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Stem Cell Reports

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https://www.readbyqxmd.com/read/28528702/detailed-characterization-of-mesenchymal-stem-stromal-cells-from-a-large-cohort-of-aml-patients-demonstrates-a-definitive-link-to-treatment-outcomes
#1
Rafael Diaz de la Guardia, Belen Lopez-Millan, Jessie R Lavoie, Clara Bueno, Julio Castaño, Maite Gómez-Casares, Susana Vives, Laura Palomo, Manel Juan, Julio Delgado, Maria L Blanco, Josep Nomdedeu, Alberto Chaparro, Jose Luis Fuster, Eduardo Anguita, Michael Rosu-Myles, Pablo Menéndez
Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are key components of the hematopoietic niche thought to have a direct role in leukemia pathogenesis. BM-MSCs from patients with acute myeloid leukemia (AML) have been poorly characterized due to disease heterogeneity. We report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR), intermediate-risk (IR), and high-risk (HR) subgroups. Stable MSC cultures were successfully established and characterized from 40 of 46 AML patients irrespective of the risk subgroup...
May 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28528701/expansion-and-purification-are-critical-for-the-therapeutic-application-of-pluripotent-stem-cell-derived-myogenic-progenitors
#2
Jaemin Kim, Alessandro Magli, Sunny S K Chan, Vanessa K P Oliveira, Jianbo Wu, Radbod Darabi, Michael Kyba, Rita C R Perlingeiro
Recent reports have documented the differentiation of human pluripotent stem cells toward the skeletal myogenic lineage using transgene- and cell purification-free approaches. Although these protocols generate myocytes, they have not demonstrated scalability, safety, and in vivo engraftment, which are key aspects for their future clinical application. Here we recapitulate one prominent protocol, and show that it gives rise to a heterogeneous cell population containing myocytes and other cell types. Upon transplantation, the majority of human donor cells could not contribute to myofiber formation...
May 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28528700/directed-differentiation-of-human-pluripotent-stem-cells-to-microglia
#3
Panagiotis Douvaras, Bruce Sun, Minghui Wang, Ilya Kruglikov, Gregory Lallos, Matthew Zimmer, Cecile Terrenoire, Bin Zhang, Sam Gandy, Eric Schadt, Donald O Freytes, Scott Noggle, Valentina Fossati
Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the CNS, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microglia from pluripotent stem cells. Myeloid progenitors expressing CD14/CX3CR1 were generated within 30 days of differentiation from both embryonic and induced pluripotent stem cells (iPSCs). Further differentiation of the progenitors resulted in ramified microglia with highly motile processes, expressing typical microglial markers...
May 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28528699/steps-toward-maturation-of-embryonic-stem-cell-derived-cardiomyocytes-by-defined-physical-signals
#4
Nian Shen, Anne Knopf, Claas Westendorf, Udo Kraushaar, Julia Riedl, Hannah Bauer, Simone Pöschel, Shannon Lee Layland, Monika Holeiter, Stefan Knolle, Eva Brauchle, Ali Nsair, Svenja Hinderer, Katja Schenke-Layland
Cardiovascular disease remains a leading cause of mortality and morbidity worldwide. Embryonic stem cell-derived cardiomyocytes (ESC-CMs) may offer significant advances in creating in vitro cardiac tissues for disease modeling, drug testing, and elucidating developmental processes; however, the induction of ESCs to a more adult-like CM phenotype remains challenging. In this study, we developed a bioreactor system to employ pulsatile flow (1.48 mL/min), cyclic strain (5%), and extended culture time to improve the maturation of murine and human ESC-CMs...
May 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28528698/microrna-signatures-and-molecular-subtypes-of-glioblastoma-the-role-of-extracellular-transfer
#5
Jakub Godlewski, Ruben Ferrer-Luna, Arun K Rooj, Marco Mineo, Franz Ricklefs, Yuji S Takeda, M Oskar Nowicki, Elżbieta Salińska, Ichiro Nakano, Hakho Lee, Ralph Weissleder, Rameen Beroukhim, E Antonio Chiocca, Agnieszka Bronisz
Despite the importance of molecular subtype classification of glioblastoma (GBM), the extent of extracellular vesicle (EV)-driven molecular and phenotypic reprogramming remains poorly understood. To reveal complex subpopulation dynamics within the heterogeneous intratumoral ecosystem, we characterized microRNA expression and secretion in phenotypically diverse subpopulations of patient-derived GBM stem-like cells (GSCs). As EVs and microRNAs convey information that rearranges the molecular landscape in a cell type-specific manner, we argue that intratumoral exchange of microRNA augments the heterogeneity of GSC that is reflected in highly heterogeneous profile of microRNA expression in GBM subtypes...
