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Updated: 12 hours 45 min ago

Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson's Disease

Thu, 09/21/2017 - 00:00
In this study, Lee and colleagues show that simple VC treatment during donor NSC preparation enhances cell therapeutic outcomes in a PD animal model, along with enriched midbrain DA neuron engraftment. The VC effect was achieved by a long-lasting epigenetic activation of midbrain DA neuron-specific developmental and phenotype gene expressions via DNA and repressive histone code demethylation.

IAP-Based Cell Sorting Results in Homogeneous Transplantable Dopaminergic Precursor Cells Derived from Human Pluripotent Stem Cells

Thu, 09/21/2017 - 00:00
In this article, Knöbel and colleagues identified IAP as a cell surface marker for mesDA progenitor cells. Immunomagnetic sorting for IAP+ led to reproducible and homogeneous cell compositions. Intrastriatal transplantation of sorted cells at day 16 of differentiation in a PD rat model resulted in functional recovery, and grafts were more homogeneous in size and DA neuron density than unsorted cells.

Keratin-14-Positive Precursor Cells Spawn a Population of Migratory Corneal Epithelia that Maintain Tissue Mass throughout Life

Thu, 09/21/2017 - 00:00
Richardson et al. demonstrate the biphasic nature of corneal epithelial development during late embryogenesis. Progenitor cells of the central cornea are lost during post-natal life, replaced by those in the peripheral limbus, whose age-related dynamics align with population asymmetry. Apoptosis within the central corneal epithelium alters normal clonal migration patterns.

SOX7 Is Required for Muscle Satellite Cell Development and Maintenance

Thu, 09/21/2017 - 00:00
In this article, Wiper-Bergeron and colleagues demonstrate that the transcription factor SOX7 is required for skeletal muscle satellite cell development and maintenance. SOX7 regulates Pax7 expression, and loss of SOX7 leads to fewer satellite cells that are more sensitive to apoptosis. Furthermore, loss of Sox7 in satellite cells results in smaller myotubes and impaired regeneration after injury in post-natal muscle.

Spindle Misorientation of Cerebral and Cerebellar Progenitors Is a Mechanistic Cause of Megalencephaly

Thu, 09/21/2017 - 00:00
Ploubidou and colleagues assess the impact of misorientation of the mitotic spindle of neuronal progenitor cells on brain development. They employ a spindle misorientation model expressing truncated RHAMM, exhibiting no centrosome biogenesis or spindle assembly defects in vivo. The data demonstrate that spindle misorientation in cerebellum and cerebrum neuroprogenitors results in megalencephaly and that RHAMM regulates differentiation in the developing brain.

Transfer of a Mouse Artificial Chromosome into Spermatogonial Stem Cells Generates Transchromosomic Mice

Thu, 09/21/2017 - 00:00
In this article, Kazuki and colleagues show that spermatogonial stem cells can maintain a minichromosome vector more stably than ESCs, which often undergo karyotype abnormalities and loss of minichromosomes during long-term culture. Because transchromosomic mice can be produced in F1 generation, this method overcomes problems associated with previous methods using ESCs and provides new possibilities for germline manipulation.

In Vivo Generation of Engraftable Murine Hematopoietic Stem Cells by Gfi1b, c-Fos, and Gata2 Overexpression within Teratoma

Thu, 09/21/2017 - 00:00
Tsukada et al. demonstrate that teratomas formed in vivo by Gfi1b-, c-Fos-, and Gata2-overexpressing iPSCs give rise to functional, long-term HSCs. Teratoma-derived HSCs and hematopoietic cells were detected in peripheral blood, expanded to the bone marrow after depletion of host HSCs, and showed successful engraftment in serial transplantation assays. This work underscores the importance of evaluating differentiation strategies in vivo.

Prolactin Alters the Mammary Epithelial Hierarchy, Increasing Progenitors and Facilitating Ovarian Steroid Action

Thu, 09/14/2017 - 00:00
Elevated prolactin correlates with increased risk for aggressive breast cancers expressing ERα. In a transgenic mouse model with high mammary prolactin, Schuler and colleagues demonstrate expanded progenitor/stem epithelial populations and impeded steroid-induced luminal cell maturation, associated with altered transcriptional networks to perturb differentiation, which may underlie its contributions to this disease.

Single-Cell Gene Expression Analysis of a Human ESC Model of Pancreatic Endocrine Development Reveals Different Paths to β-Cell Differentiation

Thu, 09/14/2017 - 00:00
In this article, Honoré, Grapin-Botton, and colleagues use single-cell expression profiling to show a differentiation sequence from hESCs to pancreatic endocrine cells and early divergence of paths to different endocrine subtypes. Two paths lead to β-cell differentiation where NKX6.1 can be initiated before or after endocrine commitment.

Top-Down Inhibition of BMP Signaling Enables Robust Induction of hPSCs Into Neural Crest in Fully Defined, Xeno-free Conditions

Thu, 09/14/2017 - 00:00
Hackland and colleagues have developed a method for the generation of human neural crest cells that allows their use in clinical applications. Their method allows for greater control over the environment of the cells by managing the influence of cell-produced signals, and this approach could be applied to other systems.

