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Cell Stem Cell

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https://www.readbyqxmd.com/read/29779890/high-throughput-screening-enhances-kidney-organoid-differentiation-from-human-pluripotent-stem-cells-and-enables-automated-multidimensional-phenotyping
#1
Stefan M Czerniecki, Nelly M Cruz, Jennifer L Harder, Rajasree Menon, James Annis, Edgar A Otto, Ramila E Gulieva, Laura V Islas, Yong Kyun Kim, Linh M Tran, Timothy J Martins, Jeffrey W Pippin, Hongxia Fu, Matthias Kretzler, Stuart J Shankland, Jonathan Himmelfarb, Randall T Moon, Neal Paragas, Benjamin S Freedman
Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and phenotyping of human kidney organoids. The entire 21-day protocol, from plating to differentiation to analysis, can be performed automatically by liquid-handling robots, or alternatively by manual pipetting...
May 15, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29779891/fixation-and-spread-of-somatic-mutations-in-adult-human-colonic-epithelium
#2
Anna M Nicholson, Cora Olpe, Alice Hoyle, Ann-Sofie Thorsen, Teja Rus, Mathilde Colombé, Roxanne Brunton-Sim, Richard Kemp, Kate Marks, Phil Quirke, Shalini Malhotra, Rogier Ten Hoopen, Ashraf Ibrahim, Cecilia Lindskog, Meagan B Myers, Barbara Parsons, Simon Tavaré, Mark Wilkinson, Edward Morrissey, Douglas J Winton
We investigated the means and timing by which mutations become fixed in the human colonic epithelium by visualizing somatic clones and mathematical inference. Fixation requires two sequential steps. First, one of approximately seven active stem cells residing within each colonic crypt has to be mutated. Second, the mutated stem cell has to replace neighbors to populate the entire crypt in a process that takes several years. Subsequent clonal expansion due to crypt fission is infrequent for neutral mutations (around 0...
May 11, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29779889/epithelial-sodium-channel-regulates-adult-neural-stem-cell-proliferation-in-a-flow-dependent-manner
#3
David Petrik, Michael H Myoga, Sofia Grade, Niklas J Gerkau, Melanie Pusch, Christine R Rose, Benedikt Grothe, Magdalena Götz
One hallmark of adult neurogenesis is its adaptability to environmental influences. Here, we uncovered the epithelial sodium channel (ENaC) as a key regulator of adult neurogenesis as its deletion in neural stem cells (NSCs) and their progeny in the murine subependymal zone (SEZ) strongly impairs their proliferation and neurogenic output in the olfactory bulb. Importantly, alteration of fluid flow promotes proliferation of SEZ cells in an ENaC-dependent manner, eliciting sodium and calcium signals that regulate proliferation via calcium-release-activated channels and phosphorylation of ERK...
May 9, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29754780/single-cell-transcriptomics-meets-lineage-tracing
#4
REVIEW
Lennart Kester, Alexander van Oudenaarden
Reconstructing lineage relationships between cells within a tissue or organism is a long-standing aim in biology. Traditionally, lineage tracing has been achieved through the (genetic) labeling of a cell followed by the tracking of its offspring. Currently, lineage trajectories can also be predicted using single-cell transcriptomics. Although single-cell transcriptomics provides detailed phenotypic information, the predicted lineage trajectories do not necessarily reflect genetic relationships. Recently, techniques have been developed that unite these strategies...
May 3, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29754779/a-linc1405-eomes-complex-promotes-cardiac-mesoderm-specification-and-cardiogenesis
#5
Xudong Guo, Yanxin Xu, Zikang Wang, Yukang Wu, Jiayu Chen, Guiying Wang, Chenqi Lu, Wenwen Jia, Jiajie Xi, Songcheng Zhu, Zeyidan Jiapaer, Xiaoping Wan, Zhongmin Liu, Shaorong Gao, Jiuhong Kang
Large intergenic non-coding RNAs (lincRNAs) play widespread roles in epigenetic regulation during multiple differentiation processes, but little is known about their mode of action in cardiac differentiation. Here, we identified the key roles of a lincRNA, termed linc1405, in modulating the core network of cardiac differentiation by functionally interacting with Eomes. Chromatin- and RNA-immunoprecipitation assays showed that exon 2 of linc1405 physically mediates a complex consisting of Eomes, trithorax group (TrxG) subunit WDR5, and histone acetyltransferase GCN5 binding at the enhancer region of Mesp1 gene and activates its expression during cardiac mesoderm specification of embryonic stem cells...
