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Article ; Online: Reducing Mcl-1 gene dosage induces dopaminergic neuronal loss and motor impairments in Park2 knockout mice

Susanna Ekholm-Reed / Robert Baker / Alexandre R. Campos / David Stouffer / Martha Henze / Dieter A. Wolf / Jeanne F. Loring / Elizabeth A. Thomas / Steven I. Reed

Communications Biology, Vol 2, Iss 1, Pp 1-

2019 Volume 7

Abstract: Susanna Ekholm-Reed et al. develop a Parkinson mouse model by reducing Mcl-1 gene dosage by half, which leads to dopaminergic cell loss and motor impairments in Park2 knockout mice that otherwise do not exhibit any of the hallmark phenotypes associated ... ...

Abstract	Susanna Ekholm-Reed et al. develop a Parkinson mouse model by reducing Mcl-1 gene dosage by half, which leads to dopaminergic cell loss and motor impairments in Park2 knockout mice that otherwise do not exhibit any of the hallmark phenotypes associated with Parkinson’s disease.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2019-04-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Human Pluripotent Stem Cell-Derived Multipotent Vascular Progenitors of the Mesothelium Lineage Have Utility in Tissue Engineering and Repair

Thomas Colunga / Miranda Hayworth / Sebastian Kreß / David M. Reynolds / Luoman Chen / Kristopher L. Nazor / Johannes Baur / Amar M. Singh / Jeanne F. Loring / Marco Metzger / Stephen Dalton

Cell Reports, Vol 26, Iss 10, Pp 2566-2579.e

2019 Volume 10

Abstract: Summary: In this report we describe a human pluripotent stem cell-derived vascular progenitor (MesoT) cell of the mesothelium lineage. MesoT cells are multipotent and generate smooth muscle cells, endothelial cells, and pericytes and self-assemble into ... ...

Abstract	Summary: In this report we describe a human pluripotent stem cell-derived vascular progenitor (MesoT) cell of the mesothelium lineage. MesoT cells are multipotent and generate smooth muscle cells, endothelial cells, and pericytes and self-assemble into vessel-like networks in vitro. MesoT cells transplanted into mechanically damaged neonatal mouse heart migrate into the injured tissue and contribute to nascent coronary vessels in the repair zone. When seeded onto decellularized vascular scaffolds, MesoT cells differentiate into the major vascular lineages and self-assemble into vasculature capable of supporting peripheral blood flow following transplantation. These findings demonstrate in vivo functionality and the potential utility of MesoT cells in vascular engineering applications. : Colunga et al. describe a multipotent vascular progenitor cell that contributes to neovascularization of damaged tissue and that efficiently populates vascular scaffolds and self-assembles into functional vessels. These findings open up new opportunities for the vascularization of diseased and damaged tissue and for surgical vessel replacement. Keywords: stem cells, mesothelium, vascular progenitor, tissue engineering, regenerative medicine
Keywords	Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Author Correction

Chen Chen / Peng Jiang / Haipeng Xue / Suzanne E. Peterson / Ha T. Tran / Anna E. McCann / Mana M. Parast / Shenglan Li / David E. Pleasure / Louise C. Laurent / Jeanne F. Loring / Ying Liu / Wenbin Deng

Nature Communications, Vol 11, Iss 1, Pp 1-

Role of astroglia in Down’s syndrome revealed by patient-derived human-induced pluripotent stem cells

2020 Volume 1

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

Abstract	An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Keywords	Science ; Q
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Remyelination Is Correlated with Regulatory T Cell Induction Following Human Embryoid Body-Derived Neural Precursor Cell Transplantation in a Viral Model of Multiple Sclerosis.

Warren C Plaisted / Angel Zavala / Edna Hingco / Ha Tran / Ronald Coleman / Thomas E Lane / Jeanne F Loring / Craig M Walsh

PLoS ONE, Vol 11, Iss 6, p e

2016 Volume 0157620

Abstract: We have recently described sustained clinical recovery associated with dampened neuroinflammation and remyelination following transplantation of neural precursor cells (NPCs) derived from human embryonic stem cells (hESCs) in a viral model of the human ... ...

Abstract	We have recently described sustained clinical recovery associated with dampened neuroinflammation and remyelination following transplantation of neural precursor cells (NPCs) derived from human embryonic stem cells (hESCs) in a viral model of the human demyelinating disease multiple sclerosis. The hNPCs used in that study were derived by a novel direct differentiation method (direct differentiation, DD-NPCs) that resulted in a unique gene expression pattern when compared to hNPCs derived by conventional methods. Since the therapeutic potential of human NPCs may differ greatly depending on the method of derivation and culture, we wanted to determine whether NPCs differentiated using conventional methods would be similarly effective in improving clinical outcome under neuroinflammatory demyelinating conditions. For the current study, we utilized hNPCs differentiated from a human induced pluripotent cell line via an embryoid body intermediate stage (EB-NPCs). Intraspinal transplantation of EB-NPCs into mice infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) resulted in decreased accumulation of CD4+ T cells in the central nervous system that was concomitant with reduced demyelination at the site of injection. Dampened neuroinflammation and remyelination was correlated with a transient increase in CD4+FOXP3+ regulatory T cells (Tregs) concentrated within the peripheral lymphatics. However, compared to our earlier study, pathological improvements were modest and did not result in significant clinical recovery. We conclude that the genetic signature of NPCs is critical to their effectiveness in this model of viral-induced neurologic disease. These comparisons will be useful for understanding what factors are critical for the sustained clinical improvement.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Whole-genome mutational burden analysis of three pluripotency induction methods

