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Stem cell reports 27건

  1. [해외논문]   Ihor Lemischka (1953-2017)   SCIE

    Lansdorp, Peter
    Stem cell reports v.10 no.2 ,pp. 329 - 330 , 2018 ,

    초록

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

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  2. [해외논문]   BAK/BAX-Mediated Apoptosis Is a Myc -Induced Roadblock to Reprogramming   SCIE

    Kim, Esther J.Y. (The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia ) , Anko, Minna-Liisa (Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Development and Stem Cells Program, Monash University, Clayton, VIC 3800, Australia ) , Flensberg, Christoffer (The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia ) , Majewski, Ian J. (The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia ) , Geng, Fan-Suo (The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia ) , Firas, Jaber (Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Development and Stem Cells Program, Monash University, Clayton, VIC 3800, Australia ) , Huang, David C.S. (The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia ) , van Delft, Mark F. (The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia ) , Heath, Joan K. (The Walter and Eliza H)
    Stem cell reports v.10 no.2 ,pp. 331 - 338 , 2018 ,

    초록

    Summary Despite intensive efforts to optimize the process, reprogramming differentiated cells to induced pluripotent stem cells (iPSCs) remains inefficient. The most common combination of transcription factors employed comprises OCT4 , KLF4 , SOX2, and MYC (OKSM). If MYC is omitted (OKS), reprogramming efficiency is reduced further. Cells must overcome several obstacles to reach the pluripotent state, one of which is apoptosis. To directly determine how extensively apoptosis limits reprogramming, we exploited mouse embryonic fibroblasts (MEFs) lacking the two essential mediators of apoptosis, BAK and BAX. Our results show that reprogramming is enhanced in MEFs deficient in BAK and BAX, but only when MYC is part of the reprogramming cocktail. Thus, the propensity for Myc overexpression to elicit apoptosis creates a significant roadblock to reprogramming under OKSM conditions. Our results suggest that blocking apoptosis during reprogramming may enhance the derivation of iPSCs for research and therapeutic purposes. Highlights • We generated MEFS lacking two essential mediators of apoptosis, BAK and BAX • Loss of BAK and BAX significantly enhances MEF reprogramming in the presence of MYC • Thus, mitochondrial apoptosis limits reprogramming of MEFs in the presence of MYC • The integrity of the genome is not reduced in reprogrammed MEFs lacking BAK and BAX In this article, Heath, van Delft, and colleagues show that mitochondrial apoptosis limits OKSM-mediated reprogramming of MEFs. Not only is reprogramming of MEFs lacking the two essential mediators of mitochondrial apoptosis, BAK and BAX, significantly enhanced in the presence of MYC, but reprogramming in these conditions does not compromise genome integrity.

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  3. [해외논문]   Cell-Cycle-Specific Function of p53 in Fanconi Anemia Hematopoietic Stem and Progenitor Cell Proliferation   SCIE

    Li, Xiaoli (Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA ) , Wilson, Andrew F. (Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA ) , Du, Wei (Department of Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV 26506, USA ) , Pang, Qishen (Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA)
    Stem cell reports v.10 no.2 ,pp. 339 - 346 , 2018 ,

    초록

    Summary Overactive p53 has been proposed as an important pathophysiological factor for bone marrow failure syndromes, including Fanconi anemia (FA). Here, we report a p53-dependent effect on hematopoietic stem and progenitor cell (HSPC) proliferation in mice deficient for the FA gene Fanca . Deletion of p53 in Fanca −/− mice leads to replicative exhaustion of the hematopoietic stem cell (HSC) in transplant recipients. Using Fanca −/− HSCs expressing the separation-of-function mutant p53 515C transgene, which selectively impairs the p53 function in apoptosis but keeps its cell-cycle checkpoint activities intact, we show that the p53 cell-cycle function is specifically required for the regulation of Fanca −/− HSC proliferation. Our results demonstrate that p53 plays a compensatory role in preventing FA HSCs from replicative exhaustion and suggest a cautious approach to manipulating p53 signaling as a therapeutic utility in FA. Highlights • Loss of p53 in Fanca −/− mice leads to progressive decline of HSC reservoir • p53 deficiency leads to proliferative exhaustion of Fanca −/− HSCs • The cell-cycle function of p53 is required for preventing Fanca −/− HSC exhaustion In this article, Pang and colleagues demonstrate a p53-dependent HSPC proliferation regulation in mice deficient for the Fanca gene in the Fanconi anemia (FA) pathway. They show that the p53 cell-cycle function is specifically required for the regulation of FA HSC proliferation. These results suggest that overactive p53 may represent a compensatory checkpoint mechanism for FA HSC proliferation.

