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Stem Cell Reports

Anneliis Ihermann-Hella, Tsuyoshi Hirashima, Jussi Kupari, Kristen Kurtzeborn, Hao Li, Hyuk Nam Kwon, Cristina Cebrian, Abdul Soofi, Arvydas Dapkunas, Ilkka Miinalainen, Gregory R Dressler, Michiyuki Matsuda, Satu Kuure
The in vivo niche and basic cellular properties of nephron progenitors are poorly described. Here we studied the cellular organization and function of the MAPK/ERK pathway in nephron progenitors. Live-imaging of ERK activity by a Förster resonance energy transfer biosensor revealed a dynamic activation pattern in progenitors, whereas differentiating precursors exhibited sustained activity. Genetic experiments demonstrate that MAPK/ERK activity controls the thickness, coherence, and integrity of the nephron progenitor niche...
September 10, 2018: Stem Cell Reports
Tereza Renzova, Dasa Bohaciakova, Milan Esner, Veronika Pospisilova, Tomas Barta, Ales Hampl, Lukas Cajanek
Centrioles account for centrosomes and cilia formation. Recently, a link between centrosomal components and human developmental disorders has been established. However, the exact mechanisms how centrosome abnormalities influence embryogenesis and cell fate are not understood. PLK4-STIL module represents a key element of centrosome duplication cycle. We analyzed consequences of inactivation of the module for early events of embryogenesis in human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs)...
August 30, 2018: Stem Cell Reports
Andrew R Yale, Jamison L Nourse, Kayla R Lee, Syed N Ahmed, Janahan Arulmoli, Alan Y L Jiang, Lisa P McDonnell, Giovanni A Botten, Abraham P Lee, Edwin S Monuki, Michael Demetriou, Lisa A Flanagan
Understanding the cellular properties controlling neural stem and progenitor cell (NSPC) fate choice will improve their therapeutic potential. The electrophysiological measure whole-cell membrane capacitance reflects fate bias in the neural lineage but the cellular properties underlying membrane capacitance are poorly understood. We tested the hypothesis that cell surface carbohydrates contribute to NSPC membrane capacitance and fate. We found NSPCs differing in fate potential express distinct patterns of glycosylation enzymes...
August 29, 2018: Stem Cell Reports
Mari-Liis Kauts, Bianca De Leo, Carmen Rodríguez-Seoane, Roger Ronn, Fokion Glykofrydis, Antonio Maglitto, Polynikis Kaimakis, Margarita Basi, Helen Taylor, Lesley Forrester, Adam C Wilkinson, Berthold Göttgens, Philippa Saunders, Elaine Dzierzak
Mast cells are tissue-resident immune cells. Their overgrowth/overactivation results in a range of common distressing, sometimes life-threatening disorders, including asthma, psoriasis, anaphylaxis, and mastocytosis. Currently, drug discovery is hampered by use of cancer-derived mast cell lines or primary cells. Cell lines provide low numbers of mature mast cells and are not representative of in vivo mast cells. Mast cell generation from blood/bone marrow gives poor reproducibility, requiring 8-12 weeks of culture...
August 29, 2018: Stem Cell Reports
Takahisa Matsuzaki, Shinya Matsumoto, Toshiharu Kasai, Emi Yoshizawa, Satoshi Okamoto, Hiroshi Y Yoshikawa, Hideki Taniguchi, Takanori Takebe
Cellular membrane fluidity is a critical modulator of cell adhesion and migration, prompting us to define the systematic landscape of lineage-specific cellular fluidity throughout differentiation. Here, we have unveiled membrane fluidity landscapes in various lineages ranging from human pluripotency to differentiated progeny: (1) membrane rigidification precedes the exit from pluripotency, (2) membrane composition modulates activin signaling transmission, and (3) signatures are relatively germ layer specific presumably due to unique lipid compositions...
