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Updated: 6 hours 28 min ago

A Critical Role of TET1/2 Proteins in Cell-Cycle Progression of Trophoblast Stem Cells

Thu, 03/22/2018 - 00:00
TET proteins are well known for their role in pluripotency. Here, Hemberger and colleagues show that TET1 and TET2 are also critical for maintaining the epithelial integrity of trophoblast stem cells. TET1/2 ensure mitotic cell-cycle progression by stabilizing cyclin B1 and by regulating centrosome organization. These insights reveal the importance of TET proteins beyond their role in epigenome remodeling.

Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development

Thu, 03/22/2018 - 00:00
Sances et al. combine Organ-Chip technology with human induced pluripotent stem cell-derived spinal motor neurons to study the maturation effects of Organ-Chip culture. By including microvascular cells also derived from the same patient line, the authors show enhancement of neuronal function, reproduction of vascular-neuron pathways, and specific gene activation that resembles in vivo spinal cord development.

A Humanized Mouse Model Generated Using Surplus Neonatal Tissue

Thu, 03/22/2018 - 00:00
Corresponding author William Burlingham and colleagues created a humanized mouse model called the NeoThy. The NeoThy uses human neonatal, rather than fetal, tissue sources for generating a human immune system within immunocompromised mouse hosts. NeoThy mice are an attractive alternative to conventional humanized mouse models, as they enable robust and reproducible iPSC immunogenicity experiments in vivo.

Retinal Ganglion Cell Diversity and Subtype Specification from Human Pluripotent Stem Cells

Thu, 03/22/2018 - 00:00
In this article, Langer and colleagues present extensive characterization of RGC subtypes derived from human pluripotent stem cells, with multiple subtypes identified by subtype-specific molecular markers. Their results present a more detailed analysis of RGC diversity in human cells and yield the use of different markers to identify RGC subtypes.

CD73 Regulates Stemness and Epithelial-Mesenchymal Transition in Ovarian Cancer-Initiating Cells

Thu, 03/15/2018 - 00:00
Cavallaro et al. characterized the transcriptome of OCIC-enriched primary cultures and found CD73 as an upregulated gene. CD73 was then shown to regulate the expression of stemness and EMT-associated genes. The expression and function of CD73 in OCICs is required for tumor initiation, and CD73-targeted drugs decrease the rate of tumor take and inhibit cancer growth.

UTX Affects Neural Stem Cell Proliferation and Differentiation through PTEN Signaling

Thu, 03/15/2018 - 00:00
In this article, Jiao and colleagues show that UTX is a critical regulator of neural progenitor cell proliferation and neurogenesis. When Utx is suppressed, the generation of neurons and terminal mitosis are affected. This study states that UTX controls the development of embryonic cortex through Pten in a sex-specific manner.

Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential

Tue, 03/13/2018 - 00:00
In the context of β cell replacement therapy for diabetes, de Koning and colleagues describe a 3D culture platform that supports ex vivo expansion of human pancreatic tissue as organoids. These organoids harbor a subpopulation of ALDHhi cells that display proliferative capacity and can differentiate to an endocrine fate.

KLF4 Nuclear Export Requires ERK Activation and Initiates Exit from Naive Pluripotency

Thu, 03/08/2018 - 00:00
Dhaliwal and colleagues show that KLF4 is exported from the nucleus to initiate embryonic stem cell differentiation. KLF4 nuclear export is caused by FGF-MEK-ERK signaling whereby activated ERK phosphorylates KLF4, allowing interaction with nuclear export factor Xportin1. Blocking KLF4 nuclear export prevents embryonic stem cell exit from naive pluripotency and slows development of the embryo.

miR-34b/c Regulates Wnt1 and Enhances Mesencephalic Dopaminergic Neuron Differentiation

Thu, 03/08/2018 - 00:00
In this article, Bellenchi and colleagues show that the microRNA miR-34b/c is expressed in FACS-purified Pitx3-GFP+ neurons and promotes dopaminergic differentiation by negative modulating Wnt1 and the downstream WNT signaling pathway. Induced dopaminergic cells, expressing miR-34b/c, synthesize dopamine and show the electrophysiological properties featured by brain dopaminergic neurons.

