Archive | September 2016

Cystic Fibrosis Patients Benefit from Mini Guts

Bhaskar Chanda Stem Cell In a matter of years, organoid technology has gone from unraveling the basic science of intestinal stem cells to identifying effective treatments for cystic fibrosis patients in the Netherlands. This Profile describes how a collaboration between scientists, clinicians, health insurers, and biobanks is successfully applying organoid technology in personalized medicine.

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Mesenchymal Inflammation Drives Genotoxic Stress in Hematopoietic Stem Cells and Predicts Disease Evolution in Human Pre-leukemia

Bhaskar Chanda Stem Cell Cell-extrinsic factors driving malignant transformation remain understudied. In a mouse model of pre-leukemia, Zambetti and colleagues establish a concept of mesenchymal niche-induced genotoxic stress in hematopoietic stem cells through p53-S100A8/9-TLR4 signaling, with relevance to human leukemia. The findings provide conceptual and mechanistic insights into the link between inflammation and cancer.

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Transplanted Human Stem Cell-Derived Interneuron Precursors Mitigate Mouse Bladder Dysfunction and Central Neuropathic Pain after Spinal Cord Injury

Bhaskar Chanda Stem Cell Fandel et al. show that transplanted human ESC-derived interneuron precursors integrate into injured mouse spinal cord, differentiate into human GABAergic neurons, and relieve injury-related symptoms, such as neurogenic bladder dysfunction and central neuropathic pain.

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A Transient Developmental Hematopoietic Stem Cell Gives Rise to Innate-like B and T Cells

Bhaskar Chanda Stem Cell Beaudin and colleagues demonstrate the existence of a developmentally restricted hematopoietic stem cell with robust capability to generate innate-like lymphocytes. These data show that a population of rapidly proliferating fetal HSCs that extinguish prior to the establishment of adult hematopoiesis serve as the elusive cells of origin for layered immune development.

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Induction of Expandable Tissue-Specific Stem/Progenitor Cells through Transient Expression of YAP/TAZ

Bhaskar Chanda Stem Cell Reprogramming and lineage conversions have highlighted the plasticity of differentiated cell states. Here Panciera et al. build on these principles by showing that expression of YAP/TAZ can convert a range of differentiated cells into somatic stem cells of the same tissue, respecting lineage restrictions.

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DNA Damage-Induced HSPC Malfunction Depends on ROS Accumulation Downstream of IFN-1 Signaling and Bid Mobilization

Bhaskar Chanda Stem Cell Tasdogan et al. identify toxic levels of reactive oxygen species (ROS) as major culprit underlying HSPC malfunction in a mouse mutant with defective DNA repair. They further demonstrate that high ROS levels in HSPCs are dependent on DNA damage-associated IFN-1 signaling and the Bcl-2 homolog Bid.

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CD82 Is a Marker for Prospective Isolation of Human Muscle Satellite Cells and Is Linked to Muscular Dystrophies

Bhaskar Chanda Stem Cell In this article, Alexander, Rozkalne, and colleagues describe the identification of CD82 as a prospective marker for human muscle stem cells. Knockdown of CD82 in myogenic cells reduces myoblast proliferation and CD82 expression is reduced in dystrophic muscle stem cells, suggesting a link with muscle disease.

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Glycolytic Metabolism Plays a Functional Role in Regulating Human Pluripotent Stem Cell State

Bhaskar Chanda Stem Cell Gu et al. examine the associations between glycolytic metabolism and the pluripotency state of hESCs under different naive and primed growth conditions. They identify differences in the metabolic state and highlight potential metabolic approaches for regulating self-renewal and initial cell fate specification of hESCs.

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Functional Impairment in Miro Degradation and Mitophagy Is a Shared Feature in Familial and Sporadic Parkinson’s Disease

Bhaskar Chanda Stem Cell Using iPSC-derived neurons and other models, Hsieh et al. uncover a defect in clearance of damaged mitochondria in Parkinson’s disease. They show that in mutant cells, the mitochondrial outer membrane protein Miro is stabilized and remains on damaged mitochondria for longer than normal, prolonging active transport and inhibiting mitochondrial degradation.

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Adventitial MSC-like Cells Are Progenitors of Vascular Smooth Muscle Cells and Drive Vascular Calcification in Chronic Kidney Disease

Bhaskar Chanda Stem Cell Kramann et al. show that Gli1+ MSC-like cells that reside in the vascular wall differentiate into osteoblast-like cells after injury and make a major contribution to calcification. Ablation of these cells before injury eliminates calcification and therefore suggests that they could be a target for therapeutic intervention.

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