Nicotinamide Ameliorates Disease Phenotypes in a Human iPSC Model of Age-Related Macular Degeneration
Bhaskar Chanda Stem Cell Saini et al. show that hiPSC-derived RPE, including ARMS2/HTRA1 homozygotes, from AMD patients exhibit higher complement and inflammatory factors compared to healthy controls. Nicotinamide treatment reduces these and other AMD-related molecules with no observed cytotoxicity. Pursuing nicotinamide’s mechanism of action should reveal new therapeutic approaches for AMD.
Human iPSC-Derived Neural Progenitors Are an Effective Drug Discovery Model for Neurological mtDNA Disorders
Bhaskar Chanda Stem Cell Prigione and colleagues show that neural progenitors differentiated from patient-derived iPSCs are an effective modeling tool for neuronal disease associated with mtDNA mutations and can be used for drug screening.
Recent Zika Virus Isolates Induce Premature Differentiation of Neural Progenitors in Human Brain Organoids
Bhaskar Chanda Stem Cell Gabriel and colleagues show that two recently isolated Zika strains efficiently infect neural progenitors in human brain organoids and cause premature differentiation in a way that closely resembles Zika-associated microcephaly and differs from the effects seen with an older and extensively passaged strain.
Human iPSC-Derived Cerebral Organoids Model Cellular Features of Lissencephaly and Reveal Prolonged Mitosis of Outer Radial Glia
Bhaskar Chanda Stem Cell Bershteyn and colleagues show that cerebral organoid modeling of lissencephaly using iPSCs derived from Miller-Dieker syndrome patients can characterize cellular and neurodevelopmental disease phenotypes and identify a mitotic defect in outer radial glia, a cell type that is particularly important for human cortical development.
Bhaskar Chanda Stem Cell Guimarães-Camboa et al. permanently labeled pericytes and vascular smooth muscle of multiple organs in vivo and followed the fate of these cells in aging and injury models. Their analyses showed that, in vivo, pericytes did not behave as stem cells, challenging the current view of pericytes as tissue-resident multipotent progenitors.
RNA Helicase DDX5 Inhibits Reprogramming to Pluripotency by miRNA-Based Repression of RYBP and its PRC1-Dependent and -Independent Functions
Bhaskar Chanda Stem Cell RNA-binding proteins have poorly defined roles in somatic cell reprogramming. Li et al. show that the RNA-binding protein DDX5 erects an epigenetic barrier to reprogramming. DDX5 controls RYBP through microRNA-125b to suppress specific somatic genes through deposition of H2AK119ub1 while activating an OCT4-KDM2B pluripotent gene program.
Glioblastoma Cancer Stem Cells Evade Innate Immune Suppression of Self-Renewal through Reduced TLR4 Expression
Bhaskar Chanda Stem Cell Alvarado et al. demonstrate that glioblastoma cancer stem cells express a lower level of the innate immune receptor TLR4 than surrounding cells, which allows them to avoid inhibitory innate immune signaling that would otherwise suppress self-renewal.
Immunosuppression via Loss of IL2rγ Enhances Long-Term Functional Integration of hESC-Derived Photoreceptors in the Mouse Retina
Bhaskar Chanda Stem Cell Lamba and colleagues show that immunosuppression can significantly improve the survival and functional integration of hESC-derived cells into recipient mouse retinas as far out as 9 months, suggesting that immunosuppression may be a useful way to enhance clinical cell transplantation outcomes for patients even in a location traditionally considered immune-privileged.
Human AML-iPSCs Reacquire Leukemic Properties after Differentiation and Model Clonal Variation of Disease
Bhaskar Chanda Stem Cell Chao et al. show that MLL-rearranged AML patient cells can be reprogrammed into induced pluripotent stem cells (iPSCs). These cells reacquire leukemic properties and associated methylation/gene expression patterns after hematopoietic differentiation and provide a means to study the differential properties of specific disease subclones.