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  4. [해외논문]   Impact of Swiprosin-1/Efhd2 on Adult Hippocampal Neurogenesis   SCIE

    Regensburger, Martin (Department of Stem Cell Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Glueckstrasse 6, Erlangen 91054, Germany ) , Prots, Iryna (Department of Stem Cell Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Glueckstrasse 6, Erlangen 91054, Germany ) , Reimer, Dorothea (Department of Molecular Immunology, Department of Internal Medicine III, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Glueckstrasse 6, Erlangen 91054, Germany ) , Brachs, Sebastian (Department of Molecular Immunology, Department of Internal Medicine III, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Glueckstrasse 6, Erlangen 91054, Germany ) , Loskarn, Sandra (Department of Stem Cell Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Glueckstrasse 6, Erlangen 91054, Germany ) , Lie, Dieter Chichung (Emil-Fischer Centre, Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen 91054, Germany ) , Mielenz, Dirk (Department of Molecular Immunology, Department of Internal Medic) , Winner, Beate
    Stem cell reports v.10 no.2 ,pp. 347 - 355 , 2018 ,

    초록

    Summary Swiprosin-1/Efhd2 (Efhd2) is highly expressed in the CNS during development and in the adult. EFHD2 is regulated by Ca 2+ binding, stabilizes F-actin, and promotes neurite extension. Previous studies indicated a dysregulation of EFHD2 in human Alzheimer's disease brains. We hypothesized a detrimental effect of genetic ablation of Efhd2 on hippocampal integrity and specifically investigated adult hippocampal neurogenesis. Efhd2 was expressed throughout adult neuronal development and in mature neurons. We observed a severe reduction of the survival of adult newborn neurons in Efhd2 knockouts, starting at the early neuroblast stage. Spine formation and dendrite growth of newborn neurons were compromised in full Efhd2 knockouts, but not upon cell-autonomous Efhd2 deletion. Together with our finding of severe hippocampal tauopathy in Efhd2 knockout mice, these data connect Efhd2 to impaired synaptic plasticity as present in Alzheimer's disease and identify a role of Efhd2 in neuronal survival and synaptic integration in the adult hippocampus. Highlights • Efhd2 is expressed in the dentate gyrus and its loss reduces adult neurogenesis • Reduced neurite complexity and spine density in new neurons of Efhd2 knockout mice • Role of cell-extrinsic EFHD2 for dendrite morphology of adult newborn neurons • Increased levels of pathological TAU in the hippocampus of Efhd2 knockout mice In this report, Mielenz, Winner, and colleagues show a novel impact of Efhd2 on survival and integration of adult-born hippocampal neurons. This is of particular significance since EFHD2 regulates cytoskeletal transport and synaptic plasticity and since levels of pathological TAU are increased in Efhd2 knockout mice.

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    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  5. [해외논문]   Pathological Endogenous α-Synuclein Accumulation in Oligodendrocyte Precursor Cells Potentially Induces Inclusions in Multiple System Atrophy   SCIE

    Kaji, Seiji (Department of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, 606-8397 Kyoto, Japan ) , Maki, Takakuni (Department of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, 606-8397 Kyoto, Japan ) , Kinoshita, Hisanori (Department of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, 606-8397 Kyoto, Japan ) , Uemura, Norihito (Department of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, 606-8397 Kyoto, Japan ) , Ayaki, Takashi (Department of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, 606-8397 Kyoto, Japan ) , Kawamoto, Yasuhiro (Department of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, 606-8397 Kyoto, Japan ) , Furuta, Takahiro (Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan ) , Urushitani, Makoto (Department of Neurology, Shiga University of Medical Science, Otsu, 520-2192 Shiga, Japan ) , Hasegawa, Masato (Department of Dem) , Kinoshita, Yusuke , Ono, Yuichi , Mao, Xiaobo , Quach, Tran H. , Iwai, Kazuhiro , Dawson, Valina L. , Dawson, Ted M. , Takahashi, Ryosuke
    Stem cell reports v.10 no.2 ,pp. 356 - 365 , 2018 ,

