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Stem Cell Reports

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https://www.readbyqxmd.com/read/29153988/isolation-and-comparative-transcriptome-analysis-of-human-fetal-and-ipsc-derived-cone-photoreceptor-cells
#1
Emily Welby, Jorn Lakowski, Valentina Di Foggia, Dimitri Budinger, Anai Gonzalez-Cordero, Aaron T L Lun, Michael Epstein, Aara Patel, Elisa Cuevas, Kamil Kruczek, Arifa Naeem, Federico Minneci, Mike Hubank, David T Jones, John C Marioni, Robin R Ali, Jane C Sowden
Loss of cone photoreceptors, crucial for daylight vision, has the greatest impact on sight in retinal degeneration. Transplantation of stem cell-derived L/M-opsin cones, which form 90% of the human cone population, could provide a feasible therapy to restore vision. However, transcriptomic similarities between fetal and stem cell-derived cones remain to be defined, in addition to development of cone cell purification strategies. Here, we report an analysis of the human L/M-opsin cone photoreceptor transcriptome using an AAV2/9...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29153990/cell-type-dependent-alzheimer-s-disease-phenotypes-probing-the-biology-of%C3%A2-selective-neuronal-vulnerability
#2
Christina R Muratore, Constance Zhou, Meichen Liao, Marty A Fernandez, Walter M Taylor, Valentina N Lagomarsino, Richard V Pearse, Heather C Rice, Joseph M Negri, Amy He, Priya Srikanth, Dana G Callahan, Taehwan Shin, Monica Zhou, David A Bennett, Scott Noggle, J Christopher Love, Dennis J Selkoe, Tracy L Young-Pearse
Alzheimer's disease (AD) induces memory and cognitive impairment in the absence of motor and sensory deficits during its early and middle course. A major unresolved question is the basis for this selective neuronal vulnerability. Aβ, which plays a central role in AD pathogenesis, is generated throughout the brain, yet some regions outside of the limbic and cerebral cortices are relatively spared from Aβ plaque deposition and synapse loss. Here, we examine neurons derived from iPSCs of patients harboring an amyloid precursor protein mutation to quantify AD-relevant phenotypes following directed differentiation to rostral fates of the brain (vulnerable) and caudal fates (relatively spared) in AD...
November 13, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29153989/psen1-mutant-ipsc-derived-model-reveals-severe-astrocyte-pathology-in-alzheimer-s-disease
#3
Minna Oksanen, Andrew J Petersen, Nikolay Naumenko, Katja Puttonen, Šárka Lehtonen, Max Gubert Olivé, Anastasia Shakirzyanova, Stina Leskelä, Timo Sarajärvi, Matti Viitanen, Juha O Rinne, Mikko Hiltunen, Annakaisa Haapasalo, Rashid Giniatullin, Pasi Tavi, Su-Chun Zhang, Katja M Kanninen, Riikka H Hämäläinen, Jari Koistinaho
Alzheimer's disease (AD) is a common neurodegenerative disorder and the leading cause of cognitive impairment. Due to insufficient understanding of the disease mechanisms, there are no efficient therapies for AD. Most studies have focused on neuronal cells, but astrocytes have also been suggested to contribute to AD pathology. We describe here the generation of functional astrocytes from induced pluripotent stem cells (iPSCs) derived from AD patients with PSEN1 ΔE9 mutation, as well as healthy and gene-corrected isogenic controls...
November 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29153991/serine-347-phosphorylation-by-jnks-negatively-regulates-oct4-protein-stability-in-mouse-embryonic-stem-cells
#4
Ki Beom Bae, Dong Hoon Yu, Kun Yeong Lee, Ke Yao, Joohyun Ryu, Do Young Lim, Tatyana A Zykova, Myoung Ok Kim, Ann M Bode, Zigang Dong
The POU transcription factor OCT4 is critical for maintaining the undifferentiated state of embryonic stem cells (ESCs) and generating induced pluripotent stem cells (iPSCs), but its precise mechanisms of action remain poorly understood. Here, we investigated the role of OCT4 phosphorylation in the biological functions of ESCs. We observed that c-Jun N-terminal kinases (JNKs) directly interacted with and phosphorylated OCT4 at serine 347, which inhibited the transcriptional activity of OCT4. Moreover, phosphorylation of OCT4 induced binding of FBXW8, which reduced OCT4 protein stability and enhanced its proteasomal degradation...
