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Cell Stem Cell

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https://www.readbyqxmd.com/read/29129523/higher-order-kidney-organogenesis-from-pluripotent-stem-cells
#1
Atsuhiro Taguchi, Ryuichi Nishinakamura
Organogenesis generates higher-order structures containing functional subunits, connective components, and progenitor niches. Despite recent advances in organoid-based modeling of tissue development, recapitulating these complex configurations from pluripotent stem cells (PSCs) has remained challenging. In this study, we report assembly of kidney organoids that recapitulate embryonic branching morphogenesis. By studying the distinct origins and developmental processes of the ureteric bud, which contains epithelial kidney progenitors that undergo branching morphogenesis and thereby plays a central role in orchestrating organ geometry, and neighboring mesenchymal nephron progenitors, we established a protocol for differential induction of each lineage from mouse and human PSCs...
November 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28943028/engineering-ethics-and-self-organizing-models-of-human-development-opportunities-and-challenges
#2
Insoo Hyun
Incorporating engineering ethics early during the planning stages of organoid and gastruloid research may help prevent future confusion about the moral status of complex models of human development. However, the intrinsic self-organizing behavior of organoids and gastruloids may pose a slight challenge to this novel ethical approach.
September 12, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29100015/an-endosirna-based-repression-mechanism-counteracts-transposon-activation-during-global-dna-demethylation-in-embryonic-stem-cells
#3
Rebecca V Berrens, Simon Andrews, Dominik Spensberger, Fátima Santos, Wendy Dean, Poppy Gould, Jafar Sharif, Nelly Olova, Tamir Chandra, Haruhiko Koseki, Ferdinand von Meyenn, Wolf Reik
Erasure of DNA methylation and repressive chromatin marks in the mammalian germline leads to risk of transcriptional activation of transposable elements (TEs). Here, we used mouse embryonic stem cells (ESCs) to identify an endosiRNA-based mechanism involved in suppression of TE transcription. In ESCs with DNA demethylation induced by acute deletion of Dnmt1, we saw an increase in sense transcription at TEs, resulting in an abundance of sense/antisense transcripts leading to high levels of ARGONAUTE2 (AGO2)-bound small RNAs...
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29100014/tgf-%C3%AE-induced-quiescence-mediates-chemoresistance-of-tumor-propagating-cells-in-squamous-cell-carcinoma
#4
Jessie A Brown, Yoshiya Yonekubo, Nicole Hanson, Ana Sastre-Perona, Alice Basin, Julie A Rytlewski, Igor Dolgalev, Shane Meehan, Aristotelis Tsirigos, Slobodan Beronja, Markus Schober
Squamous cell carcinomas (SCCs) are heterogeneous tumors sustained by tumor-propagating cancer cells (TPCs). SCCs frequently resist chemotherapy through still unknown mechanisms. Here, we combine H2B-GFP-based pulse-chasing with cell-surface markers to distinguish quiescent from proliferative TPCs within SCCs. We find that quiescent TPCs resist DNA damage and exhibit increased tumorigenic potential in response to chemotherapy, whereas proliferative TPCs undergo apoptosis. Quiescence is regulated by TGF-β/SMAD signaling, which directly regulates cell-cycle gene transcription to control a reversible G1 cell-cycle arrest, independent of p21(CIP) function...
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29100013/long-range-gabaergic-inputs-regulate-neural-stem-cell-quiescence-and-control-adult-hippocampal-neurogenesis
#5
Hechen Bao, Brent Asrican, Weidong Li, Bin Gu, Zhexing Wen, Szu-Aun Lim, Issac Haniff, Charu Ramakrishnan, Karl Deisseroth, Benjamin Philpot, Juan Song
The quiescence of adult neural stem cells (NSCs) is regulated by local parvalbumin (PV) interneurons within the dentate gyrus (DG). Little is known about how local PV interneurons communicate with distal brain regions to regulate NSCs and hippocampal neurogenesis. Here, we identify GABAergic projection neurons from the medial septum (MS) as the major afferents to dentate PV interneurons. Surprisingly, dentate PV interneurons are depolarized by GABA signaling, which is in sharp contrast to most mature neurons hyperpolarized by GABA...
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29100012/targeting-glioma-stem-cell-derived-pericytes-disrupts-the-blood-tumor-barrier-and-improves-chemotherapeutic-efficacy
#6
Wenchao Zhou, Cong Chen, Yu Shi, Qiulian Wu, Ryan C Gimple, Xiaoguang Fang, Zhi Huang, Kui Zhai, Susan Q Ke, Yi-Fang Ping, Hua Feng, Jeremy N Rich, Jennifer S Yu, Shideng Bao, Xiu-Wu Bian
The blood-tumor barrier (BTB) is a major obstacle for drug delivery to malignant brain tumors such as glioblastoma (GBM). Disrupting the BTB is therefore highly desirable but complicated by the need to maintain the normal blood-brain barrier (BBB). Here we show that targeting glioma stem cell (GSC)-derived pericytes specifically disrupts the BTB and enhances drug effusion into brain tumors. We found that pericyte coverage of tumor vasculature is inversely correlated with GBM patient survival after chemotherapy...