Kunal Bhutani / Kristopher L. Nazor / Roy Williams / Ha Tran / Heng Dai / Željko Džakula / Edward H. Cho / Andy W. C. Pang / Mahendra Rao / Han Cao / Nicholas J. Schork / Jeanne F. Loring

Nature Communications, Vol 7, Iss 1, Pp 1-

2016 Volume 8

Abstract: It is feared that reprogramming may introduce DNA mutations. Here Bhutani et al. take three different reprogramming methods and using comparative whole genome analyses do identify nucleotide variations that are different in reprogrammed cells from the ... ...

Abstract	It is feared that reprogramming may introduce DNA mutations. Here Bhutani et al. take three different reprogramming methods and using comparative whole genome analyses do identify nucleotide variations that are different in reprogrammed cells from the original fibroblasts, but none convey oncogenic potential.
Keywords	Science ; Q
Language	English
Publishing date	2016-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis

Lu Chen / Ronald Coleman / Ronika Leang / Ha Tran / Alexandra Kopf / Craig M. Walsh / Ilse Sears-Kraxberger / Oswald Steward / Wendy B. Macklin / Jeanne F. Loring / Thomas E. Lane

Stem Cell Reports, Vol 2, Iss 6, Pp 825-

2014 Volume 837

Abstract: Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not ... ...

Abstract	Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4+CD25+FOXP3+ regulatory T cells (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments.
Keywords	Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2014-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Standard Nomenclature for Referencing and Authentication of Pluripotent Stem Cells

Andreas Kurtz / Stefanie Seltmann / Amos Bairoch / Marie-Sophie Bittner / Kevin Bruce / Amanda Capes-Davis / Laura Clarke / Jeremy M. Crook / Laurence Daheron / Johannes Dewender / Adam Faulconbridge / Wataru Fujibuchi / Alexander Gutteridge / Derek J. Hei / Yong-Ou Kim / Jung-Hyun Kim / Anja Kolb- Kokocinski / Fritz Lekschas / Geoffrey P. Lomax /

Jeanne F. Loring / Tenneille Ludwig / Nancy Mah / Tohru Matsui / Robert Müller / Helen Parkinson / Michael Sheldon / Kelly Smith / Harald Stachelscheid / Glyn Stacey / Ian Streeter / Anna Veiga / Ren-He Xu

Stem Cell Reports, Vol 10, Iss 1, Pp 1-

2018 Volume 6

Abstract: Unambiguous cell line authentication is essential to avoid loss of association between data and cells. The risk for loss of references increases with the rapidity that new human pluripotent stem cell (hPSC) lines are generated, exchanged, and implemented. ...

Abstract	Unambiguous cell line authentication is essential to avoid loss of association between data and cells. The risk for loss of references increases with the rapidity that new human pluripotent stem cell (hPSC) lines are generated, exchanged, and implemented. Ideally, a single name should be used as a generally applied reference for each cell line to access and unify cell-related information across publications, cell banks, cell registries, and databases and to ensure scientific reproducibility. We discuss the needs and requirements for such a unique identifier and implement a standard nomenclature for hPSCs, which can be automatically generated and registered by the human pluripotent stem cell registry (hPSCreg). To avoid ambiguities in PSC-line referencing, we strongly urge publishers to demand registration and use of the standard name when publishing research based on hPSC lines.
Keywords	human pluripotent stem cells ; cell line nomenclature ; cell data referencing ; cell line authentication ; cell databases ; stem cell registry ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Evidence that gene activation and silencing during stem cell differentiation requires a transcriptionally paused intermediate state.

Jonathan L Golob / Roshan M Kumar / Matthew G Guenther / Lil M Pabon / Gabriel A Pratt / Jeanne F Loring / Louise C Laurent / Richard A Young / Charles E Murry

PLoS ONE, Vol 6, Iss 8, p e

2011 Volume 22416

Abstract: A surprising portion of both mammalian and Drosophila genomes are transcriptionally paused, undergoing initiation without elongation. We tested the hypothesis that transcriptional pausing is an obligate transition state between definitive activation and ... ...

