Bogeska, Ruzhica Mikecin, Ana-Matea Kaschutnig, Paul Fawaz, Malak Büchler-Schäff, Marleen Le, Duy Ganuza, Miguel Vollmer, Angelika Paffenholz, Stella V Asada, Noboru
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Cell stem cell
Hematopoietic stem cells (HSCs) mediate regeneration of the hematopoietic system following injury, such as following infection or inflammation. These challenges impair HSC function, but whether this functional impairment extends beyond the duration of inflammatory exposure is unknown. Unexpectedly, we observed an irreversible depletion of functiona...
Young, Jessica E Jayadev, Suman
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Cell stem cell
In this issue of Cell Stem Cell, Victor et al. reveal that human microglia harboring the Alzheimer's disease risk allele APOE4 have altered lipid metabolism and cellular activation. This dampens neuronal network activity, underscoring the importance of these brain-resident immune cells and highlighting a novel pathway for therapeutic intervention. ...
Burns, Sarah S Kapur, Reuben
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Cell stem cell
In the current issue of Cell Stem Cell, Bogeska et al. demonstrate that repeated exposures to inflammation cause indelible and specific functional compromise and accelerated aging of long-term hematopoietic stem cells (LT-HSCs). This study proposes the notion that the cumulative inflammatory events over the course of an organism's lifespan may irre...
Niec, Rachel E Chu, Tinyi Schernthanner, Marina Gur-Cohen, Shiri Hidalgo, Lynette Pasolli, Hilda Amalia Luckett, Kathleen A Wang, Zhong Bhalla, Sohni R Cambuli, Francesco
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Cell stem cell
Barrier epithelia depend upon resident stem cells for homeostasis, defense, and repair. Epithelial stem cells of small and large intestines (ISCs) respond to their local microenvironments (niches) to fulfill a continuous demand for tissue turnover. The complexity of these niches and underlying communication pathways are not fully known. Here, we re...
Ding, Shengli Hsu, Carolyn Wang, Zhaohui Natesh, Naveen R Millen, Rosemary Negrete, Marcos Giroux, Nicholas Rivera, Grecia O Dohlman, Anders Bose, Shree
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Cell stem cell
Patient-derived xenografts (PDXs) and patient-derived organoids (PDOs) have been shown to model clinical response to cancer therapy. However, it remains challenging to use these models to guide timely clinical decisions for cancer patients. Here, we used droplet emulsion microfluidics with temperature control and dead-volume minimization to rapidly...
Florez, Marcus A Tran, Brandon T Wathan, Trisha K DeGregori, James Pietras, Eric M King, Katherine Y
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Cell stem cell
Clonal hematopoiesis of indeterminate potential (CHIP) describes a widespread expansion of genetically variant hematopoietic cells that increases exponentially with age and is associated with increased risks of cancers, cardiovascular disease, and other maladies. Here, we discuss how environmental contexts associated with CHIP, such as old age, inf...
Kann, Allison P Hung, Margaret Wang, Wei Nguyen, Jo Gilbert, Penney M Wu, Zhuhao Krauss, Robert S
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Cell stem cell
Many tissues harbor quiescent stem cells that are activated upon injury, subsequently proliferating and differentiating to repair tissue damage. Mechanisms by which stem cells sense injury and transition from quiescence to activation, however, remain largely unknown. Resident skeletal muscle stem cells (MuSCs) are essential orchestrators of muscle ...
Capano, Lucia S Sato, Chihiro Ficulle, Elena Yu, Anan Horie, Kanta Kwon, Ji-Sun Burbach, Kyle F Barthélemy, Nicolas R Fox, Susan G Karch, Celeste M
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Cell stem cell
Tau is a microtubule-binding protein expressed in neurons, and the equal ratios between 4-repeat (4R) and 3-repeat (3R) isoforms are maintained in normal adult brain function. Dysregulation of 3R:4R ratio causes tauopathy, and human neurons that recapitulate tau isoforms in health and disease will provide a platform for elucidating pathogenic proce...
Roos, Floris J M van Tienderen, Gilles S Wu, Haoyu Bordeu, Ignacio Vinke, Dina Albarinos, Laura Muñoz Monfils, Kathryn Niesten, Sabrah Smits, Ron Willemse, Jorke
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Cell stem cell
Human cholangiocyte organoids show great promise for regenerative therapies and in vitro modeling of bile duct development and diseases. However, the cystic organoids lack the branching morphology of intrahepatic bile ducts (IHBDs). Here, we report establishing human branching cholangiocyte organoid (BRCO) cultures. BRCOs self-organize into complex...
Ma, Haiting de Zwaan, Esmée Guo, Yang Eric Cejas, Paloma Thiru, Prathapan van de Bunt, Martijn Jeppesen, Jacob F Syamala, Sudeepa Dall'Agnese, Alessandra Abraham, Brian J
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Cell stem cell
To understand the mechanisms regulating the in vitro maturation of hPSC-derived hepatocytes, we developed a 3D differentiation system and compared gene regulatory elements in human primary hepatocytes with those in hPSC-hepatocytes that were differentiated in 2D or 3D conditions by RNA-seq, ATAC-seq, and H3K27Ac ChIP-seq. Regulome comparisons showe...