Gene Correction Reverses Ciliopathy and Photoreceptor Loss in iPSC-Derived Retinal Organoids from Retinitis Pigmentosa Patients

Thu, 03/08/2018 - 00:00
Jin and colleagues demonstrate that patient-specific iPSC-derived 3D retinae can recapitulate disease progress of retinitis pigmentosa through presenting defects in photoreceptor morphology, gene profile, and electrophysiology, as well as the defective ciliogenesis in iPSCs, iPSC-RPE, and 3D retinae. CRISPR/Cas9-mediated gene correction can rescue not only photoreceptor structure and electrophysiological property but also observed ciliopathy.

Combined Loss of JMJD1A and JMJD1B Reveals Critical Roles for H3K9 Demethylation in the Maintenance of Embryonic Stem Cells and Early Embryogenesis

Thu, 03/08/2018 - 00:00
Kuroki et al. showed that H3K9 demethylases JMJD1A and JMJD1B are redundantly but essentially required for ESC survival and early embryogenesis in mice. JMJD1A and JMJD1B ensure transcription accuracy by demethylating H3K9 at gene-dense euchromatin.

Modeling Down Syndrome with Patient iPSCs Reveals Cellular and Migration Deficits of GABAergic Neurons

Thu, 03/08/2018 - 00:00
In this article, Liu and colleagues show that Down syndrome iPSC-derived GABAergic interneurons exhibit less complexity in morphology and impaired migration both in vitro and in vivo.

YY1 Positively Regulates Transcription by Targeting Promoters and Super-Enhancers through the BAF Complex in Embryonic Stem Cells

Thu, 03/01/2018 - 00:00
In this article, Junjun Ding and colleagues show the role of YY1 in regulating embryonic stem cells through its interaction with OCT4 and the BAF complex to activate transcription, promote ESC proliferation, and maintain pluripotency, and the role of BAF complex in integrating YY1 into the core pluripotency network.

Neonatal Apex Resection Triggers Cardiomyocyte Proliferation, Neovascularization and Functional Recovery Despite Local Fibrosis

Thu, 03/01/2018 - 00:00
In this article, Nascimento and colleagues demonstrate that neonatal apex resection stimulates cardiomyocyte proliferation and permanent scarring in the apex. Newly formed cardiomyocytes compensate muscle loss by resection, and resected hearts recover functional competence in adulthood. These findings endorse this model for studies aiming to block cardiac fibrosis and/or favoring CM proliferation.

Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo

Thu, 03/01/2018 - 00:00
In this article, Van den Berg and colleagues show that PSC-derived kidney organoids contain nephron structures but remain disorganized and immature after prolonged culture. Upon transplantation, the organoids develop host-derived vascularization, functional glomerular perfusion, and connection to pre-existing vascular networks. The authors conclude that patent vasculature is required for ongoing morphogenesis and maturation of these kidney organoids.

Functional Beta Cell Mass from Device-Encapsulated hESC-Derived Pancreatic Endoderm Achieving Metabolic Control

Thu, 03/01/2018 - 00:00
In this article, Pipeleers and colleagues demonstrate that subcutaneous implants of device-encapsulated human stem cell-derived pancreatic endoderm can generate a functional beta cell mass that establishes sustained glucose control in mice. They identified their biologic characteristics and correlation with in vivo outcome. Data and methods are expected to guide clinical translation to beta cell replacement therapy in diabetes.

Contractile Work Contributes to Maturation of Energy Metabolism in hiPSC-Derived Cardiomyocytes

Thu, 03/01/2018 - 00:00
Ulmer et al. show that 3D-cultured human iPSC-derived cardiomyocytes replicate metabolic aspects of developmental hypertrophy, indicating maturation of hiPSC-derived cardiomyocytes.

Distinct Requirements for Extracellular and Intracellular MMP12 in the Development of the Adult V-SVZ Neural Stem Cell Niche

Thu, 03/01/2018 - 00:00
Shan et al. report that matrix metalloproteinase 12 (MMP12) is required for the appropriate development of the V-SVZ neural stem cell niche, with secreted MMP12 promoting niche organization and function, including the regulation of neural stem cell quiescence. An unexpected intracellular pool of a truncated yet functional MMP12 was also identified, which has a distinct role in promoting ependymal ciliogenesis.

Prospective Isolation of ISL1+ Cardiac Progenitors from Human ESCs for Myocardial Infarction Therapy

Thu, 03/01/2018 - 00:00
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.

BCL11B Drives Human Mammary Stem Cell Self-Renewal In Vitro by Inhibiting Basal Differentiation

Thu, 03/01/2018 - 00:00
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.