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Cell Stem Cell

Luca Peruzzotti-Jametti, Joshua D Bernstock, Nunzio Vicario, Ana S H Costa, Chee Keong Kwok, Tommaso Leonardi, Lee M Booty, Iacopo Bicci, Beatrice Balzarotti, Giulio Volpe, Giulia Mallucci, Giulia Manferrari, Matteo Donegà, Nunzio Iraci, Alice Braga, John M Hallenbeck, Michael P Murphy, Frank Edenhofer, Christian Frezza, Stefano Pluchino
Neural stem cell (NSC) transplantation can influence immune responses and suppress inflammation in the CNS. Metabolites, such as succinate, modulate the phenotype and function of immune cells, but whether and how NSCs are also activated by such immunometabolites to control immunoreactivity and inflammatory responses is unclear. Here, we show that transplanted somatic and directly induced NSCs ameliorate chronic CNS inflammation by reducing succinate levels in the cerebrospinal fluid, thereby decreasing mononuclear phagocyte (MP) infiltration and secondary CNS damage...
February 14, 2018: Cell Stem Cell
Nigel G Kooreman, Youngkyun Kim, Patricia E de Almeida, Vittavat Termglinchan, Sebastian Diecke, Ning-Yi Shao, Tzu-Tang Wei, Hyoju Yi, Devaveena Dey, Raman Nelakanti, Thomas P Brouwer, David T Paik, Idit Sagiv-Barfi, Arnold Han, Paul H A Quax, Jaap F Hamming, Ronald Levy, Mark M Davis, Joseph C Wu
Cancer cells and embryonic tissues share a number of cellular and molecular properties, suggesting that induced pluripotent stem cells (iPSCs) may be harnessed to elicit anti-tumor responses in cancer vaccines. RNA sequencing revealed that human and murine iPSCs express tumor-associated antigens, and we show here a proof of principle for using irradiated iPSCs in autologous anti-tumor vaccines. In a prophylactic setting, iPSC vaccines prevent tumor growth in syngeneic murine breast cancer, mesothelioma, and melanoma models...
February 8, 2018: Cell Stem Cell
Yuichi Hirata, Kazuhiro Furuhashi, Hiroshi Ishii, Hao Wei Li, Sandra Pinho, Lei Ding, Simon C Robson, Paul S Frenette, Joji Fujisaki
A crucial player in immune regulation, FoxP3+ regulatory T cells (Tregs) are drawing attention for their heterogeneity and noncanonical functions. Here, we describe a Treg subpopulation that controls hematopoietic stem cell (HSC) quiescence and engraftment. These Tregs highly expressed an HSC marker, CD150, and localized within the HSC niche in the bone marrow (BM). Specific reduction of BM Tregs achieved by conditional deletion of CXCR4 in Tregs increased HSC numbers in the BM. Adenosine generated via the CD39 cell surface ectoenzyme on niche Tregs protected HSCs from oxidative stress and maintained HSC quiescence...
February 7, 2018: Cell Stem Cell
Claudia Loebel, Jason A Burdick
Stem cells and tissue-derived stromal cells stimulate the repair of degenerated and injured tissues, motivating a growing number of cell-based interventions in the musculoskeletal field. Recent investigations have indicated that these cells are critical for their trophic and immunomodulatory role in controlling endogenous cells. This Review presents recent clinical advances where stem cells and stromal cells have been used to stimulate musculoskeletal tissue repair, including delivery strategies to improve cell viability and retention...
February 6, 2018: Cell Stem Cell
Julie Steffann, Pierre Jouannet, Jean-Paul Bonnefont, Hervé Chneiweiss, Nelly Frydman
No abstract text is available yet for this article.
February 2, 2018: Cell Stem Cell
Taku Wakabayashi, Hisamichi Naito, Jun-Ichi Suehiro, Yang Lin, Hideya Kawaji, Tomohiro Iba, Tsukasa Kouno, Sachi Ishikawa-Kato, Masaaki Furuno, Kazuhiro Takara, Fumitaka Muramatsu, Jia Weizhen, Hiroyasu Kidoya, Katsuhiko Ishihara, Yoshihide Hayashizaki, Kohji Nishida, Mervin C Yoder, Nobuyuki Takakura
The generation of new blood vessels via angiogenesis is critical for meeting tissue oxygen demands. A role for adult stem cells in this process remains unclear. Here, we identified CD157 (bst1, bone marrow stromal antigen 1) as a marker of tissue-resident vascular endothelial stem cells (VESCs) in large arteries and veins of numerous mouse organs. Single CD157+ VESCs form colonies in vitro and generate donor-derived portal vein, sinusoids, and central vein endothelial cells upon transplantation in the liver...