November 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29129683/non-monotonic-changes-in-progenitor-cell-behavior-and-gene-expression-during-aging-of-the-adult-v-svz-neural-stem-cell-niche
#5
Maria Apostolopoulou, Thomas R Kiehl, Mark Winter, Edgar Cardenas De La Hoz, Nathan C Boles, Christopher S Bjornsson, Kristen L Zuloaga, Susan K Goderie, Yue Wang, Andrew R Cohen, Sally Temple
Neural stem cell activity in the ventricular-subventricular zone (V-SVZ) decreases with aging, thought to occur by a unidirectional decline. However, by analyzing the V-SVZ transcriptome of male mice at 2, 6, 18, and 22 months, we found that most of the genes that change significantly over time show a reversal of trend, with a maximum or minimum expression at 18 months. In vivo, MASH1(+) progenitor cells decreased in number and proliferation between 2 and 18 months but increased between 18 and 22 months...
November 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29153987/development-and-characterization-of-a-human-and-mouse-intestinal-epithelial-cell-monolayer-platform
#6
Kenji Kozuka, Ying He, Samantha Koo-McCoy, Padmapriya Kumaraswamy, Baoming Nie, Karen Shaw, Priscilla Chan, Michael Leadbetter, Limin He, Jason G Lewis, Ziyang Zhong, Dominique Charmot, Marwan Balaa, Andrew J King, Jeremy S Caldwell, Matthew Siegel
We describe the development and characterization of a mouse and human epithelial cell monolayer platform of the small and large intestines, with a broad range of potential applications including the discovery and development of minimally systemic drug candidates. Culture conditions for each intestinal segment were optimized by correlating monolayer global gene expression with the corresponding tissue segment. The monolayers polarized, formed tight junctions, and contained a diversity of intestinal epithelial cell lineages...
November 7, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29153986/efficient-induction-of-syncytiotrophoblast-layer-ii-cells-from-trophoblast-stem-cells-by-canonical-wnt-signaling-activation
#7
Dongmei Zhu, Xia Gong, Liyun Miao, Junshun Fang, Jian Zhang
The syncytiotrophoblast layer is the most critical and prominent tissue in placenta. SynT cells are differentiated from trophoblast stem cells (TSCs) during early embryogenesis. Mouse TSCs can spontaneously differentiate into cells of mixed lineages in vitro upon withdrawal of stemness-maintaining factors. However, differentiation into defined placental cell lineages remains challenging. We report here that canonical Wnt signaling activation robustly induces expression of SynT-II lineage-specific genes Gcm1 and SynB and suppresses markers of other placental lineages...
November 7, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29129685/small-rna-sequencing-reveals-dlk1-dio3-locus-embedded-micrornas-as-major-drivers-of-ground-state-pluripotency
#8
Sharif Moradi, Ali Sharifi-Zarchi, Amirhossein Ahmadi, Sepideh Mollamohammadi, Alexander Stubenvoll, Stefan Günther, Ghasem Hosseini Salekdeh, Sassan Asgari, Thomas Braun, Hossein Baharvand
Ground-state pluripotency is a cell state in which pluripotency is established and maintained through efficient repression of endogenous differentiation pathways. Self-renewal and pluripotency of embryonic stem cells (ESCs) are influenced by ESC-associated microRNAs (miRNAs). Here, we provide a comprehensive assessment of the "miRNome" of ESCs cultured under conditions favoring ground-state pluripotency. We found that ground-state ESCs express a distinct set of miRNAs compared with ESCs grown in serum. Interestingly, most "ground-state miRNAs" are encoded by an imprinted region on chromosome 12 within the Dlk1-Dio3 locus...
November 7, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29129684/rhoa-gtpase-controls-yap-mediated-ereg-signaling-in-small-intestinal-stem-cell-maintenance
#9
Ming Liu, Zheng Zhang, Leesa Sampson, Xuan Zhou, Kodandaramireddy Nalapareddy, Yuxin Feng, Shailaja Akunuru, Jaime Melendez, Ashley Kuenzi Davis, Feng Bi, Hartmut Geiger, Mei Xin, Yi Zheng
RHOA, a founding member of the Rho GTPase family, is critical for actomyosin dynamics, polarity, and morphogenesis in response to developmental cues, mechanical stress, and inflammation. In murine small intestinal epithelium, inducible RHOA deletion causes a loss of epithelial polarity, with disrupted villi and crypt organization. In the intestinal crypts, RHOA deficiency results in reduced cell proliferation, increased apoptosis, and a loss of intestinal stem cells (ISCs) that mimic effects of radiation damage...
November 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29129686/naive-like-esrrb-ipscs-with-the-capacity-for-rapid-neural-differentiation
#10
Fumihiko Kisa, Seiji Shiozawa, Keisuke Oda, Sho Yoshimatsu, Mari Nakamura, Ikuko Koya, Kenji Kawai, Sadafumi Suzuki, Hideyuki Okano
Several groups have reported the existence of a form of pluripotency that resembles that of mouse embryonic stem cells (mESCs), i.e., a naive state, in human pluripotent stem cells; however, the characteristics vary between reports. The nuclear receptor ESRRB is expressed in mESCs and plays a significant role in their self-renewal, but its expression has not been observed in most naive-like human induced pluripotent stem cells (hiPSCs). In this study, we modified several methods for converting hiPSCs into a naive state through the transgenic expression of several reprogramming factors...