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29100011/hematopoietic-stem-cell-gene-therapy-progress-and-lessons-learned
#7
REVIEW
Richard A Morgan, David Gray, Anastasia Lomova, Donald B Kohn
The use of allogeneic hematopoietic stem cells (HSCs) to treat genetic blood cell diseases has become a clinical standard but is limited by the availability of suitable matched donors and potential immunologic complications. Gene therapy using autologous HSCs should avoid these limitations and thus may be safer. Progressive improvements in techniques for genetic correction of HSCs, by either vector gene addition or gene editing, are facilitating successful treatments for an increasing number of diseases. We highlight the progress, successes, and remaining challenges toward the development of HSC gene therapies and discuss lessons they provide for the development of future clinical stem cell therapies...
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29100010/human-trials-of-stem-cell-derived-dopamine-neurons-for-parkinson-s-disease-dawn-of-a-new-era
#8
Roger A Barker, Malin Parmar, Lorenz Studer, Jun Takahashi
Stem cell-based therapies for Parkinson's disease are moving into a new and exciting era, with several groups pursuing clinical trials with pluripotent stem cell (PSC)-derived dopamine neurons. As many groups have ongoing or completed GMP-level cell manufacturing, we highlight key clinical translation considerations from our recent fourth GForce-PD meeting.
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29100009/emphasis-on-mutant-microglia-dysregulation-of-brain-sentinels-induces-neurodegeneration
#9
Bettina Schreiner, Melanie Greter
Reactive microglia are often implicated in the pathology of neurodegenerative disease. In a recent study in Nature, Mass et al. (2017) demonstrate that targeted mutation of Braf in early erythro-myeloid precursors (EMPs) causes histiocytosis-associated late onset neurodegeneration driven by activated microglia.
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29100008/at-last-gene-editing-in-human-embryos-to-understand-human-development
#10
Albert Ruzo, Ali H Brivanlou
Our understanding of early human development is typically based on inference from animal models, which may not fully recapitulate human embryonic features. As proof of concept, Fogarty et al. (2017) used CRISPR/Cas9 to genetically ablate the OCT4 gene in human preimplantation embryos and found key differences from its function in model systems.
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29100007/vitamin-c-c-ing-a-new-way-to-fight-leukemia
#11
Katharina Schönberger, Nina Cabezas-Wallscheid
Metabolic cues and (epi-)genetic factors are emerging regulators of hematopoietic stem cell (HSC) potency. Two new studies in Nature and Cell, from Agathocleous et al. (2017) and Cimmino et al. (2017), respectively, show that vitamin C regulates HSC function and suppresses leukemogenesis by modulating Tet2 activity.
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29100006/location-location-location-spatio-temporal-cues-that-define-the-cell-of-origin-in-melanoma
#12
Maria S Soengas, E Elizabeth Patton
It is unclear whether melanoma initiates from mature melanocytes or stem cell precursors. In this issue of Cell Stem Cell, Moon et al. (2017) and Köhler et al. (2017) use in vivo lineage tracing to demonstrate that these two possibilities may occur downstream of the same pro-tumorigenic lesions, depending on environmental factors or the anatomical location.
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29100005/neural-circuits-serve-as-periscopes-for-nscs
#13
Nannan Guo, Amar Sahay
Neural stem cells (NSCs) within the hippocampal niche integrate local cues, such as activity of inhibitory interneurons, into their homeostatic fate choices. Now in Cell Stem Cell, Bao et al. (2017) describe how these local interneurons relay signals from distal brain regions to govern NSC quiescence and activation.
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29033353/melanocyte-stem-cell-activation-and-translocation-initiate-cutaneous-melanoma-in-response-to-uv-exposure
#14
Hyeongsun Moon, Leanne R Donahue, Eunju Choi, Philip O Scumpia, William E Lowry, Jennifer K Grenier, Jerry Zhu, Andrew C White
Melanoma is one of the deadliest cancers, yet the cells of origin and mechanisms of tumor initiation remain unclear. The majority of melanomas emerge from clear skin without a precursor lesion, but it is unknown whether these melanomas can arise from melanocyte stem cells (MCSCs). Here we employ mouse models to define the role of MCSCs as melanoma cells of origin, demonstrate that MCSC quiescence acts as a tumor suppressor, and identify the extrinsic environmental and molecular factors required for the critical early steps of melanoma initiation...
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29033352/the-primate-specific-gene-tmem14b-marks-outer-radial-glia-cells-and-promotes-cortical-expansion-and-folding
#15
Jing Liu, Wensu Liu, Lu Yang, Qian Wu, Haofeng Zhang, Ai Fang, Long Li, Xiaohui Xu, Le Sun, Jun Zhang, Fuchou Tang, Xiaoqun Wang
Human brain evolution is associated with expansion and folding of the neocortex. Increased diversity in neural progenitor (NP) populations (such as basally located radial glia [RG], which reside in an enlarged outer subventricular zone [OSVZ]) likely contributes to this evolutionary expansion, although their characteristics and relative contributions are only partially understood. Through single-cell transcriptional profiling of sorted human NP subpopulations, we identified the primate-specific TMEM14B gene as a marker of basal RG...