February 1, 2018: Cell Stem Cell
Peng Liu, Meng Chen, Yanxia Liu, Lei S Qi, Sheng Ding
Generation of induced pluripotent stem cells typically requires the ectopic expression of transcription factors to reactivate the pluripotency network. However, it remains largely unclear what remodeling events on endogenous chromatin trigger reprogramming toward induced pluripotent stem cells (iPSCs). Toward this end, we employed CRISPR activation to precisely target and remodel endogenous gene loci of Oct4 and Sox2. Interestingly, we found that single-locus targeting of Sox2 was sufficient to remodel and activate Sox2, which was followed by the induction of other pluripotent genes and establishment of the pluripotency network...
January 9, 2018: Cell Stem Cell
Rene C Adam, Hanseul Yang, Yejing Ge, Wen-Hui Lien, Ping Wang, Yilin Zhao, Lisa Polak, John Levorse, Sanjeethan C Baksh, Deyou Zheng, Elaine Fuchs
Tissue regeneration relies on resident stem cells (SCs), whose activity and lineage choices are influenced by the microenvironment. Exploiting the synchronized, cyclical bouts of tissue regeneration in hair follicles (HFs), we investigate how microenvironment dynamics shape the emergence of stem cell lineages. Employing epigenetic and ChIP-seq profiling, we uncover how signal-dependent transcription factors couple spatiotemporal cues to chromatin dynamics, thereby choreographing stem cell lineages. Using enhancer-driven reporters, mutagenesis, and genetics, we show that simultaneous BMP-inhibitory and WNT signals set the stage for lineage choices by establishing chromatin platforms permissive for diversification...
January 9, 2018: Cell Stem Cell
Zheng Wang, Micah D Gearhart, Yu-Wei Lee, Ishan Kumar, Bulat Ramazanov, Yan Zhang, Charles Hernandez, Alice Y Lu, Nils Neuenkirchen, Jingjing Deng, Jiaqi Jin, Yuval Kluger, Thomas A Neubert, Vivian J Bardwell, Natalia B Ivanova
Polycomb group proteins regulate self-renewal and differentiation in many stem cell systems. When assembled into two canonical complexes, PRC1 and PRC2, they sequentially deposit H3K27me3 and H2AK119ub histone marks and establish repressive chromatin, referred to as Polycomb domains. Non-canonical PRC1 complexes retain RING1/RNF2 E3-ubiquitin ligases but have unique sets of accessory subunits. How these non-canonical complexes recognize and regulate their gene targets remains poorly understood. Here, we show that the BCL6 co-repressor (BCOR), a member of the PRC1...
January 8, 2018: Cell Stem Cell
Shinya Sugimoto, Yuki Ohta, Masayuki Fujii, Mami Matano, Mariko Shimokawa, Kosaku Nanki, Shoichi Date, Shingo Nishikori, Yoshihiro Nakazato, Tetsuya Nakamura, Takanori Kanai, Toshiro Sato
Genetic lineage tracing has revealed that Lgr5+ murine colon stem cells (CoSCs) rapidly proliferate at the crypt bottom. However, the spatiotemporal dynamics of human CoSCs in vivo have remained experimentally intractable. Here we established an orthotopic xenograft system for normal human colon organoids, enabling stable reconstruction of the human colon epithelium in vivo. Xenografted organoids were prone to displacement by the remaining murine crypts, and this could be overcome by complete removal of the mouse epithelium...
December 21, 2017: Cell Stem Cell
Jaecheol Lee, Ning-Yi Shao, David T Paik, Haodi Wu, Hongchao Guo, Vittavat Termglinchan, Jared M Churko, Youngkyun Kim, Tomoya Kitani, Ming-Tao Zhao, Yue Zhang, Kitchener D Wilson, Ioannis Karakikes, Michael P Snyder, Joseph C Wu
Cardiac development requires coordinated and large-scale rearrangements of the epigenome. The roles and precise mechanisms through which specific epigenetic modifying enzymes control cardiac lineage specification, however, remain unclear. Here we show that the H3K4 methyltransferase SETD7 controls cardiac differentiation by reading H3K36 marks independently of its enzymatic activity. Through chromatin immunoprecipitation sequencing (ChIP-seq), we found that SETD7 targets distinct sets of genes to drive their stage-specific expression during cardiomyocyte differentiation...