August 29, 2018: Stem Cell Reports
Hiromi Kumamaru, Paul Lu, Ephron S Rosenzweig, Mark H Tuszynski
Axonal regeneration after spinal cord injury (SCI) can be enhanced by activation of the intrinsic neuronal growth state and, separately, by placement of growth-enabling neural progenitor cell (NPC) grafts into lesion sites. Indeed, NPC grafts support regeneration of all host axonal projections innervating the normal spinal cord. However, some host axons regenerate only short distances into grafts. We examined whether activation of the growth state of the host injured neuron would elicit greater regeneration into NPC grafts...
August 28, 2018: Stem Cell Reports
Jordi Senserrich, Antoniana Batsivari, Stanislav Rybtsov, Sabrina Gordon-Keylock, Celine Souilhol, Frank Buchholz, David Hills, Suling Zhao, Alexander Medvinsky
Hematopoietic stem cells (HSCs) develop in the embryonic aorta-gonad-mesonephros (AGM) region and subsequently relocate to fetal liver. Runx1 transcription factor is essential for HSC development, but is largely dispensable for adult HSCs. Here, we studied tamoxifen-inducible Runx1 inactivation in vivo. Induction at pre-liver stages (up to embryonic day 10.5) reduced erythromyeloid progenitor numbers, but surprisingly did not block the appearance of Runx1-null HSCs in liver. By contrast, ex vivo analysis showed an absolute Runx1 dependency of HSC development in the AGM region...
September 11, 2018: Stem Cell Reports
(no author information available yet)
Female scientists play important leadership roles in the field and with the International Society for Stem Cell Research. We asked a number of these top researchers to share their personal stories and reflect on their career paths. Part II of this series will run in the October 2018 issue of Stem Cell Reports.
September 11, 2018: Stem Cell Reports
Marco Terrigno, Michele Bertacchi, Luca Pandolfini, Mario Baumgart, Mariantonietta Calvello, Alessandro Cellerino, Michèle Studer, Federico Cremisi
The morphogen FGF8 plays a pivotal role in neocortical area patterning through its inhibitory effect on COUP-TFI/Nr2f1 anterior expression, but its mechanism of action is poorly understood. We established an in vitro model of mouse embryonic stem cell corticogenesis in which COUP-TFI protein expression is inhibited by the activation of FGF8 in a time window corresponding to cortical area patterning. Interestingly, overexpression of the COUP-TFI 3'UTR reduces the inhibitory effect of FGF8 on COUP-TFI translation...
September 11, 2018: Stem Cell Reports
Menghua Wu, Da Zhang, Chunying Bi, Tingwei Mi, Wenliang Zhu, Longkuo Xia, Zhaoqian Teng, Baoyang Hu, Yihui Wu
Differentiation of human pluripotent stem cells (hPSCs) into striatal medium spiny neurons (MSNs) promises a cell-based therapy for Huntington's disease. However, clinical-grade MSNs remain unavailable. Here, we developed a chemical recipe named XLSBA to generate clinical-grade MSNs from embryonic stem cells (ESCs). We introduced the γ-secretase inhibitor DAPT into the recipe to accelerate neural differentiation, and replaced protein components with small molecules. Using this optimized protocol we could efficiently direct regular human ESCs (hESCs) as well as clinical-grade hESCs to lateral ganglionic eminence (LGE)-like progenitors and striatal MSNs within less than half of the time than previous protocols (within 14 days and 21 days, respectively)...
September 11, 2018: Stem Cell Reports
Shunsuke Tanigawa, Mazharul Islam, Sazia Sharmin, Hidekazu Naganuma, Yasuhiro Yoshimura, Fahim Haque, Takumi Era, Hitoshi Nakazato, Koichi Nakanishi, Tetsushi Sakuma, Takashi Yamamoto, Hidetake Kurihara, Atsuhiro Taguchi, Ryuichi Nishinakamura
Mutations in the NPHS1 gene, which encodes NEPHRIN, cause congenital nephrotic syndrome, resulting from impaired slit diaphragm (SD) formation in glomerular podocytes. However, methods for SD reconstitution have been unavailable, thereby limiting studies in the field. In the present study, we established human induced pluripotent stem cells (iPSCs) from a patient with an NPHS1 missense mutation, and reproduced the SD formation process using iPSC-derived kidney organoids. The mutant NEPHRIN failed to become localized on the cell surface for pre-SD domain formation in the induced podocytes...