May 17, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28528697/an-embryonic-stem-cell-specific-nurd-complex-functions-through-interaction-with-wdr5
#6
Ly-Sha Ee, Kurtis N McCannell, Yang Tang, Nancy Fernandes, W Rod Hardy, Michael R Green, Feixia Chu, Thomas G Fazzio
The Nucleosome Remodeling and Deacetylase (NuRD) complex is a chromatin regulatory complex that functions as a transcriptional co-repressor in metazoans. The NuRD subunit MBD3 is essential for targeting and assembly of a functional NuRD complex as well as embryonic stem cell (ESC) pluripotency. Three MBD3 isoforms (MBD3A, MBD3B, and MBD3C) are expressed in mouse. Here, we find that the MBD3C isoform contains a unique 50-amino-acid N-terminal region that is necessary for MBD3C to specifically interact with the histone H3 binding protein WDR5...
May 17, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28528696/reprogramming-of-dermal-fibroblasts-into-osteo-chondrogenic-cells-with-elevated-osteogenic-potency-by-defined-transcription-factors
#7
Yinxiang Wang, Ming-Hoi Wu, May Pui Lai Cheung, Mai Har Sham, Haruhiko Akiyama, Danny Chan, Kathryn S E Cheah, Martin Cheung
Recent studies using defined transcription factors to convert skin fibroblasts into chondrocytes have raised the question of whether osteo-chondroprogenitors expressing SOX9 and RUNX2 could also be generated during the course of the reprogramming process. Here, we demonstrated that doxycycline-inducible expression of reprogramming factors (KLF4 [K] and c-MYC [M]) for 6 days were sufficient to convert murine fibroblasts into SOX9(+)/RUNX2(+) cellular aggregates and together with SOX9 (S) promoted the conversion efficiency when cultured in a defined stem cell medium, mTeSR...
May 15, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28506534/neurod1-instructs-neuronal-conversion-in-non-reactive-astrocytes
#8
Rebecca Brulet, Taito Matsuda, Ling Zhang, Carlos Miranda, Mauro Giacca, Brian K Kaspar, Kinichi Nakashima, Jenny Hsieh
Currently, all methods for converting non-neuronal cells into neurons involve injury to the brain; however, whether neuronal transdifferentiation can occur long after the period of insult remains largely unknown. Here, we use the transcription factor NEUROD1, previously shown to convert reactive glial cells to neurons in the cortex, to determine whether astrocyte-to-neuron transdifferentiation can occur under physiological conditions. We utilized adeno-associated virus 9 (AAV9), which crosses the blood-brain barrier without injury, to deliver NEUROD1 to astrocytes through an intravascular route...
May 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28506533/schwann-cell-precursors-from-human-pluripotent-stem-cells-as-a-potential-therapeutic-target-for-myelin-repair
#9
Han-Seop Kim, Jungwoon Lee, Da Yong Lee, Young-Dae Kim, Jae Yun Kim, Hyung Jin Lim, Sungmin Lim, Yee Sook Cho
Schwann cells play a crucial role in successful nerve repair and regeneration by supporting both axonal growth and myelination. However, the sources of human Schwann cells are limited both for studies of Schwann cell development and biology and for the development of treatments for Schwann cell-associated diseases. Here, we provide a rapid and scalable method to produce self-renewing Schwann cell precursors (SCPs) from human pluripotent stem cells (hPSCs), using combined sequential treatment with inhibitors of the TGF-β and GSK-3 signaling pathways, and with neuregulin-1 for 18 days under chemically defined conditions...
May 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28506532/accreditation-of-biosafe-clinical-grade-human-embryonic-stem-cells-according-to-chinese-regulations
#10
Qi Gu, Juan Wang, Lei Wang, Zheng-Xin Liu, Wan-Wan Zhu, Yuan-Qing Tan, Wei-Fang Han, Jun Wu, Chun-Jing Feng, Jin-Hui Fang, Lei Liu, Liu Wang, Wei Li, Xiao-Yang Zhao, Bao-Yang Hu, Jie Hao, Qi Zhou
Human embryonic stem cells (hESCs) are promising in regenerative medicine. Although several hESC-based clinical trials are under way, a widely accepted standard of clinical-grade cells remains obscure. To attain a completely xeno-free clinical-grade cell line, the system must be free of xenogenic components, the cells must have a comprehensive set of functions, and good manufacturing practice conditions must be used. In this study, following these criteria, we successfully derived two hESC lines, which were thereby considered "clinical-grade embryonic stem cells"...