    초록

    Summary Glial cytoplasmic inclusions (GCIs), commonly observed as α-synuclein (α-syn)-positive aggregates within oligodendrocytes, are the pathological hallmark of multiple system atrophy. The origin of α-syn in GCIs is uncertain; there is little evidence of endogenous α-syn expression in oligodendrocyte lineage cells, oligodendrocyte precursor cells (OPCs), and mature oligodendrocytes (OLGs). Here, based on in vitro analysis using primary rat cell cultures, we elucidated that preformed fibrils (PFFs) generated from recombinant human α-syn trigger multimerization and an upsurge of endogenous α-syn in OPCs, which is attributable to insufficient autophagic proteolysis. RNA-seq analysis of OPCs revealed that α-syn PFFs interfered with the expression of proteins associated with neuromodulation and myelination. Furthermore, we detected cytoplasmic α-syn inclusions in OLGs through differentiation of OPCs pre-incubated with PFFs. Overall, our findings suggest the possibility of endogenous α-syn accumulation in OPCs that contributes to GCI formation and perturbation of neuronal/glial support in multiple system atrophy brains. Highlights • Endogenous α-syn in OPCs drastically increases via seeding from exogenous α-syn PFFs • Exogenous α-syn PFFs do not induce SNCA mRNA overproduction but autophagic impairment • Exogenous α-syn PFFs compromise gene regulation for neuronal/glial modulation in OPCs • α-Syn PFF-treated OPCs differentiate into OLGs containing α-syn aggregates In this article, Maki and Takahashi report that the internalization of exogenous α-synuclein fibrils in oligodendrocyte precursor cells triggers misfolding and accumulation of endogenous α-synuclein via seeding mechanisms, which may eventually lead to neurodegeneration and myelin disruption in multiple system atrophy by compromising the oligodendroglial function of neuronal support and myelination.

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    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  6. [해외논문]   Astrocytes Attenuate Mitochondrial Dysfunctions in Human Dopaminergic Neurons Derived from iPSC   SCIE

    Du, Fang (Department of Pharmacology and Toxicology, and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, 2099 Constant Avenue, Lawrence, KS 66047, USA ) , Yu, Qing (Department of Pharmacology and Toxicology, and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, 2099 Constant Avenue, Lawrence, KS 66047, USA ) , Chen, Allen (Department of Pharmacology and Toxicology, and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, 2099 Constant Avenue, Lawrence, KS 66047, USA ) , Chen, Doris (Department of Pharmacology and Toxicology, and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, 2099 Constant Avenue, Lawrence, KS 66047, USA ) , ShiDu Yan, Shirley (Department of Pharmacology and Toxicology, and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, 2099 Constant Avenue, Lawrence, KS 66047, USA)
    Stem cell reports v.10 no.2 ,pp. 366 - 374 , 2018 ,

    초록

    Summary Astrocytes, the most populous glial cell type in the brain, are critical for regulating the brain microenvironment. In various neurodegenerative diseases, astrocytes determine the progression and outcome of the neuropathological process. We have recently revealed the direct involvement of mitochondrial function in human pluripotent stem cell (hiPSC)-derived dopaminergic (DA) neuronal differentiation. Using the astroglial-neuronal co-culture system, we show here that astrocytes effectively rescue defects in neurogenesis of DA neurons with mitochondrial respiratory chain disruption. Co-culture of astrocytes with defective DA neurons completely restored mitochondrial functions and dynamics insulted by mitochondrial toxins. These results suggest the significance of astroglia in maintaining mitochondrial development and bioenergetics during differentiation of hiPSC-derived DA neurons. Our study also provides an active astroglial-neuronal interaction model for future investigation of mitochondrial involvement in neurogenesis and neurodegenerative diseases. Highlights • Role of astrocyte on the development of hiPSC-derived dopaminergic neuron • Astrocyte protects dopaminergic neurogenesis by powering up mitochondrial respiration • Astrocyte restores mitochondrial function and dynamics in dopaminergic neuron • Evidence of astroglial and neuronal interaction during dopaminergic neurogenesis In this article, Shirley ShiDu Yan and colleagues show that human pluripotent stem cell-derived astrocytes effectively rescue defects in neurogenesis of dopaminergic neurons with mitochondrial respiratory chain disruption. Co-culture with astrocytes restored mitochondrial functions and dynamics in dopaminergic neurons insulted by mitochondrial toxins. These results provide evidence of astroglia in maintaining mitochondrial development and bioenergetics during dopaminergic neuronal differentiation.

