Archive | August 2015

The Isl1/Ldb1 Complex Orchestrates Genome-wide Chromatin Organization to Instruct Differentiation of Multipotent Cardiac Progenitors

Bhaskar Chanda Stem Cell Caputo et al. identify Ldb1 as a crucial regulator of cardiogenesis. Ldb1 binds the key cardiac transcription factor Isl1 and protects it from degradation. The stabilized Isl1/Ldb1 complex orchestrates a network for transcriptional regulation and coordination in three-dimensional space, driving cardiac progenitor cell differentiation and heart development.

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Genome-wide RNA-Seq of Human Motor Neurons Implicates Selective ER Stress Activation in Spinal Muscular Atrophy

Bhaskar Chanda Stem Cell Loss of the protein SMN causes spinal muscular atrophy, but it is unclear why deficiency in the ubiquitously expressed protein primarily affects motor neurons. In this study, Ng et al. show that a hyperactive ER stress pathway in SMA motor neurons could explain this selective neuronal vulnerability.

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Aberrant Lipid Metabolism in the Forebrain Niche Suppresses Adult Neural Stem Cell Proliferation in an Animal Model of Alzheimer’s Disease

Bhaskar Chanda Stem Cell Hamilton et al. identify deregulation of niche fatty acid metabolism as a mechanism of disease-induced stem cell impairment. They show that interfering with oleic acid signaling or synthesis rescues NSC proliferation in a mouse model of Alzheimer’s, revealing a potential approach to promote NSC-mediated brain function and repair.

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Rho-Signaling-Directed YAP/TAZ Activity Underlies the Long-Term Survival and Expansion of Human Embryonic Stem Cells

Bhaskar Chanda Stem Cell Ohgushi et al. show that a regulatory pathway involving Rho, YAP/TAZ, and the actin cytoskeleton that is specific for the pluripotent state enables human embryonic stem cells to undergo long-term survival and expansion in culture.

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Humanized Mice Reveal Differential Immunogenicity of Cells Derived from Autologous Induced Pluripotent Stem Cells

Bhaskar Chanda Stem Cell Patient iPSCs have potential as a renewable source for autologous cell therapy that avoids immune rejection. Using a humanized mouse model with a functional human immune system, Zhao et al. observe differential immune responses to various autologous hiPSC derivatives, including rejection of smooth muscle cells and tolerance to retinal pigmented epithelium.

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via Bhaskar Chanda UHN

Single-Cell RNA-Seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis

Bhaskar Chanda Stem Cell In vivo molecular dynamics of adult stem cells have been elusive. Shin et al. used single-cell RNA-seq and a novel bioinformatic approach named Waterfall to reconstruct somatic stem cell dynamics with unprecedented temporal resolution. The genome-wide molecular transitions they identified suggest commonalities among different somatic stem cell systems.

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Inflammation-Induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell-like Megakaryocyte Progenitors

Bhaskar Chanda Stem Cell Haas et al. show that inflammatory signaling activates post-transcriptional protein synthesis, maturation, and cell cycle induction in quiescent, but primed, stem-like megakaryocyte progenitors. This emergency program efficiently prevents otherwise life-threatening platelet depletion during acute inflammation.

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Human Neuropsychiatric Disease Modeling using Conditional Deletion Reveals Synaptic Transmission Defects Caused By Heterozygous Mutations in

Bhaskar Chanda Stem Cell Pak et al. show that introduction of a conditional mutation in a schizophrenia- and autism-associated gene enables precise functional analysis of neurons with a carefully controlled genetic background. Using this approach, they uncover haploinsufficiency phenotypes for human NRXN1, mimicking mutations seen in a range of neuropsychiatric disorders including schizophrenia.

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A TIM-3/Gal-9 Autocrine Stimulatory Loop Drives Self-Renewal of Human Myeloid Leukemia Stem Cells and Leukemic Progression

Bhaskar Chanda Stem Cell Signaling mechanisms specifically active in leukemic stem cells (LSCs) provide therapeutic opportunities. Akashi and colleagues identify a TIM-3/Gal-9 autocrine stimulatory loop that regulates self-renewal of human LSCs, through co-activation of NF-κB and β-catenin signaling, and promotes leukemic progression in a range of myeloid malignancies.

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via Bhaskar Chanda UHN