Ontogenic Identification and Analysis of Mesenchymal Stromal Cell Populations during Mouse Limb and Long Bone Development

Thu, 09/14/2017 - 00:00
In this article, Zeller and colleagues show that functionally distinct MSC populations arise at specific time points during mouse embryonic limb and long bone development and persist during homeostasis. In particular, a PαS subpopulation with the ability to form well-structured bone organoids encompassing functional endothelial and hematopoietic compartments is identified, which is of relevance for bone tissue engineering.

Blockage of the Epithelial-to-Mesenchymal Transition Is Required for Embryonic Stem Cell Derivation

Thu, 09/14/2017 - 00:00
In this article, Baharvand and colleagues provided a platform to discover influential genes and cellular events involved in transition from the ICM cells to embryonic stem cells (ESCs) by applying gene expression profiling from the ICM cells, various stages of ICM outgrowths, and early to further passages of ESCs.

PDGFRA Is Not Essential for the Derivation and Maintenance of Mouse Extraembryonic Endoderm Stem Cell Lines

Thu, 09/14/2017 - 00:00
Extraembryonic endoderm stem (XEN) cell lines can be derived and maintained in vitro and reflect the primitive endoderm lineage. Platelet-derived growth factor receptor alpha has been thought to be essential for the derivation and maintenance of mouse XEN cell lines. Mombaerts and colleagues have re-evaluated this requirement and conclude that it is not the case.

Directed Differentiation of Human Bone Marrow Stromal Cells to Fate-Committed Schwann Cells

Thu, 09/07/2017 - 00:00
Ying-Shing Chan and colleagues demonstrate that the human bone marrow harbors neuro-ectodermal progenitors that can be enriched, expanded, and directed to differentiate into functionally mature, fate-committed SCs. This work holds promise for further development into an autologous cell source for implantation as a treatment strategy for nerve injuries or peripheral neuropathies.

Single Stem Cell Imaging and Analysis Reveals Telomere Length Differences in Diseased Human and Mouse Skeletal Muscles

Thu, 09/07/2017 - 00:00
In this article, Mourkioti and colleagues develop a telomere assay named MuQ-FISH and show that the critical telomere shortening of muscle stem cells from boys with Duchenne muscular dystrophy contributes to the progressive dysfunction that compromises their regenerative potential.

A PITX3-EGFP Reporter Line Reveals Connectivity of Dopamine and Non-dopamine Neuronal Subtypes in Grafts Generated from Human Embryonic Stem Cells

Thu, 08/31/2017 - 00:00
Here, Niclis and colleagues have used a human Pitx3-GFP embryonic stem cell line to map patterns of connectivity of transplanted DA neurons in a rat model of Parkinson’s disease. The results show that stem cell-derived DA neuronal subtypes innervate developmentally appropriate targets but also that contemporary differentiation and transplantation procedures yield grafts with extensive patterns of non-DA growth.

Germline Stem Cell Activity Is Sustained by SALL4-Dependent Silencing of Distinct Tumor Suppressor Genes

Thu, 08/31/2017 - 00:00
In this article, Hobbs and colleagues characterize a critical role for the transcription factor SALL4 in maintenance of undifferentiated spermatogonia in the testis. While undifferentiated cells initially tolerated acute Sall4 deletion, they were progressively depleted over time. SALL4 regulated undifferentiated cell function by repressing Dusp4 and Foxl1, which suppressed cell proliferation and survival and blocked self-renewal signals when aberrantly expressed.

Functional Enterospheres Derived In Vitro from Human Pluripotent Stem Cells

Thu, 08/31/2017 - 00:00
Organoids derived from human pluripotent stem cells (hPSCs) represent an attractive system for investigating human development and disease in vitro. Nadkarni et al. show that hPSC-derived cystic intestinal organoids, or enterospheres, have a uniform epithelial structure, are easily accessible to genetic modification, and contain functional intestinal cell types that provide an in vitro modeling system for studying human gastrointestinal biology.

NK Cell Alloreactivity against KIR-Ligand-Mismatched HLA-Haploidentical Tissue Derived from HLA Haplotype-Homozygous iPSCs

Thu, 08/31/2017 - 00:00
In this article, Kawamoto and colleagues show that NK cells derived from an HLA-hetero individual killed the cells regenerated from HLA-homo iPSCs in KIR ligand-mismatched cases, by sensing the lack of KIR ligand expression. Such cytotoxicity was cancelled when regenerated cells are enforced to express the missing KIR ligand, providing a novel approach to prevent NK cell-mediated rejection.

Direct Reprogramming of Resident NG2 Glia into Neurons with Properties of Fast-Spiking Parvalbumin-Containing Interneurons

Thu, 08/24/2017 - 00:00
In this study, Parmar, Ottosson, and colleagues show how endogenous NG2 glia can be reprogrammed into GABAergic interneurons of different subtypes, the majority of them with properties of fast-spiking parvalbumin-containing interneurons. This neuronal subtype has been implicated in several neurological diseases, and the findings can open up new therapeutic options.