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    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  7. [해외논문]   Isogenic FUS-eGFP iPSC Reporter Lines Enable Quantification of FUS Stress Granule Pathology that Is Rescued by Drugs Inducing Autophagy   SCIE

    Marrone, Lara (DFG-Center for Regenerative Therapies, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany ) , Poser, Ina (Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany ) , Casci, Ian (Department of Pediatrics, Division of Child Neurology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA ) , Japtok, Julia (Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany ) , Reinhardt, Peter (DFG-Center for Regenerative Therapies, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany ) , Janosch, Antje (Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany ) , Andree, Cordula (Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany ) , Lee, Hyun O. (Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany ) , Moebius, Claudia (Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany ) , Koerner, Ellen (DFG-Center for Regenerative Therapies, Technische Universität Dresden, Fetsch) , Reinhardt, Lydia , Cicardi, Maria Elena , Hackmann, Karl , Klink, Barbara , Poletti, Angelo , Alberti, Simon , Bickle, Marc , Hermann, Andreas , Pandey, Udai Bhan , Hyman, Anthony A. , Sterneckert, Jared L.
    Stem cell reports v.10 no.2 ,pp. 375 - 389 , 2018 ,

    초록

    Summary Perturbations in stress granule (SG) dynamics may be at the core of amyotrophic lateral sclerosis (ALS). Since SGs are membraneless compartments, modeling their dynamics in human motor neurons has been challenging, thus hindering the identification of effective therapeutics. Here, we report the generation of isogenic induced pluripotent stem cells carrying wild-type and P525L FUS-eGFP. We demonstrate that FUS-eGFP is recruited into SGs and that P525L profoundly alters their dynamics. With a screening campaign, we demonstrate that PI3K/AKT/mTOR pathway inhibition increases autophagy and ameliorates SG phenotypes linked to P525L FUS by reducing FUS-eGFP recruitment into SGs. Using a Drosophila model of FUS-ALS, we corroborate that induction of autophagy significantly increases survival. Finally, by screening clinically approved drugs for their ability to ameliorate FUS SG phenotypes, we identify a number of brain-penetrant anti-depressants and anti-psychotics that also induce autophagy. These drugs could be repurposed as potential ALS treatments. Highlights • Generation of isogenic WT and P525L FUS-eGFP reporter iPSCs • P525L FUS-eGFP SGs are more numerous, more intense, and larger than WT • Increasing PI3K/AKT/mTOR-regulated autophagy reduces FUS-eGFP recruitment to SGs • Brain-penetrant drugs that induce autophagy ameliorate the FUS SG phenotype Sterneckert and colleagues generate isogenic FUS-eGFP reporter iPSCs that enable the identification of stress granule (SG) phenotypes specifically induced by the ALS mutation FUS P525L. Compound screening shows that modulation of the PI3K/AKT/mTOR pathway regulating autophagy ameliorates SG phenotypes. A second screen identifies similarly acting brain-penetrant US FDA-approved drugs that could be repurposed to treat ALS.