May 3, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29681515/the-dystrophin-glycoprotein-complex-regulates-the-epigenetic-activation-of-muscle-stem-cell-commitment
#6
Natasha C Chang, Marie-Claude Sincennes, Fabien P Chevalier, Caroline E Brun, Melanie Lacaria, Jessica Segalés, Pura Muñoz-Cánoves, Hong Ming, Michael A Rudnicki
Asymmetrically dividing muscle stem cells in skeletal muscle give rise to committed cells, where the myogenic determination factor Myf5 is transcriptionally activated by Pax7. This activation is dependent on Carm1, which methylates Pax7 on multiple arginine residues, to recruit the ASH2L:MLL1/2:WDR5:RBBP5 histone methyltransferase complex to the proximal promoter of Myf5. Here, we found that Carm1 is a specific substrate of p38γ/MAPK12 and that phosphorylation of Carm1 prevents its nuclear translocation...
April 19, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29681514/human-adult-neurogenesis-evidence-and-remaining-questions
#7
REVIEW
Gerd Kempermann, Fred H Gage, Ludwig Aigner, Hongjun Song, Maurice A Curtis, Sandrine Thuret, H Georg Kuhn, Sebastian Jessberger, Paul W Frankland, Heather A Cameron, Elizabeth Gould, Rene Hen, D Nora Abrous, Nicolas Toni, Alejandro F Schinder, Xinyu Zhao, Paul J Lucassen, Jonas Frisén
Renewed discussion about whether or not adult neurogenesis exists in the human hippocampus, and the nature and strength of the supporting evidence, has been reignited by two prominently published reports with opposite conclusions. Here, we summarize the state of the field and argue that there is currently no reason to abandon the idea that adult-generated neurons make important functional contributions to neural plasticity and cognition across the human lifespan.
April 18, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29656942/evolving-industry-partnerships-and-investments-in-cell-and-gene-therapies
#8
Devyn M Smith, Emily J Culme-Seymour, Chris Mason
Cell and gene therapies hold the promise of providing significant and durable health gains to patients in many disease states and have recently elicited significant investor and partner interest. We cover the current state of industry partnerships and investments, highlight what makes a partnership advantageous, and discuss implications for stem cell therapies.
April 12, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29656943/myoepithelial-cells-of-submucosal-glands-can-function-as-reserve-stem-cells-to-regenerate-airways-after-injury
#9
Aleksandra Tata, Yoshihiko Kobayashi, Ryan D Chow, Jasmine Tran, Avani Desai, Abdull J Massri, Timothy J McCord, Michael Dee Gunn, Purushothama Rao Tata
Cells demonstrate plasticity following injury, but the extent of this phenomenon and the cellular mechanisms involved remain underexplored. Using single-cell RNA sequencing (scRNA-seq) and lineage tracing, we uncover that myoepithelial cells (MECs) of the submucosal glands (SMGs) proliferate and migrate to repopulate the airway surface epithelium (SE) in multiple injury models. Specifically, SMG-derived cells display multipotency and contribute to basal and luminal cell types of the SMGs and SE. Ex vivo expanded MECs have the potential to repopulate and differentiate into SE cells when grafted onto denuded airway scaffolds...
April 7, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29681516/super-obese-patient-derived-ipsc-hypothalamic-neurons-exhibit-obesogenic-signatures-and-hormone-responses
#10
Uthra Rajamani, Andrew R Gross, Brooke E Hjelm, Adolfo Sequeira, Marquis P Vawter, Jie Tang, Vineela Gangalapudi, Yizhou Wang, Allen M Andres, Roberta A Gottlieb, Dhruv Sareen
The hypothalamus contains neurons that integrate hunger and satiety endocrine signals from the periphery and are implicated in the pathophysiology of obesity. The limited availability of human hypothalamic neurons hampers our understanding of obesity disease mechanisms. To address this, we generated human induced pluripotent stem cells (hiPSCs) from multiple normal body mass index (BMI; BMI ≤ 25) subjects and super-obese (OBS) donors (BMI ≥ 50) with polygenic coding variants in obesity-associated genes...