Abstract	A surprising portion of both mammalian and Drosophila genomes are transcriptionally paused, undergoing initiation without elongation. We tested the hypothesis that transcriptional pausing is an obligate transition state between definitive activation and silencing as human embryonic stem cells (hESCs) change state from pluripotency to mesoderm. Chromatin immunoprecipitation for trimethyl lysine 4 on histone H3 (ChIP-Chip) was used to analyze transcriptional initiation, and 3' transcript arrays were used to determine transcript elongation. Pluripotent and mesodermal cells had equivalent fractions of the genome in active and paused transcriptional states (∼48% each), with ∼4% definitively silenced (neither initiation nor elongation). Differentiation to mesoderm changed the transcriptional state of 12% of the genome, with roughly equal numbers of genes moving toward activation or silencing. Interestingly, almost all loci (98-99%) changing transcriptional state do so either by entering or exiting the paused state. A majority of these transitions involve either loss of initiation, as genes specifying alternate lineages are archived, or gain of initiation, in anticipation of future full-length expression. The addition of chromatin dynamics permitted much earlier predictions of final cell fate compared to sole use of conventional transcript arrays. These findings indicate that the paused state may be the major transition state for genes changing expression during differentiation, and implicate control of transcriptional elongation as a key checkpoint in lineage specification.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome.

Steven D Sheridan / Kraig M Theriault / Surya A Reis / Fen Zhou / Jon M Madison / Laurence Daheron / Jeanne F Loring / Stephen J Haggarty

PLoS ONE, Vol 6, Iss 10, p e

2011 Volume 26203

Abstract: Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. In addition to cognitive deficits, FXS patients exhibit hyperactivity, attention deficits, social difficulties, anxiety, and other autistic-like behaviors. FXS is ... ...

Abstract	Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. In addition to cognitive deficits, FXS patients exhibit hyperactivity, attention deficits, social difficulties, anxiety, and other autistic-like behaviors. FXS is caused by an expanded CGG trinucleotide repeat in the 5' untranslated region of the Fragile X Mental Retardation (FMR1) gene leading to epigenetic silencing and loss of expression of the Fragile X Mental Retardation protein (FMRP). Despite the known relationship between FMR1 CGG repeat expansion and FMR1 silencing, the epigenetic modifications observed at the FMR1 locus, and the consequences of the loss of FMRP on human neurodevelopment and neuronal function remain poorly understood. To address these limitations, we report on the generation of induced pluripotent stem cell (iPSC) lines from multiple patients with FXS and the characterization of their differentiation into post-mitotic neurons and glia. We show that clones from reprogrammed FXS patient fibroblast lines exhibit variation with respect to the predominant CGG-repeat length in the FMR1 gene. In two cases, iPSC clones contained predominant CGG-repeat lengths shorter than measured in corresponding input population of fibroblasts. In another instance, reprogramming a mosaic patient having both normal and pre-mutation length CGG repeats resulted in genetically matched iPSC clonal lines differing in FMR1 promoter CpG methylation and FMRP expression. Using this panel of patient-specific, FXS iPSC models, we demonstrate aberrant neuronal differentiation from FXS iPSCs that is directly correlated with epigenetic modification of the FMR1 gene and a loss of FMRP expression. Overall, these findings provide evidence for a key role for FMRP early in human neurodevelopment prior to synaptogenesis and have implications for modeling of FXS using iPSC technology. By revealing disease-associated cellular phenotypes in human neurons, these iPSC models will aid in the discovery of novel therapeutics for FXS and other ...
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Equivalence of conventionally-derived and parthenote-derived human embryonic stem cells.

Julie V Harness / Nikolay A Turovets / Magdalene J Seiler / Gabriel Nistor / Gulsah Altun / Larissa S Agapova / David Ferguson / Louise C Laurent / Jeanne F Loring / Hans S Keirstead

PLoS ONE, Vol 6, Iss 1, p e

2011 Volume 14499

Abstract: As human embryonic stem cell (hESC) lines can be derived via multiple means, it is important to determine particular characteristics of individual lines that may dictate the applications to which they are best suited. The objective of this work was to ... ...

Abstract	As human embryonic stem cell (hESC) lines can be derived via multiple means, it is important to determine particular characteristics of individual lines that may dictate the applications to which they are best suited. The objective of this work was to determine points of equivalence and differences between conventionally-derived hESC and parthenote-derived hESC lines (phESC) in the undifferentiated state and during neural differentiation.hESC and phESC were exposed to the same expansion conditions and subsequent neural and retinal pigmented epithelium (RPE) differentiation protocols. Growth rates and gross morphology were recorded during expansion. RTPCR for developmentally relevant genes and global DNA methylation profiling were used to compare gene expression and epigenetic characteristics. Parthenote lines proliferated more slowly than conventional hESC lines and yielded lower quantities of less mature differentiated cells in a neural progenitor cell (NPC) differentiation protocol. However, the cell lines performed similarly in a RPE differentiation protocol. The DNA methylation analysis showed similar general profiles, but the two cell types differed in methylation of imprinted genes. There were no major differences in gene expression between the lines before differentiation, but when differentiated into NPCs, the two cell types differed in expression of extracellular matrix (ECM) genes.These data show that hESC and phESC are similar in the undifferentiated state, and both cell types are capable of differentiation along neural lineages. The differences between the cell types, in proliferation and extent of differentiation, may be linked, in part, to the observed differences in ECM synthesis and methylation of imprinted genes.
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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