September 11, 2018: Stem Cell Reports
Stefan Zweifel, Guillaume Marcy, Quentin Lo Guidice, Deqiang Li, Christophe Heinrich, Kasum Azim, Olivier Raineteau
The largest diversity of neural lineages generated from the subventricular zone (SVZ) occurs early after birth and is regulated in a spatiotemporal manner depending on the expression of specific transcriptional cues. Transcriptomics and fate-mapping approaches were employed to explore the relationship between regional expression of transcription factors by neural stem cells (NSCs) and the specification of distinct neural lineages. Our results support an early priming of NSCs for the genesis of defined cell types depending on their spatial location in the SVZ and identify HOPX as a marker of a subpopulation primed toward astrocytic fates...
September 11, 2018: Stem Cell Reports
Zihao Sun, Minzhe Zhu, Pin Lv, Lu Cheng, Qianfeng Wang, Pengxiang Tian, Zixiang Yan, Bo Wen
The naive embryonic stem cells (nESCs) display unique characteristics compared with the primed counterparts, but the underlying molecular mechanisms remain elusive. Here we investigate the functional roles of Lncenc1, a highly abundant long noncoding RNA in nESCs. Knockdown or knockout of Lncenc1 in mouse nESCs leads to a significantly decreased expression of core pluripotency genes and a significant reduction of colony formation capability. Furthermore, upon the depletion of Lncenc1, the expression of glycolysis-associated genes is significantly reduced, and the glycolytic activity is substantially impaired, as indicated by a more than 50% reduction in levels of glucose consumption, lactate production, and extracellular acidification rate...
September 11, 2018: Stem Cell Reports
Chad R Frasier, Helen Zhang, James Offord, Louis T Dang, David S Auerbach, Huilin Shi, Chunling Chen, Alica M Goldman, L Lee Eckhardt, Vassilios J Bezzerides, Jack M Parent, Lori L Isom
Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy with a high incidence of sudden unexpected death in epilepsy (SUDEP). Most DS patients carry de novo variants in SCN1A, resulting in Nav 1.1 haploinsufficiency. Because SCN1A is expressed in heart and in brain, we proposed that cardiac arrhythmia contributes to SUDEP in DS. We generated DS patient and control induced pluripotent stem cell-derived cardiac myocytes (iPSC-CMs). We observed increased sodium current (INa ) and spontaneous contraction rates in DS patient iPSC-CMs versus controls...
September 11, 2018: Stem Cell Reports
Daniel Gyllborg, Maqsood Ahmed, Enrique M Toledo, Spyridon Theofilopoulos, Shanzheng Yang, Charles Ffrench-Constant, Ernest Arenas
The development of midbrain dopaminergic (mDA) neurons is controlled by multiple morphogens and transcription factors. However, little is known about the role of extracellular matrix proteins in this process. Here we examined the function of roof plate-specific spondins (RSPO1-4) and the floor plate-specific, spondin 1 (SPON1). Only RSPO2 and SPON1 were expressed at high levels during mDA neurogenesis, and the receptor LGR5 was expressed by midbrain floor plate progenitors. Surprisingly, RSPO2, but not SPON1, specifically promoted the differentiation of mDA neuroblasts into mDA neurons in mouse primary cultures and embryonic stem cells (ESCs)...
September 11, 2018: Stem Cell Reports
Matthew S Elitt, H Elizabeth Shick, Mayur Madhavan, Kevin C Allan, Benjamin L L Clayton, Chen Weng, Tyler E Miller, Daniel C Factor, Lilianne Barbar, Baraa S Nawash, Zachary S Nevin, Angela M Lager, Yan Li, Fulai Jin, Drew J Adams, Paul J Tesar
Pelizaeus-Merzbacher disease (PMD) is a fatal X-linked disorder caused by loss of myelinating oligodendrocytes and consequent hypomyelination. The underlying cellular and molecular dysfunctions are not fully defined, but therapeutic enhancement of oligodendrocyte survival could restore functional myelination in patients. Here we generated pure, scalable quantities of induced pluripotent stem cell-derived oligodendrocyte progenitor cells (OPCs) from a severe mouse model of PMD, Plp1jimpy . Temporal phenotypic and transcriptomic studies defined an early pathological window characterized by endoplasmic reticulum (ER) stress and cell death as OPCs exit their progenitor state...
