Archive | August 2016

MED12 Regulates HSC-Specific Enhancers Independently of Mediator Kinase Activity to Control Hematopoiesis

Bhaskar Chanda Stem Cell Aranda-Orgilles et al. show in vivo a cell-autonomous requirement of MED12 in the maintenance of hematopoietic stem cell function independent of CYCLIN C/CDK8. MED12 cooperates with P300 to preserve enhancer activity, and loss of MED12 causes H3K27Ac depletion at enhancers of essential HSC genes and failure of hematopoietic-specific transcriptional programs.

from Cell Stem Cell http://ift.tt/2blaWa5
via Bhaskar Chanda UHN

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RNA Splicing Modulation Selectively Impairs Leukemia Stem Cell Maintenance in Secondary Human AML

Bhaskar Chanda Stem Cell Crews et al. show that unique splice isoform signatures distinguish normal human HSC and progenitor cell aging from AML and MDS progenitors. Widespread deregulation of splicing factor gene expression typified AML progenitors and sensitized them to small-molecule splicing-targeted agents, supporting the utility of spliceosome modulation in leukemia stem cell eradication and anti-aging strategies.

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via Bhaskar Chanda UHN

3D Culture Supports Long-Term Expansion of Mouse and Human Nephrogenic Progenitors

Bhaskar Chanda Stem Cell Li et al. report the derivation and long-term culture of mouse and human nephron progenitor cell lines under chemically defined conditions in 3D format. Expanded NPCs have nephrogenic potential in vitro and in vivo and allow the study of kidney organogenesis, gene editing, drug screening, and disease modeling.

from Cell Stem Cell http://ift.tt/2bJwivJ
via Bhaskar Chanda UHN

Zika Virus Infects Neural Progenitors in the Adult Mouse Brain and Alters Proliferation

Bhaskar Chanda Stem Cell Li et al. show that peripheral ZIKV exposure in a mouse model can infect adult neural stem cells in the brain, leading to cell death and reduced proliferation. Thus, in addition to impacting fetal development, ZIKV infection may also have negative effects on the adult brain.

from Cell Stem Cell http://ift.tt/2bphV26
via Bhaskar Chanda UHN

Zika Virus Infects Neural Progenitors in the Adult Mouse Brain and Alters Proliferation

Bhaskar Chanda Stem Cell Li et al. show that peripheral ZIKV exposure in a mouse model can infect adult neural stem cells in the brain, leading to cell death and reduced proliferation. Thus, in addition to impacting fetal development, ZIKV infection may also have negative effects on the adult brain.

from Cell Stem Cell http://ift.tt/2bphV26
via Bhaskar Chanda UHN

Transcriptome Profiling of Patient-Specific Human iPSC-Cardiomyocytes Predicts Individual Drug Safety and Efficacy Responses In Vitro

Bhaskar Chanda Stem Cell hiPSC-CM transcriptome profiling showed greater inter-patient than intra-patient variation. Toxicology analysis predicted and functionally validated individualized drug responsiveness, suggesting that hiPSC-CMs could serve as preclinical readout platforms for precision medicine.

from Cell Stem Cell http://ift.tt/2b6UMy4
via Bhaskar Chanda UHN

Multipotency of Adult Hippocampal NSCs In Vivo Is Restricted by Drosha/NFIB

Bhaskar Chanda Stem Cell Rolando et al. investigated the function of the RNaseIII Drosha in the regulation of adult hippocampal stem cell maintenance and differentiation. They found that Drosha directly inhibits the expression of the transcription factor NFIB through a miRNA-independent mechanism, thereby permitting neurogenesis and preventing oligodendrocyte fate commitment.

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via Bhaskar Chanda UHN

Enhancing a Wnt-Telomere Feedback Loop Restores Intestinal Stem Cell Function in a Human Organotypic Model of Dyskeratosis Congenita

Bhaskar Chanda Stem Cell Using a human induced pluripotent stem cell-derived dyskeratosis congenita (DC) organotypic model, Woo and colleagues show that telomere shortening triggers abrogation of canonical Wnt signaling, resulting in defects in intestinal stem cell function. Restoring telomere capping and enhancing Wnt signaling can restore the Wnt-telomere feedback loop and rescue DC-associated intestinal dysfunction.

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via Bhaskar Chanda UHN

Zika Virus NS4A and NS4B Proteins Deregulate Akt-mTOR Signaling in Human Fetal Neural Stem Cells to Inhibit Neurogenesis and Induce Autophagy

Bhaskar Chanda Stem Cell Liang et al. show that after infection of human fetal neural stem cells, the ZIKV proteins NS4A and NS4B inhibit the Akt-mTOR signaling pathway, disrupting neurogenesis and inducing autophagy. Their study therefore identifies candidate molecular determinants of ZIKV pathogenesis and highlights potential targets for therapeutic intervention.

from Cell Stem Cell http://ift.tt/2baLTH1
via Bhaskar Chanda UHN

Zika Virus NS4A and NS4B Proteins Deregulate Akt-mTOR Signaling in Human Fetal Neural Stem Cells to Inhibit Neurogenesis and Induce Autophagy

Bhaskar Chanda Stem Cell Liang et al. show that after infection of human fetal neural stem cells, the ZIKV proteins NS4A and NS4B inhibit the Akt-mTOR signaling pathway, disrupting neurogenesis and inducing autophagy. Their study therefore identifies candidate molecular determinants of ZIKV pathogenesis and highlights potential targets for therapeutic intervention.

from Cell Stem Cell http://ift.tt/2baLTH1
via Bhaskar Chanda UHN