March 1, 2018: Cell Stem Cell
Madeline N Hayes, Karin McCarthy, Alexander Jin, Mariana L Oliveira, Sowmya Iyer, Sara P Garcia, Sivasish Sindiri, Berkley Gryder, Zainab Motala, G Petur Nielsen, Jean-Paul Borg, Matt van de Rijn, David Malkin, Javed Khan, Myron S Ignatius, David M Langenau
Tumor growth and relapse are driven by tumor propagating cells (TPCs). However, mechanisms regulating TPC fate choices, maintenance, and self-renewal are not fully understood. Here, we show that Van Gogh-like 2 (Vangl2), a core regulator of the non-canonical Wnt/planar cell polarity (Wnt/PCP) pathway, affects TPC self-renewal in rhabdomyosarcoma (RMS)-a pediatric cancer of muscle. VANGL2 is expressed in a majority of human RMS and within early mononuclear progenitor cells. VANGL2 depletion inhibited cell proliferation, reduced TPC numbers, and induced differentiation of human RMS in vitro and in mouse xenografts...
March 1, 2018: Cell Stem Cell
Aydan Bulut-Karslioglu, Trisha A Macrae, Juan A Oses-Prieto, Sergio Covarrubias, Michelle Percharde, Gregory Ku, Aaron Diaz, Michael T McManus, Alma L Burlingame, Miguel Ramalho-Santos
A permissive chromatin environment coupled to hypertranscription drives the rapid proliferation of embryonic stem cells (ESCs) and peri-implantation embryos. We carried out a genome-wide screen to systematically dissect the regulation of the euchromatic state of ESCs. The results revealed that cellular growth pathways, most prominently translation, perpetuate the euchromatic state and hypertranscription of ESCs. Acute inhibition of translation rapidly depletes euchromatic marks in mouse ESCs and blastocysts, concurrent with delocalization of RNA polymerase II and reduction in nascent transcription...
March 1, 2018: Cell Stem Cell
H-H Greco Song, Rowza T Rumma, C Keith Ozaki, Elazer R Edelman, Christopher S Chen
Although the clinical demand for bioengineered blood vessels continues to rise, current options for vascular conduits remain limited. The synergistic combination of emerging advances in tissue fabrication and stem cell engineering promises new strategies for engineering autologous blood vessels that recapitulate not only the mechanical properties of native vessels but also their biological function. Here we explore recent bioengineering advances in creating functional blood macro and microvessels, particularly featuring stem cells as a seed source...
March 1, 2018: Cell Stem Cell
Kacey Ronaldson-Bouchard, Gordana Vunjak-Novakovic
Organs-on-a-chip (OOCs) are miniature tissues and organs grown in vitro that enable modeling of human physiology and disease. The technology has emerged from converging advances in tissue engineering, semiconductor fabrication, and human cell sourcing. Encompassing innovations in human stem cell technology, OOCs offer a promising approach to emulate human patho/physiology in vitro, and address limitations of current cell and animal models. Here, we review the design considerations for single and multi-organ OOCs, discuss remaining challenges, and highlight the potential impact of OOCs as a fast-track opportunity for tissue engineering to advance drug development and precision medicine...
March 1, 2018: Cell Stem Cell
Thomas A Rando, Fabrisia Ambrosio
The emerging field of regenerative rehabilitation integrates biological and bioengineering advances in regenerative medicine with rehabilitative sciences. Here we highlight recent stem cell-based examples of the regenerative rehabilitation paradigm to promote tissue repair and regeneration, and we discuss remaining challenges and future directions for the field.
March 1, 2018: Cell Stem Cell
Laura E Niklason
The extracellular matrix is a biologically critical entity that has historically been poorly understood. Here we discuss how new tools for characterizing matrix composition and function enable us to design and deliver advanced matrices in vitro, to optimize regeneration, and in vivo, within a variety of tissues and organs.
March 1, 2018: Cell Stem Cell
Paul E Bourgine, Ivan Martin, Timm Schroeder
Recent advances in engineering complex organs in vitro inspire the development of human bone marrow equivalents to foster scientific discovery and innovative therapeutics. Here, we discuss challenges in generating relevant human bone marrow proxies, potential design principles, and future directions.
March 1, 2018: Cell Stem Cell
Kelly R Stevens, Charles E Murry
The combined power of human pluripotent stem cells and tissue engineering promises to revolutionize medicine by building tissue patches and artificial replacement organs for patients battling diverse diseases. Here, we articulate some big questions that need to be addressed before such engineered tissues become mainstream in the clinic.
March 1, 2018: Cell Stem Cell
Senthil K Muthuswamy
Organoids have tremendous promise for modeling human cancers and revealing new biological insights. Sachs et al. (2018), Seino et al. (2018) (in this issue of Cell Stem Cell), and Broutier et al. (2017) derive cancer organoids from breast, pancreas, and liver, respectively, not only reporting new methodologies but also showing their utility for translational and clinical cancer research.
March 1, 2018: Cell Stem Cell
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