May 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28506535/sca-1-expression-level-identifies-quiescent-hematopoietic-stem-and-progenitor-cells
#11
Mina N F Morcos, Kristina B Schoedel, Anja Hoppe, Rayk Behrendt, Onur Basak, Hans C Clevers, Axel Roers, Alexander Gerbaulet
Blood cell generation depends on continuous cellular output by the sequential hierarchy of hematopoietic stem cell (HSC) and progenitor populations that all contain quiescent and actively cycling cells. Hematopoietic stem and progenitor cells (HSPCs) express the surface molecule Stem cell antigen 1 (SCA-1/LY6A). Using histone 2B-red fluorescent fusion protein label retention and cell-cycle reporter mice, we demonstrate that high SCA-1 expression (SCA-1(hi)) identifies not only quiescent HSCs but quiescent cells on all hierarchical levels within the lineage(-)SCA-1(+)KIT(+) (LSK) population...
May 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28479306/intestinal-stem-cell-pool-regulation-in-drosophila
#12
Yinhua Jin, Parthive H Patel, Alexander Kohlmaier, Bojana Pavlovic, Chenge Zhang, Bruce A Edgar
Intestinal epithelial renewal is mediated by intestinal stem cells (ISCs) that exist in a state of neutral drift, wherein individual ISC lineages are regularly lost and born but ISC numbers remain constant. To test whether an active mechanism maintains stem cell pools in the Drosophila midgut, we performed partial ISC depletion. In contrast to the mouse intestine, Drosophila ISCs failed to repopulate the gut after partial depletion. Even when the midgut was challenged to regenerate by infection, ISCs retained normal proportions of asymmetric division and ISC pools did not increase...
May 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28479305/increasing-human-neural-stem-cell-transplantation-dose-alters-oligodendroglial-and-neuronal-differentiation-after-spinal-cord-injury
#13
Katja M Piltti, Gabriella M Funes, Sabrina N Avakian, Ara A Salibian, Kevin I Huang, Krystal Carta, Noriko Kamei, Lisa A Flanagan, Edwin S Monuki, Nobuko Uchida, Brian J Cummings, Aileen J Anderson
Multipotent human central nervous system-derived neural stem cells transplanted at doses ranging from 10,000 (low) to 500,000 (very high) cells differentiated predominantly into the oligodendroglial lineage. However, while the number of engrafted cells increased linearly in relationship to increasing dose, the proportion of oligodendrocytic cells declined. Increasing dose resulted in a plateau of engraftment, enhanced neuronal differentiation, and increased distal migration caudal to the transplantation sites...
May 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28479304/understanding-hematopoietic-stem-cell-development-through-functional-correlation-of-their-proliferative-status-with-the-intra-aortic-cluster-architecture
#14
Antoniana Batsivari, Stanislav Rybtsov, Celine Souilhol, Anahi Binagui-Casas, David Hills, Suling Zhao, Paul Travers, Alexander Medvinsky
During development, hematopoietic stem cells (HSCs) emerge in the aorta-gonad-mesonephros (AGM) region through a process of multi-step maturation and expansion. While proliferation of adult HSCs is implicated in the balance between self-renewal and differentiation, very little is known about the proliferation status of nascent HSCs in the AGM region. Using Fucci reporter mice that enable in vivo visualization of cell-cycle status, we detect increased proliferation during pre-HSC expansion followed by a slowing down of cycling once cells start to acquire a definitive HSC state, similar to fetal liver HSCs...
May 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28479303/a-common-origin-for-b-1a-and-b-2-lymphocytes-in-clonal-pre-hematopoietic-stem-cells
#15
Brandon K Hadland, Barbara Varnum-Finney, Pankaj K Mandal, Derrick J Rossi, Michael G Poulos, Jason M Butler, Shahin Rafii, Mervin C Yoder, Momoko Yoshimoto, Irwin D Bernstein
Recent evidence points to the embryonic emergence of some tissue-resident innate immune cells, such as B-1a lymphocytes, prior to and independently of hematopoietic stem cells (HSCs). However, whether the full hematopoietic repertoire of embryonic HSCs initially includes these unique lineages of innate immune cells has been difficult to assess due to lack of clonal assays that identify and assess HSC precursor (pre-HSC) potential. Here, by combining index sorting of single embryonic hemogenic precursors with in vitro HSC maturation and transplantation assays, we analyze emerging pre-HSCs at the single-cell level, revealing their unique stage-specific properties and clonal lineage potential...
May 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28479302/comprehensive-monosynaptic-rabies-virus-mapping-of-host-connectivity-with-neural-progenitor-grafts-after-spinal-cord-injury
#16
Andrew F Adler, Corinne Lee-Kubli, Hiromi Kumamaru, Ken Kadoya, Mark H Tuszynski
Neural progenitor cells grafted to sites of spinal cord injury have supported electrophysiological and functional recovery in several studies. Mechanisms associated with graft-related improvements in outcome appear dependent on functional synaptic integration of graft and host systems, although the extent and diversity of synaptic integration of grafts with hosts are unknown. Using transgenic mouse spinal neural progenitor cell grafts expressing the TVA and G-protein components of the modified rabies virus system, we initiated monosynaptic tracing strictly from graft neurons placed in sites of cervical spinal cord injury...
