Single-Cell Transcriptomic Analyses of Cell Fate Transitions during Human Cardiac Reprogramming
Zhou et al. performed single-cell RNA sequencing to unravel molecular features of human cardiac reprogramming. They identified a “decision” point where cells either reprogram or regress to initial fate. Further, progression of reprogramming was quantitatively assessed by their developed “cell fate index,” which could be used for studying other biological processes.
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TNF-α Coordinates Hematopoietic Stem Cell Survival and Myeloid Regeneration
Passegué and colleagues reveal a complex role for TNF-α in hematopoietic regeneration. Inflammation-induced TNF-α eliminates myeloid progenitors but prevents HSC necroptosis and initiates emergency myelopoiesis through NF-κB-dependent mechanisms, hence promoting HSC survival and hematopoietic regeneration. Persistent TNF-α-driven hematopoietic regeneration underlies chronic inflammation and can contribute to aging and malignant hematopoiesis.
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Antibody Conditioning Enables MHC-Mismatched Hematopoietic Stem Cell Transplants and Organ Graft Tolerance
Treatment of hematological disorders via donor cell transplantation requires harsh and non-specific conditioning protocols. George et al. report an antibody-based conditioning protocol for HSC engraftment that does not require chemotherapy or irradiation and allows robust hematopoietic reconstitution even with fully mismatched MHC donor cells.
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Engineering Genetic Predisposition in Human Neuroepithelial Stem Cells Recapitulates Medulloblastoma Tumorigenesis
Huang, Tailor, et al. show that neuroepithelial stem (NES) cells derived from normal induced pluripotent stem cells (iPSCs) provide a renewable humancell-based resource to evaluate genetic mutations in medulloblastoma. Misexpression of MYCN in both otherwise-normal NES cells and PTCH1+/− NES cells derived from patients with Gorlin syndrome each generated medulloblastoma in mice.
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Harnessing Hematopoietic Stem Cell Low Intracellular Calcium Improves Their Maintenance In Vitro
Maintenance of blood stem cells in vitro remains challenging. Snoeck and colleagues show that blood stem cells are endowed with low intracellular calcium and that culture in low-calcium media enhances their maintenance, among others, through stabilization of TET enzymes, which are required for normal stem cell function.
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Lipid Deprivation Induces a Stable, Naive-to-Primed Intermediate State of Pluripotency in Human PSCs
The regulation of human naive pluripotency remains incompletely understood. Cornacchia et al. show that lipid-free culture conditions are sufficient to skew human pluripotent stem cells toward a naive-to-primed intermediate state via endogenous ERK inhibition. Transcriptomic analyses suggest that pluripotency regulation via de novo lipogenesis mimics in vivo regulation during pre-implantation development.
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Direct Reprogramming of Human Neurons Identifies MARCKSL1 as a Pathogenic Mediator of Valproic Acid-Induced Teratogenicity
Chanda et al. used reprogrammed human neurons to model the neurodevelopmental toxicity induced by prenatal exposure to valproic acid, a potent teratogenic compound. By analyzing different phases of neuronal maturation in vitro, the authors identified valproate-mediated cellular mechanisms that selectively impair neuronal properties at early developmental stages.
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Mir-17∼92 Confers Motor Neuron Subtype Differential Resistance to ALS-Associated Degeneration
Tung and Peng et al. reveal that early dysregulation of mir-17∼92/nuclear PTEN pathway confers differential vulnerability on limb-innervating motor neurons in SOD1-linked ALS. Overexpression of mir-17∼92 promotes MN survival in vitro, while an intrathecal gene therapy approach ameliorates motor deficits in a SOD1G93A mouse model and prolongs survival.
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Intracellular Ca2+ Homeostasis and Nuclear Export Mediate Exit from Naive Pluripotency
MacDougall et al. identify Ranbp3 and Atp2b1 as regulators of naive pluripotency exit. Intracellular Ca2+ levels decrease during exit, and increasing Ca2+ levels in combination with GSK3i or Tcf7l1−/− sustains self-renewal and pluripotency in the absence of inhibitors or LIF.
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The Adult Adrenal Cortex Undergoes Rapid Tissue Renewal in a Sex-Specific Manner
Evidence in both mice and humans indicates significant differences in the adrenal cortex biology of the opposite sex. Using genetic tools combined with hormonal treatments, Grabek et al. demonstrate that cell proliferation and cell recruitment from a capsular stem cell compartment are active in females but suppressed by androgens in male mice.
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YAP, but Not RSPO-LGR4/5, Signaling in Biliary Epithelial Cells Promotes a Ductular Reaction in Response to Liver Injury
Biliary epithelial cells are facultative liver stem cells that form a ductular reaction (DR) to support liver regeneration. Tchorz et al. show that YAP and mTORC1 signaling promote a DR and that, although LGR4/5-mediated WNT/β-catenin signaling is dispensable for this process, it is required for hepatocyte-mediated regeneration after liver injury.
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Single-Cell Analysis of the Liver Epithelium Reveals Dynamic Heterogeneity and an Essential Role for YAP in Homeostasis and Regeneration
The transcriptional landscape of the epithelium in healthy and regenerating murine livers was investigated, revealing a dynamically fluctuating and heterogeneous YAP transcriptional program. Further analysis uncovered YAP signaling dualism: it is essential in biliary epithelial cells for homeostatic maintenance and in hepatocytes for the regenerative response to injury.
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Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers
Hashimoto and colleagues show that reprogramming factors act in concert at cardiac regulatory elements to directly reprogram mouse fibroblasts into induced cardiac-like myocytes (iCLMs). Moreover, cardiac reprogramming is achieved by activation of endogenous cardiac enhancers that initiate a cardiogenic gene regulatory network.
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Targeting the RNA m6A Reader YTHDF2 Selectively Compromises Cancer Stem Cells in Acute Myeloid Leukemia
Elimination of cancer stem cells in acute myeloid leukemia (AML) while preserving hematopoiesis is a challenge in leukemia treatment. Paris et al. demonstrate that inactivation of the RNA m6A reader YTHDF2 increases the half-life of m6A-modified transcripts and specifically compromises cancer stem cells, highlighting YTHDF2 as an essential regulator of AML.
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Landmark study signals shift in thinking about stem cell differentiation (Thu, 20 Jun 2019)
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Dormant neural stem cells in fruit flies activate to generate new brain cells (Tue, 18 Jun 2019)
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3D printed tissues and organs without the scaffolding (Mon, 17 Jun 2019)
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Introduced a new paradigm of cell transplantation with scaffold microrobots (Mon, 17 Jun 2019)
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First blood-brain barrier chip using stem cells (Wed, 12 Jun 2019)
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Tissue engineering: The big picture on growing small intestines (Fri, 07 Jun 2019)
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Scientists recreate blood-brain barrier defect outside the body (Thu, 06 Jun 2019)
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Research sheds new light on how brain stem cells are activated (Thu, 06 Jun 2019)
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Breaking down pathological protein aggregates (Thu, 06 Jun 2019)
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Recreating embryonic conditions at break sites can help bones heal faster (Wed, 05 Jun 2019)
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Improved human brain organoids to boost neurological disease research (Wed, 05 Jun 2019)
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Novel insights into cholesterol regulation may lead to new therapies for heart disease (Tue, 04 Jun 2019)
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Killing the unkillable cancer cells (Tue, 04 Jun 2019)
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Researchers discover cells that change their identity during normal development (Tue, 04 Jun 2019)
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New genetic weapons challenge sickle cell disease (Mon, 03 Jun 2019)
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