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29033351/mouse-cutaneous-melanoma-induced-by-mutant-braf-arises-from-expansion-and-dedifferentiation-of-mature-pigmented-melanocytes
#16
Corinna Köhler, David Nittner, Florian Rambow, Enrico Radaelli, Fabio Stanchi, Niels Vandamme, Arianna Baggiolini, Lukas Sommer, Geert Berx, Joost J van den Oord, Holger Gerhardt, Cedric Blanpain, Jean-Christophe Marine
To identify the cells at the origin of melanoma, we combined single-cell lineage-tracing and transcriptomics approaches with time-lapse imaging. A mouse model that recapitulates key histopathological features of human melanomagenesis was created by inducing a BRafV600E-driven melanomagenic program in tail interfollicular melanocytes. Most targeted mature, melanin-producing melanocytes expanded clonally within the epidermis before losing their differentiated features through transcriptional reprogramming and eventually invading the dermis...
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28919367/nup153-interacts-with-sox2-to-enable-bimodal-gene-regulation-and-maintenance-of-neural-progenitor-cells
#17
Tomohisa Toda, Jonathan Y Hsu, Sara B Linker, Lauren Hu, Simon T Schafer, Jerome Mertens, Filipe V Jacinto, Martin W Hetzer, Fred H Gage
Neural progenitor cells (NeuPCs) possess a unique nuclear architecture that changes during differentiation. Nucleoporins are linked with cell-type-specific gene regulation, coupling physical changes in nuclear structure to transcriptional output; but, whether and how they coordinate with key fate-determining transcription factors is unclear. Here we show that the nucleoporin Nup153 interacts with Sox2 in adult NeuPCs, where it is indispensable for their maintenance and controls neuronal differentiation. Genome-wide analyses show that Nup153 and Sox2 bind and co-regulate hundreds of genes...
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28985529/multiplex-crispr-cas9-based-genome-editing-in-human-hematopoietic-stem-cells-models-clonal-hematopoiesis-and-myeloid-neoplasia
#18
Zuzana Tothova, John M Krill-Burger, Katerina D Popova, Catherine C Landers, Quinlan L Sievers, David Yudovich, Roger Belizaire, Jon C Aster, Elizabeth A Morgan, Aviad Tsherniak, Benjamin L Ebert
Hematologic malignancies are driven by combinations of genetic lesions that have been difficult to model in human cells. We used CRISPR/Cas9 genome engineering of primary adult and umbilical cord blood CD34(+) human hematopoietic stem and progenitor cells (HSPCs), the cells of origin for myeloid pre-malignant and malignant diseases, followed by transplantation into immunodeficient mice to generate genetic models of clonal hematopoiesis and neoplasia. Human hematopoietic cells bearing mutations in combinations of genes, including cohesin complex genes, observed in myeloid malignancies generated immunophenotypically defined neoplastic clones capable of long-term, multi-lineage reconstitution and serial transplantation...
October 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28985528/chromatin-and-single-cell-rna-seq-profiling-reveal-dynamic-signaling-and-metabolic-transitions-during-human-spermatogonial-stem-cell-development
#19
Jingtao Guo, Edward J Grow, Chongil Yi, Hana Mlcochova, Geoffrey J Maher, Cecilia Lindskog, Patrick J Murphy, Candice L Wike, Douglas T Carrell, Anne Goriely, James M Hotaling, Bradley R Cairns
Human adult spermatogonial stem cells (hSSCs) must balance self-renewal and differentiation. To understand how this is achieved, we profiled DNA methylation and open chromatin (ATAC-seq) in SSEA4(+) hSSCs, analyzed bulk and single-cell RNA transcriptomes (RNA-seq) in SSEA4(+) hSSCs and differentiating c-KIT(+) spermatogonia, and performed validation studies via immunofluorescence. First, DNA hypomethylation at embryonic developmental genes supports their epigenetic "poising" in hSSCs for future/embryonic expression, while core pluripotency genes (OCT4 and NANOG) were transcriptionally and epigenetically repressed...
October 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28985527/evolutionarily-distinctive-transcriptional-and-signaling-programs-drive-human-germ-cell-lineage-specification-from-pluripotent-stem-cells
#20
Yoji Kojima, Kotaro Sasaki, Shihori Yokobayashi, Yoshitake Sakai, Tomonori Nakamura, Yukihiro Yabuta, Fumio Nakaki, So Nagaoka, Knut Woltjen, Akitsu Hotta, Takuya Yamamoto, Mitinori Saitou
Germline specification underlies human reproduction and evolution, but it has proven difficult to study in humans since it occurs shortly after blastocyst implantation. This process can be modeled with human induced pluripotent stem cells (hiPSCs) by differentiating them into primordial germ cell-like cells (hPGCLCs) through an incipient mesoderm-like cell (iMeLC) state. Here, we elucidate the key transcription factors and their interactions with important signaling pathways in driving hPGCLC differentiation from iPSCs...
October 5, 2017: Cell Stem Cell
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