November 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29129682/spatial-and-sex-dependent-responses-of-adult-endogenous-neural-stem-cells-to-alcohol-consumption
#11
Erica L McGrath, Junling Gao, Yong-Fang Kuo, Tiffany J Dunn, Moniqua J Ray, Kelly T Dineley, Kathryn A Cunningham, Bhupendra S Kaphalia, Ping Wu
Chronic alcohol abuse results in alcohol-related neurodegeneration, and critical gaps in our knowledge hinder therapeutic development. Neural stem cells (NSCs) are a subpopulation of cells within the adult brain that contribute to brain maintenance and recovery. While it is known that alcohol alters NSCs, little is known about how NSC response to alcohol is related to sex, brain region, and stage of differentiation. Understanding these relationships will aid in therapeutic development. Here, we used an inducible transgenic mouse model to track the stages of differentiation of adult endogenous NSCs and observed distinct NSC behaviors in three brain regions (subventricular zone, subgranular zone, and tanycyte layer) after long-term alcohol consumption...
November 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29129681/decreased-sirtuin-deacetylase-activity-in-lrrk2-g2019s-ipsc-derived-dopaminergic-neurons
#12
Andrew J Schwab, Samantha L Sison, Michael R Meade, Katarzyna A Broniowska, John A Corbett, Allison D Ebert
Mitochondrial changes have long been implicated in the pathogenesis of Parkinson's disease (PD). The glycine to serine mutation (G2019S) in leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause for PD and has been shown to impair mitochondrial function and morphology in multiple model systems. We analyzed mitochondrial function in LRRK2 G2019S induced pluripotent stem cell (iPSC)-derived neurons to determine whether the G2019S mutation elicits similar mitochondrial deficits among central and peripheral nervous system neuron subtypes...
October 31, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29141234/elevated-p53-activities-restrict-differentiation-potential-of-microrna-deficient-pluripotent-stem-cells
#13
Zhong Liu, Cheng Zhang, Maria Skamagki, Alireza Khodadadi-Jamayran, Wei Zhang, Dexin Kong, Chia-Wei Chang, Jingyang Feng, Xiaosi Han, Tim M Townes, Hu Li, Kitai Kim, Rui Zhao
Pluripotent stem cells (PSCs) deficient for microRNAs (miRNAs), such as Dgcr8(-/-) or Dicer(-/-) embryonic stem cells (ESCs), contain no mature miRNA and cannot differentiate into somatic cells. How miRNA deficiency causes differentiation defects remains poorly understood. Here, we report that miR-302 is sufficient to enable neural differentiation of differentiation-incompetent Dgcr8(-/-) ESCs. Our data showed that miR-302 directly suppresses the tumor suppressor p53, which is modestly upregulated in Dgcr8(-/-) ESCs and serves as a barrier restricting neural differentiation...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29141233/mirnome-profiling-of-purified-endoderm-and-mesoderm-differentiated-from-hescs-reveals-functions-of-mir-483-3p-and-mir-1263-for-cell-fate-decisions
#14
Daichi Ishikawa, Ulf Diekmann, Jan Fiedler, Annette Just, Thomas Thum, Sigurd Lenzen, Ortwin Naujok
Pluripotent stem cells hold great promise for regenerative medicine since they can differentiate into all somatic cells. MicroRNAs (miRNAs) could be important for the regulation of these cell-fate decisions. Profiling of miRNAs revealed 19 differentially expressed miRNAs in the endoderm and 29 in the mesoderm when analyzing FACS-purified cells derived from human embryonic stem cells. The mesodermal-enriched miR-483-3p was identified as an important regulator for the generation of mesodermal PDGFRA(+) paraxial cells...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29141232/foxp1-promotes-embryonic-neural-stem-cell-differentiation-by-repressing-jagged1-expression
#15
Luca Braccioli, Stephin J Vervoort, Youri Adolfs, Cobi J Heijnen, Onur Basak, R Jeroen Pasterkamp, Cora H Nijboer, Paul J Coffer
Mutations in FOXP1 have been linked to neurodevelopmental disorders including intellectual disability and autism; however, the underlying molecular mechanisms remain ill-defined. Here, we demonstrate with RNA and chromatin immunoprecipitation sequencing that FOXP1 directly regulates genes controlling neurogenesis. We show that FOXP1 is expressed in embryonic neural stem cells (NSCs), and modulation of FOXP1 expression affects both neuron and astrocyte differentiation. Using a murine model of cortical development, FOXP1-knockdown in utero was found to reduce NSC differentiation and migration during corticogenesis...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29107597/naked-mole-rat-cells-have-a-stable-epigenome-that-resists-ipsc%C3%A2-reprogramming
#16
