated and EGF and inhibition of TGF-β, histone deacetylase, and Rho-associated protein kinase enable long-term culture of human villous cytotrophoblast (CT) cells, which will provide a powerful tool to study human trophoblast development and function.

TL;DR: The design considerations for single and multi-organ Oocs are reviewed, remaining challenges are discussed, and the potential impact of OOCs as a fast-track opportunity for tissue engineering to advance drug development and precision medicine is highlighted.

TL;DR: Functional heterogeneity of Wnt niche independency in PDAC that is non-genetically formed through tumor progression is revealed, and CRISPR-Cas9-based genome editing of PDAC driver genes demonstratedNon-genetic acquisition of WNT niche independence during pancreas tumorigenesis.

TL;DR: A primary gastric cancer organoid biobank that comprises normal, dysplastic, cancer, and lymph node metastases from 34 patients, including detailed whole-exome and transcriptome analysis, provides a useful resource for studying both cancer cell biology and precision cancer therapy.

TL;DR: Brain-derived neurotrophic factor and its cognate receptor NTRK2 were expressed in the neuronal lineage during organoid differentiation, andhibiting this pathway improved organoid formation by reducing neurons by 90% without affecting kidney differentiation, highlighting the power of single-cell technologies to characterize and improve organoids differentiation.

TL;DR: It is demonstrated that the epithelium is transiently reprogrammed into a primitive state in a mouse dextran sulfate sodium (DSS) colitis model, and this provides a simple model for tissue regeneration, implicating cellular reprogramming as an essential element.

TL;DR: The clinical manifestations of CH, mechanisms contributing to its development, the role of CH in clonal evolution toward leukemia, and the contribution of CH to non-hematological disease states are discussed.

TL;DR: A fully automated, HTS-compatible platform for enhanced differentiation and phenotyping of human kidney organoids that reveals an unexpected role for myosin in polycystic kidney disease and establishes an attractive platform for multidimensional phenotypic screening.

TL;DR: Recent bioengineering advances in creating functional blood macro and microvessels, particularly featuring stem cells as a seed source are explored, highlighting progress in integrating engineered vascular tissues with the host after implantation as well as the exciting pre-clinical and clinical applications.

TL;DR: A refined organoid culture condition for intestinal epithelia is established that allows human intestinal organoids to concurrently undergo multi-differentiation and self-renewal and offers a viable strategy for modeling human intestinal tissues and diseases in an in vivo relevant context.

TL;DR: This Review discusses transcriptome-based lineage trajectory prediction algorithms, single-cell genetic lineage tracing, and the promising combination of these techniques for stem cell and cancer research.

TL;DR: This work allows for the reconstruction of transcriptional programs inherent to sequential cell fate transition during human spermatogenesis and has implications for deciphering male-related reproductive disorders.

TL;DR: It is found that mutations in PPM1D (protein phosphatase Mn2+/Mg2+-dependent 1D), a DNA damage response regulator that is frequently mutated in CH, were present in one-fifth of patients with therapy-related acute myeloid leukemia or myelodysplastic syndrome and strongly correlated with cisplatin exposure.

TL;DR: In this article, the authors review the current knowledge on HSC-dependent cell lineages and HSCindependent tissue-resident hematopoietic cells and how they arise during embryonic development.

TL;DR: It is shown that a 24 hr fast augments intestinal stem cell (ISC) function in young and aged mice by inducing a fatty acid oxidation (FAO) program and that pharmacological activation of this program mimics many effects of fasting.

TL;DR: Preserving endosteal endothelium with the small molecule deferoxamine or a genetic approach rescues HSCs loss, promotes chemotherapeutic efficacy, and enhances survival, suggesting that preventing degradation of the endostealing vasculature may improve current paradigms for treating AML.

TL;DR: The results support the safety of NSI-566 transplantation into the SCI site and early signs of potential efficacy in three of the subjects warrant further exploration of NS i566 cells in dose escalation studies, and encouraging secondary data are reported.

TL;DR: A rapid increase in the frequency and absolute number of Tet2-KO mature myeloid cells and HSPCs in response to inflammatory stress is shown, which results in enhanced production of inflammatory cytokines, including interleukin-6 (IL-6), and resistance to apoptosis.

TL;DR: It is hypothesized that MuSCs recruit capillary ECs via VEGFA, and in return, ECs maintain MuSC quiescence though Dll4, and it is shown that this proximity to the blood vessels was associated with MuSC self-renewal.

TL;DR: An unexpected link between membrane phospholipid remodeling and cholesterol biosynthesis is revealed and it is demonstrated that cholesterol itself acts as a mitogen for ISCs and drives ISC proliferation and tumorigenesis.

TL;DR: A role for human T lymphocytes as cell death inducers of induced pluripotent stem cell (iPSC)-derived MBNs in sporadic PD is shown and indicates a critical role for IL-17-producing T lymphocyte in sporadicPD.

TL;DR: It is found that hypertrophic signaling is not effectively activated during monolayer-based cardiac differentiation, thereby preventing expression of HOPX and its activation of downstream genes that govern late stages of cardiomyocyte maturation.

TL;DR: The most recent findings regarding the causes and consequences of HSC heterogeneity are reviewed, their far-reaching implications are discussed, and it is suggested that so-called continuum-based models may help consolidate apparently divergent experimental observations in this field.

TL;DR: Recent advances in SCNT technology and its potential applications for both reproductive and therapeutic cloning are summarized.

TL;DR: Current efforts aimed at generating a sustainable source of functional human stem cell-derived insulin-producing islet cells for cell transplantation are described and state-of-the-art efforts to protect such cells via immune modulation and encapsulation strategies are presented.

TL;DR: It is shown that transplanted somatic and directly induced NSCs are able to ameliorate chronic CNS inflammation by reducing succinate levels in the cerebrospinal fluid, thereby decreasing mononuclear phagocyte infiltration and secondary CNS damage.