September 11, 2018: Stem Cell Reports
Virginia Teijeiro, Dapeng Yang, Sonali Majumdar, Federico González, Robert W Rickert, Chunlong Xu, Richard Koche, Nipun Verma, Eric C Lai, Danwei Huangfu
MicroRNAs (miRNAs) are the effectors of a conserved gene-silencing system with broad roles in post-transcriptional regulation. Due to functional overlaps, assigning specific functions to individual miRNAs has been challenging. DICER1 cleaves pre-miRNA hairpins into mature miRNAs, and previously Dicer1 knockout mouse embryonic stem cells have been generated to study miRNA function in early mouse development. Here we report an essential requirement of DICER1 for the self-renewal of human embryonic stem cells (hESCs)...
September 11, 2018: Stem Cell Reports
Chen-Yuan Tseng, Yu-Han Su, Shun-Min Yang, Kun-Yang Lin, Chun-Ming Lai, Elham Rastegari, Oyundari Amartuvshin, Yueh Cho, Yu Cai, Hwei-Jan Hsu
In developing organisms, proper tuning of the number of stem cells within a niche is critical for the maintenance of adult tissues; however, the involved mechanisms remain largely unclear. Here, we demonstrate that Thickveins (Tkv), a type I bone morphogenetic protein (BMP) receptor, acts in the Drosophila developing ovarian soma through a Smad-independent pathway to shape the distribution of BMP signal within the niche, impacting germline stem cell (GSC) recruitment and maintenance. Somatic Tkv promotes Egfr signaling to silence transcription of Dally, which localizes BMP signals on the cell surface...
September 11, 2018: Stem Cell Reports
Hana Golan, Rachel Shukrun, Revital Caspi, Einav Vax, Naomi Pode-Shakked, Sanja Goldberg, Oren Pleniceanu, Dekel D Bar-Lev, Michal Mark-Danieli, Sara Pri-Chen, Jasmine Jacob-Hirsch, Itamar Kanter, Ariel Trink, Ginette Schiby, Ron Bilik, Tomer Kalisky, Orit Harari-Steinberg, Amos Toren, Benjamin Dekel
Cancer stem cell (CSC) identification relies on transplantation assays of cell subpopulations sorted from fresh tumor samples. Here, we attempt to bypass limitations of abundant tumor source and predetermined immune selection by in vivo propagating patient-derived xenografts (PDX) from human malignant rhabdoid tumor (MRT), a rare and lethal pediatric neoplasm, to an advanced state in which most cells behave as CSCs. Stemness is then probed by comparative transcriptomics of serial PDXs generating a gene signature of epithelial to mesenchymal transition, invasion/motility, metastasis, and self-renewal, pinpointing putative MRT CSC markers...
September 11, 2018: Stem Cell Reports
Jennifer Veevers, Elie N Farah, Mirko Corselli, Alec D Witty, Karina Palomares, Jason G Vidal, Nil Emre, Christian T Carson, Kunfu Ouyang, Canzhao Liu, Patrick van Vliet, Maggie Zhu, Jeffrey M Hegarty, Dekker C Deacon, Jonathan D Grinstein, Ralf J Dirschinger, Kelly A Frazer, Eric D Adler, Kirk U Knowlton, Neil C Chi, Jody C Martin, Ju Chen, Sylvia M Evans
To facilitate understanding of human cardiomyocyte (CM) subtype specification, and the study of ventricular CM biology in particular, we developed a broadly applicable strategy for enrichment of ventricular cardiomyocytes (VCMs) derived from human embryonic stem cells (hESCs). A bacterial artificial chromosome transgenic H9 hESC line in which GFP expression was driven by the human ventricular-specific myosin light chain 2 (MYL2) promoter was generated, and screened to identify cell-surface markers specific for MYL2-GFP-expressing VCMs...
September 11, 2018: Stem Cell Reports
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