April 6, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29727685/submucosal-gland-myoepithelial-cells-are-reserve-stem-cells-that-can-regenerate-mouse-tracheal-epithelium
#11
Thomas J Lynch, Preston J Anderson, Pavana G Rotti, Scott R Tyler, Adrianne K Crooke, Soon H Choi, Daniel T Montoro, Carolyn L Silverman, Weam Shahin, Rui Zhao, Chandler W Jensen-Cody, Andrea Adamcakova-Dodd, T Idil Apak Evans, Weiliang Xie, Yulong Zhang, Hongmei Mou, B Paul Herring, Peter S Thorne, Jayaraj Rajagopal, Charles Yeaman, Kalpaj R Parekh, John F Engelhardt
No abstract text is available yet for this article.
May 3, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29727684/evolving-industry-partnerships-and-investments-in-cell-and-gene-therapies
#12
Devyn M Smith, Emily J Culme-Seymour, Chris Mason
No abstract text is available yet for this article.
May 3, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29727683/fasting-activates-fatty-acid-oxidation-to-enhance-intestinal-stem-cell-function-during-homeostasis-and-aging
#13
Maria M Mihaylova, Chia-Wei Cheng, Amanda Q Cao, Surya Tripathi, Miyeko D Mana, Khristian E Bauer-Rowe, Monther Abu-Remaileh, Laura Clavain, Aysegul Erdemir, Caroline A Lewis, Elizaveta Freinkman, Audrey S Dickey, Albert R La Spada, Yanmei Huang, George W Bell, Vikram Deshpande, Peter Carmeliet, Pekka Katajisto, David M Sabatini, Ömer H Yilmaz
Diet has a profound effect on tissue regeneration in diverse organisms, and low caloric states such as intermittent fasting have beneficial effects on organismal health and age-associated loss of tissue function. The role of adult stem and progenitor cells in responding to short-term fasting and whether such responses improve regeneration are not well studied. Here we show that a 24 hr fast augments intestinal stem cell (ISC) function in young and aged mice by inducing a fatty acid oxidation (FAO) program and that pharmacological activation of this program mimics many effects of fasting...
May 3, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29727682/retinoid-sensitive-epigenetic-regulation-of-the-hoxb-cluster-maintains-normal-hematopoiesis-and-inhibits-leukemogenesis
#14
Pengxu Qian, Bony De Kumar, Xi C He, Christof Nolte, Madelaine Gogol, Youngwook Ahn, Shiyuan Chen, Zhenrui Li, Hanzhang Xu, John M Perry, Deqing Hu, Fang Tao, Meng Zhao, Yingli Han, Kate Hall, Allison Peak, Ariel Paulson, Chongbei Zhao, Aparna Venkatraman, Andrew Box, Anoja Perera, Jeffrey S Haug, Tari Parmely, Hua Li, Robb Krumlauf, Linheng Li
Hox genes modulate the properties of hematopoietic stem cells (HSCs) and reacquired Hox expression in progenitors contributes to leukemogenesis. Here, our transcriptome and DNA methylome analyses revealed that Hoxb cluster and retinoid signaling genes are predominantly enriched in LT-HSCs, and this coordinate regulation of Hoxb expression is mediated by a retinoid-dependent cis-regulatory element, distal element RARE (DERARE). Deletion of the DERARE reduced Hoxb expression, resulting in changes to many downstream signaling pathways (e...