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  8. [해외논문]   Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem Cells   SCIE

    Gupta, Sandeep (Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095, USA ) , Sivalingam, Daniel (Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095, USA ) , Hain, Samantha (Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095, USA ) , Makkar, Christian (Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095, USA ) , Sosa, Enrique (Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA ) , Clark, Amander (Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA ) , Butler, Samantha J. (Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095, USA)
    Stem cell reports v.10 no.2 ,pp. 390 - 405 , 2018 ,

    초록

    Summary Cellular replacement therapies for neurological conditions use human embryonic stem cell (hESC)- or induced pluripotent stem cell (hiPSC)-derived neurons to replace damaged or diseased populations of neurons. For the spinal cord, significant progress has been made generating the in-vitro -derived motor neurons required to restore coordinated movement. However, there is as yet no protocol to generate in-vitro -derived sensory interneurons (INs), which permit perception of the environment. Here, we report on the development of a directed differentiation protocol to derive sensory INs for both hESCs and hiPSCs. Two developmentally relevant factors, retinoic acid in combination with bone morphogenetic protein 4, can be used to generate three classes of sensory INs: the proprioceptive dI1s, the dI2s, and mechanosensory dI3s. Critical to this protocol is the competence state of the neural progenitors, which changes over time. This protocol will facilitate developing cellular replacement therapies to reestablish sensory connections in injured patients. Highlights • Robust protocol to generate spinal sensory neurons from human pluripotent cells • RA ± BMP4 direct hPSCs toward the dI1, dI2, and dI3 classes of dorsal interneurons • Only neural progenitors in the correct competence state respond to RA/BMP4 signals In this article, Gupta and colleagues describe a robust protocol to derive spinal dorsal sensory interneurons from human pluripotent stem cells using the sequential addition of RA and BMP4. They find that neural progenitors must be in the correct competence state to respond to RA/BMP4 as dorsalizing signals. This competence state changes over time and determines the efficiency of the protocol.

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    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  9. [해외논문]   Transplanted Donor- or Stem Cell-Derived Cone Photoreceptors Can Both Integrate and Undergo Material Transfer in an Environment-Dependent Manner   SCIE

    Waldron, Paul V. (UCL Institute of Ophthalmology, 11–43 Bath Street, London EC1V 9EL, UK ) , Di Marco, Fabiana (Stem Cells and Regenerative Medicine Section, UCL Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK ) , Kruczek, Kamil (UCL Institute of Ophthalmology, 11–43 Bath Street, London EC1V 9EL, UK ) , Ribeiro, Joana (UCL Institute of Ophthalmology, 11–43 Bath Street, London EC1V 9EL, UK ) , Graca, Anna B. (UCL Institute of Ophthalmology, 11–43 Bath Street, London EC1V 9EL, UK ) , Hippert, Claire (UCL Institute of Ophthalmology, 11–43 Bath Street, London EC1V 9EL, UK ) , Aghaizu, Nozie D. (UCL Institute of Ophthalmology, 11–43 Bath Street, London EC1V 9EL, UK ) , Kalargyrou, Aikaterini A. (UCL Institute of Ophthalmology, 11–43 Bath Street, London EC1V 9EL, UK ) , Barber, Amanda C. (UCL Institute of Ophthalmology, 11–43 Bath Street, London EC1V 9EL, UK ) , Grimaldi, Giulia (Stem Cells and Regenerative Medicine Section, UCL Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK ) , Duran, Yanai (UCL Institute of Ophthalmolo) , Blackford, Samuel J.I. , Kloc, Magdalena , Goh, Debbie , Zabala Aldunate, Eduardo , Sampson, Robert D. , Bainbridge, James W.B. , Smith, Alexander J. , Gonzalez-Cordero, Anai , Sowden, Jane C. , Ali, Robin R. , Pearson, Rachael A.
    Stem cell reports v.10 no.2 ,pp. 406 - 421 , 2018 ,