May 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28479301/bone-size-and-quality-regulation-concerted-actions-of-mtor-in-mesenchymal-stromal-cells-and-osteoclasts
#17
Hongguang Wu, Zhixiang Wu, Ping Li, Qian Cong, Rongrong Chen, Wenrui Xu, Soma Biswas, Huijuan Liu, Xuechun Xia, Shanshan Li, Weiwei Hu, Zhenlin Zhang, Samy L Habib, Lingli Zhang, Jun Zou, Hongbing Zhang, Weihong Zhang, Baojie Li
The bone size and quality, acquired during adolescent growth under the influence of anabolic hormones, growth factors, and nutrients, determine the height and bone stability and forecast osteoporosis risks in late life. Yet bone size and quality control mechanisms remain enigmatic. To study the roles of mammalian target of rapamycin (mTOR) signaling, sensor of growth factors and nutrients, in bone size and quality regulation, we ablated Tsc1, a suppressor of mTOR, in mesenchymal stromal cells (MSCs), monocytes, or their progenies osteoblasts and osteoclasts...
April 29, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28416285/atypical-pkc-and-notch-inhibition-differentially-modulate-cortical-interneuron-subclass-fate-from-embryonic-stem-cells
#18
David J Tischfield, Junho Kim, Stewart A Anderson
Recent studies indicate that the location of neurogenesis within the medial ganglionic eminence (MGE) critically influences the fate determination of cortical interneuron subgroups, with parvalbumin (Pv) interneurons originating from subventricular zone divisions and somatostatin (Sst) interneurons primarily arising from apical divisions. The aPKC-CBP and Notch signaling pathways regulate the transition from apical to basal progenitor and their differentiation into post-mitotic neurons. We find that aPKC inhibition enhances intermediate neurogenesis from stem cell-derived MGE progenitors, resulting in a markedly increased ratio of Pv- to Sst-expressing interneurons...
April 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28392217/high-throughput-and-cost-effective-characterization-of-induced-pluripotent-stem-cells
#19
Matteo D'Antonio, Grace Woodruff, Jason L Nathanson, Agnieszka D'Antonio-Chronowska, Angelo Arias, Hiroko Matsui, Roy Williams, Cheryl Herrera, Sol M Reyna, Gene W Yeo, Lawrence S B Goldstein, Athanasia D Panopoulos, Kelly A Frazer
Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) offers the possibility of studying the molecular mechanisms underlying human diseases in cell types difficult to extract from living patients, such as neurons and cardiomyocytes. To date, studies have been published that use small panels of iPSC-derived cell lines to study monogenic diseases. However, to study complex diseases, where the genetic variation underlying the disorder is unknown, a sizable number of patient-specific iPSC lines and controls need to be generated...
April 4, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28392216/ipscore-a-resource-of-222-ipsc-lines-enabling-functional-characterization-of-genetic-variation-across-a-variety-of-cell-types
#20
Athanasia D Panopoulos, Matteo D'Antonio, Paola Benaglio, Roy Williams, Sherin I Hashem, Bernhard M Schuldt, Christopher DeBoever, Angelo D Arias, Melvin Garcia, Bradley C Nelson, Olivier Harismendy, David A Jakubosky, Margaret K R Donovan, William W Greenwald, KathyJean Farnam, Megan Cook, Victor Borja, Carl A Miller, Jonathan D Grinstein, Frauke Drees, Jonathan Okubo, Kenneth E Diffenderfer, Yuriko Hishida, Veronica Modesto, Carl T Dargitz, Rachel Feiring, Chang Zhao, Aitor Aguirre, Thomas J McGarry, Hiroko Matsui, He Li, Joaquin Reyna, Fangwen Rao, Daniel T O'Connor, Gene W Yeo, Sylvia M Evans, Neil C Chi, Kristen Jepsen, Naoki Nariai, Franz-Josef Müller, Lawrence S B Goldstein, Juan Carlos Izpisua Belmonte, Eric Adler, Jeanne F Loring, W Travis Berggren, Agnieszka D'Antonio-Chronowska, Erin N Smith, Kelly A Frazer
Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection of systematically derived and characterized iPSC lines from 222 ethnically diverse individuals that allows for both familial and association-based genetic studies. iPSCORE lines are pluripotent with high genomic integrity (no or low numbers of somatic copy-number variants) as determined using high-throughput RNA-sequencing and genotyping arrays, respectively...
April 3, 2017: Stem Cell Reports
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