Li Tan, Zhonghe Ke, Gregory Tombline, Nicholas Macoretta, Kevin Hayes, Xiao Tian, Ruitu Lv, Julia Ablaeva, Michael Gilbert, Natarajan V Bhanu, Zuo-Fei Yuan, Benjamin A Garcia, Yujiang G Shi, Yang Shi, Andrei Seluanov, Vera Gorbunova
Naked mole rat (NMR) is a valuable model for aging and cancer research due to its exceptional longevity and cancer resistance. We observed that the reprogramming efficiency of NMR fibroblasts in response to OSKM was drastically lower than that of mouse fibroblasts. Expression of SV40 LargeT antigen (LT) dramatically improved reprogramming of NMR fibroblasts. Inactivation of Rb alone, but not p53, was sufficient to improve reprogramming efficiency, suggesting that NMR chromatin may be refractory to reprogramming...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29107596/default-patterning-produces-pan-cortical-glutamatergic-and-cge-lge-like-gabaergic-neurons-from-human-pluripotent-stem-cells
#17
Crina M Floruta, Ruofei Du, Huining Kang, Jason L Stein, Jason P Weick
Default differentiation of human pluripotent stem cells has been promoted as a model of cortical development. In this study, a developmental transcriptome analysis of default-differentiated hPSNs revealed a gene expression program resembling in vivo CGE/LGE subpallial domains and GABAergic signaling. A combination of bioinformatic, functional, and immunocytochemical analysis further revealed that hPSNs consist of both cortical glutamatergic and CGE-like GABAergic neurons. This study provides a comprehensive characterization of the heterogeneous group of neurons produced by default differentiation and insight into future directed differentiation strategies...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29107595/activation-of-the-aryl-hydrocarbon-receptor-interferes-with-early-embryonic-development
#18
Manolis Gialitakis, Mauro Tolaini, Ying Li, Mercedes Pardo, Lu Yu, Ana Toribio, Jyoti S Choudhary, Kathy Niakan, Venizelos Papayannopoulos, Brigitta Stockinger
The transcriptional program of early embryonic development is tightly regulated by a set of well-defined transcription factors that suppress premature expression of differentiation genes and sustain the pluripotent identity. It is generally accepted that this program can be perturbed by environmental factors such as chemical pollutants; however, the precise molecular mechanisms remain unknown. The aryl hydrocarbon receptor (AHR) is a widely expressed nuclear receptor that senses environmental stimuli and modulates target gene expression...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29107594/genes-associated-with-pancreas-development-and-function-maintain-open-chromatin-in-ipscs-generated-from-human-pancreatic-beta-cells
#19
Matthias Thurner, Liraz Shenhav, Agata Wesolowska-Andersen, Amanda J Bennett, Amy Barrett, Anna L Gloyn, Mark I McCarthy, Nicola L Beer, Shimon Efrat
Current in vitro islet differentiation protocols suffer from heterogeneity and low efficiency. Induced pluripotent stem cells (iPSCs) derived from pancreatic beta cells (BiPSCs) preferentially differentiate toward endocrine pancreas-like cells versus those from fibroblasts (FiPSCs). We interrogated genome-wide open chromatin in BiPSCs and FiPSCs via ATAC-seq and identified ∼8.3k significant, differential open chromatin sites (DOCS) between the two iPSC subtypes (false discovery rate [FDR] < 0.05). DOCS where chromatin was more accessible in BiPSCs (Bi-DOCS) were significantly enriched for known regulators of endodermal development, including bivalent and weak enhancers, and FOXA2 binding sites (FDR < 0...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29107593/escape-from-pluripotency-via-inhibition-of-tgf-%C3%AE-bmp-and-activation-of-wnt-signaling-accelerates-differentiation-and-aging-in-hpsc-progeny-cells
#20
Koki Fujimori, Takuya Matsumoto, Fumihiko Kisa, Nobutaka Hattori, Hideyuki Okano, Wado Akamatsu
Human pluripotent stem cells (hPSCs) represent a potentially valuable cell source for applications in cell replacement therapy, drug development, and disease modeling. For all these uses, it is necessary to develop reproducible and robust protocols for differentiation into desired cell types. However, differentiation protocols remain unstable and inefficient, which makes minimizing the differentiation variance among hPSC lines and obtaining purified terminally differentiated cells extremely time consuming. Here, we report a simple treatment with three small molecules-SB431542, dorsomorphine, and CHIR99021-that enhanced hPSC differentiation into three germ layers with a chemically transitional embryoid-body-like state (CTraS)...
November 14, 2017: Stem Cell Reports
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