    초록

    Summary Human vision relies heavily upon cone photoreceptors, and their loss results in permanent visual impairment. Transplantation of healthy photoreceptors can restore visual function in models of inherited blindness, a process previously understood to arise by donor cell integration within the host retina. However, we and others recently demonstrated that donor rod photoreceptors engage in material transfer with host photoreceptors, leading to the host cells acquiring proteins otherwise expressed only by donor cells. We sought to determine whether stem cell- and donor-derived cones undergo integration and/or material transfer. We find that material transfer accounts for a significant proportion of rescued cells following cone transplantation into non-degenerative hosts. Strikingly, however, substantial numbers of cones integrated into the Nrl −/− and Prph2 rd2/rd2 , but not Nrl −/− ; RPE65 R91W/R91W , murine models of retinal degeneration. This confirms the occurrence of photoreceptor integration in certain models of retinal degeneration and demonstrates the importance of the host environment in determining transplantation outcome. Highlights • Transplanted cone photoreceptors can incorporate into host retina • Transplanted cone photoreceptors undergo material transfer with host photoreceptors • Host retinas with disrupted cytoarchitecture facilitate cone incorporation • Host environment affects relative contributions of integration and material transfer Pearson and colleagues demonstrate that transplanted cone photoreceptors can both undergo incorporation into the host neural retina and engage in cytoplasmic material transfer with host rod and cone photoreceptors. They show that the host environment plays a crucial role in determining the relative contributions of these two mechanisms to transplantation outcome.

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  10. [해외논문]   Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells   SCIE

    Chin, Chee Jia (Department of Pathology and Laboratory Medicine, David Geffen School of Medicine (DGSOM), University of California (UCLA), Los Angeles, CA 90095, USA ) , Li, Suwen (Department of Pathology and Laboratory Medicine, David Geffen School of Medicine (DGSOM), University of California (UCLA), Los Angeles, CA 90095, USA ) , Corselli, Mirko (Becton Dickinson, San Diego, CA 92121, USA ) , Casero, David (Department of Pathology and Laboratory Medicine, David Geffen School of Medicine (DGSOM), University of California (UCLA), Los Angeles, CA 90095, USA ) , Zhu, Yuhua (Department of Pathology and Laboratory Medicine, David Geffen School of Medicine (DGSOM), University of California (UCLA), Los Angeles, CA 90095, USA ) , He, Chong Bin (Department of Pathology and Laboratory Medicine, David Geffen School of Medicine (DGSOM), University of California (UCLA), Los Angeles, CA 90095, USA ) , Hardy, Reef (Department of Orthopedics, DGSOM, UCLA, Los Angeles, CA 90095, USA ) , Pé (Department of Pathology and Laboratory Medicine, David Geffen School of Medicine (DGSOM), University of California (UCLA), Los) , ault, Bruno , Crooks, Gay M.
    Stem cell reports v.10 no.2 ,pp. 436 - 446 , 2018 ,

    초록

    Summary Various mesenchymal cell types have been identified as critical components of the hematopoietic stem/progenitor cell (HSPC) niche. Although several groups have described the generation of mesenchyme from human pluripotent stem cells (hPSCs), the capacity of such cells to support hematopoiesis has not been reported. Here, we demonstrate that distinct mesenchymal subpopulations co-emerge from mesoderm during hPSC differentiation. Despite co-expression of common mesenchymal markers (CD73, CD105, CD90, and PDGFRβ), a subset of cells defined as CD146 hi CD73 hi expressed genes associated with the HSPC niche and supported the maintenance of functional HSPCs ex vivo, while CD146 lo CD73 lo cells supported differentiation. Stromal support of HSPCs was contact dependent and mediated in part through high JAG1 expression and low WNT signaling. Molecular profiling revealed significant transcriptional similarity between hPSC-derived CD146 ++ and primary human CD146 ++ perivascular cells. The derivation of functionally diverse types of mesenchyme from hPSCs opens potential avenues to model the HSPC niche and develop PSC-based therapies. Highlights • hPSCs generated functionally and transcriptionally distinct mesenchymal populations • CD146 hi CD73 hi mesenchyme expressed HSC niche genes and supported human HSPCs ex vivo • CD146 lo CD73 lo mesenchyme drove HSPC differentiation • CD146 hi CD73 hi mesenchyme shared a transcriptome profile with human pericytes Crooks and colleagues demonstrated a previously underappreciated functional and molecular heterogeneity in mesenchyme generated from human pluripotent stem cells. Two mesenchymal subsets were distinguished by the reciprocal expression of CD146, CD73, and CD140a. CD146 hi CD73 hi mesenchyme supported self-renewing hematopoietic stem and progenitor cells (HSPCs), expressed markers of the HSPC niche, and shared a similar molecular signature with primary human adult pericytes.

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