May 3, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29727681/prc1-fine-tunes-gene-repression-and-activation-to-safeguard-skin-development-and-stem-cell-specification
#15
Idan Cohen, Dejian Zhao, Carmit Bar, Victor J Valdes, Katherine L Dauber-Decker, Minh Binh Nguyen, Manabu Nakayama, Michael Rendl, Wendy A Bickmore, Haruhiko Koseki, Deyou Zheng, Elena Ezhkova
Polycomb repressive complexes (PRCs) 1 and 2 are essential chromatin regulators of cell identity. PRC1, a dominant executer of Polycomb-mediated control, functions as multiple sub-complexes that possess catalytic-dependent H2AK119 mono-ubiquitination (H2AK119ub) and catalytic-independent activities. Here, we show that, despite its well-established repressor functions, PRC1 binds to both silent and active genes. Through in vivo loss-of-function studies, we show that global PRC1 function is essential for skin development and stem cell (SC) specification, whereas PRC1 catalytic activity is dispensable...
May 3, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29727680/efficient-generation-of-ca3-neurons-from-human-pluripotent-stem-cells-enables-modeling-of-hippocampal-connectivity-in-vitro
#16
Anindita Sarkar, Arianna Mei, Apua C M Paquola, Shani Stern, Cedric Bardy, Jason R Klug, Stacy Kim, Neda Neshat, Hyung Joon Kim, Manching Ku, Maxim N Shokhirev, David H Adamowicz, Maria C Marchetto, Roberto Jappelli, Jennifer A Erwin, Krishnan Padmanabhan, Matthew Shtrahman, Xin Jin, Fred H Gage
Despite widespread interest in using human induced pluripotent stem cells (hiPSCs) in neurological disease modeling, a suitable model system to study human neuronal connectivity is lacking. Here, we report a comprehensive and efficient differentiation paradigm for hiPSCs that generate multiple CA3 pyramidal neuron subtypes as detected by single-cell RNA sequencing (RNA-seq). This differentiation paradigm exhibits characteristics of neuronal network maturation, and rabies virus tracing revealed synaptic connections between stem cell-derived dentate gyrus (DG) and CA3 neurons in vitro recapitulating the neuronal connectivity within the hippocampus...
May 3, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29727679/blood-development-hematopoietic-stem-cell-dependence-and-independence
#17
REVIEW
Elaine Dzierzak, Anna Bigas
Evidence of the diversity and multi-layered organization of the hematopoietic system is leading to new insights that may inform ex vivo production of blood cells. Interestingly, not all long-lived hematopoietic cells derive from hematopoietic stem cells (HSCs). Here we review the current knowledge on HSC-dependent cell lineages and HSC-independent tissue-resident hematopoietic cells and how they arise during embryonic development. Classical embryological and genetic experiments, cell fate tracing data, single-cell imaging, and transcriptomics studies provide information on the molecular/cell trajectories that form the complete hematopoietic system...
May 3, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29727678/causes-and-consequences-of-hematopoietic-stem-cell-heterogeneity
#18
REVIEW
Simon Haas, Andreas Trumpp, Michael D Milsom
Blood and immune cells derive from multipotent hematopoietic stem cells (HSCs). Classically, stem and progenitor populations have been considered discrete homogeneous populations. However, recent technological advances have revealed significant HSC heterogeneity, with evidence for early HSC lineage segregation and the presence of lineage-biased HSCs and lineage-restricted progenitors within the HSC compartment. These and other findings challenge many aspects of the classical view of HSC biology. We review the most recent findings regarding the causes and consequences of HSC heterogeneity, discuss their far-reaching implications, and suggest that so-called continuum-based models may help consolidate apparently divergent experimental observations in this field...
May 3, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29727677/the-lysosome-elixir-of-neural-stem-cell-youth
#19
Milos S Simic, Andrew Dillin
Recently in Science, Leeman et al. find that perturbing lysosomal activity of quiescent NSCs directly impedes their ability to become activated, similar to what happens during aging. Excitingly, they could rejuvenate old quiescent NSCs by enhancing the lysosome pathway, ameliorating their ability to clear protein aggregates and become activated.
May 3, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29727676/crinkle-cut-brain-organoids
#20
Madeline A Lancaster
In large mammalian brains, including those of humans, the surface of the cortex is highly folded. How these convolutions form is still unclear, but recent work in Nature Physics by Karzbrun et al. (2018) supports a mechanism involving differential surface swelling combined with internal constraint.
May 3, 2018: Cell Stem Cell
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