Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation Potential

Reports on the retention of somatic cell memory in induced pluripotent stem cells (iPSCs) have complicated the selection of the optimal cell type for the generation of iPSC biobanks. To address this issue we compared transcriptomic, epigenetic, and differentiation propensities of genetically matched human iPSCs derived from fibroblasts and blood, two tissues of the most practical relevance for biobanking. Our results show that iPSC lines derived from the same donor are highly similar to each other. However, genetic variation imparts a donor-specific expression and methylation profile in reprogrammed cells that leads to variable functional capacities of iPSC lines. Our results suggest that integration-free, bona fide iPSC lines from fibroblasts and blood can be combined in repositories to form biobanks. Due to the impact of genetic variation on iPSC differentiation, biobanks should contain cells from large numbers of donors.Peer reviewe

Mid-Infrared Conductivity from Mid-Gap States Associated with Charge Stripes

The optical conductivity of La(2-x)Sr(x)NiO(4) has been interpreted in various ways, but so far the proposed interpretations have neglected the fact that the holes doped into the NiO(2) planes order in diagonal stripes, as established by neutron and X-ray scattering. Here we present a study of optical conductivity in La(2)NiO(4+d) with d=2/15, a material in which the charge stripes order three-dimensionally. We show that the conductivity can be decomposed into two components, a mid-infrared peak that we attribute to transitions from the filled valence band into empty mid-gap states associated with the stripes, and a Drude peak that appears at higher temperatures as carriers are thermally excited into the mid-gap states. The shift of the mid-IR peak to lower energy with increasing temperature is explained in terms of the Franck-Condon effect. The relevance of these results to understanding the optical conductivity in the cuprates is discussed.Comment: final version of paper (minor changes from previous version

Angle-resolved photoemission spectroscopy of the cuprate superconductors

This paper reviews the most recent ARPES results on the cuprate superconductors and their insulating parent and sister compounds, with the purpose of providing an updated summary of the extensive literature in this field. The low energy excitations are discussed with emphasis on some of the most relevant issues, such as the Fermi surface and remnant Fermi surface, the superconducting gap, the pseudogap and d-wave-like dispersion, evidence of electronic inhomogeneity and nano-scale phase separation, the emergence of coherent quasiparticles through the superconducting transition, and many-body effects in the one-particle spectral function due to the interaction of the charge with magnetic and/or lattice degrees of freedom. The first part of the paper introduces photoemission spectroscopy in the context of strongly interacting systems, along with an update on the state-of-the-art instrumentation. The second part provides a brief overview of the scientific issues relevant to the investigation of the low energy electronic structure by ARPES. The rest of the paper is devoted to the review of experimental results from the cuprates and the discussion is organized along conceptual lines: normal-state electronic structure, interlayer interaction, superconducting gap, coherent superconducting peak, pseudogap, electron self energy and collective modes. Within each topic, ARPES data from the various copper oxides are presented.Comment: Reviews of Modern Physics, in press. A HIGH-QUALITY pdf file is available at http://www.physics.ubc.ca/~damascel/RMP_ARPES.pd

Block copolymers for optical nanowriting and data storage: dynamic responses and matrix heterogeneity over different length- and time-scales

Showing the list of differentially expressed genes between TAF-MSCs and CB-Endo cells. TAF-MSCs term amniotic fluid-derived MSCs, CB-Endo cells cord blood-derived endothelial cells. (XLSX 4454 kb

Molecular Mechanisms Responsible for Anti-inflammatory and Immunosuppressive Effects of Mesenchymal Stem Cell-Derived Factors.

Mesenchymal stem cells (MSCs) are self-renewable cells capable for multilineage differentiation and immunomodulation. MSCs are able to differentiate into all cell types of mesodermal origin and, due to their plasticity, may generate cells of neuroectodermal or endodermal origin in vitro. In addition to the enormous differentiation potential, MSCs efficiently modulate innate and adaptive immune response and, accordingly, were used in large number of experimental and clinical trials as new therapeutic agents in regenerative medicine. Although MSC-based therapy was efficient in the treatment of many inflammatory and degenerative diseases, unwanted differentiation of engrafted MSCs represents important safety concern. MSC-based beneficial effects are mostly relied on the effects of MSC-derived immunomodulatory, pro-angiogenic, and trophic factors which attenuate detrimental immune response and inflammation, reduce ischemic injuries, and promote tissue repair and regeneration. Accordingly, MSC-conditioned medium (MSC-CM), which contains MSC-derived factors, has the potential to serve as a cell-free, safe therapeutic agent for the treatment of inflammatory diseases. Herein, we summarized current knowledge regarding identification, isolation, ontogeny, and functional characteristics of MSCs and described molecular mechanisms responsible for MSC-CM-mediated anti-inflammatory and immunosuppressive effects in the therapy of inflammatory lung, liver, and kidney diseases and ischemic brain injury

Comparison of the Regenerative Potential for Lung Tissue of Mesenchymal Stromal Cells from Different Sources/Locations Within the Body

To date, bone marrow-derived mesenchymal stromal cells (MSCs) have been considered the golden standard among MSC cell-based therapies. However, the harvesting of bone marrow is a highly invasive procedure and the number of MSCs isolated is low, and it declines with increasing age. MSCs with immune-regulatory and regenerative properties can be isolated from many different tissues; however, bone marrow-derived MSCs are so far the most thoroughly characterized MSC population. Despite an increased interest in using MSCs for clinical approaches in severe lung disorders, the biological function of MSCs after administration is not completely known, in particular, of MSCs extracted from other tissues than bone marrow aspirates. MSCs do not engraft after infusion, and data demonstrate that the majority of MSCs tend to be cleared from the lungs within a few days, suggesting a fast, short acting, and paracrine effect. Following activation, MSCs produce and secrete mediators, the secretome, that influence the microenvironment and the surrounding resident cells in order to modulate and repair damaged tissue. Exploring the MSC secretome has attracted much attention, and today it is known to consist of an array of molecules that is important for their regenerative and protective abilities. However, recent data suggest that the secretome profiles differ significantly depending on the MSC source, donor site, and external stimulation. In addition, the microenvironment that the infused MSCs encounter most likely plays an important role in influencing the therapeutic effect of MSCs. The composition of the microenvironment is unique in every tissue type and varies by developmental age. Changes in both stiffness and composition drastically affect MSC fate and function. The aim of this chapter is to provide a comparison of the potential of MSCs obtained from different cellular sources, and how they can be used as therapeutic agents to treat lung disorders