Mechanisms of iPS cell generation and beyond.

Mechanisms of iPS cell generation and beyond. Keio J Med. 2017;66(1):14 Authors: Kaji K Abstract The generation of induced pluripotent stem cells (iPSCs) achieved by overexpression of Oct4, Sox2, Klf4 and c-Myc, transformed our classical views of the cellular epigenetic landscape and delivered a new concept for cell and tissue engineering. In addition to iPSCs, several other cell types have also been generated by master transcription factor (TF)-mediated transdifferentiation. However, the critical molecular mechanisms amongst diverse cellular identity changes are not well understood. Through the investigation of reprogramming mechanisms, we recently revealed that over-expression of constitutive active Smad3 boosted not only iPSC generation, but also 3 other master TF-mediated conversions, from B cells to macrophages, myoblasts to adipocytes, and human fibroblasts to neurons. This demonstrated that there were common mechanisms underlying different master TF-mediated cell conversions. To illuminate such mechanisms further, we have recently performed CRISPR/Cas9-mediated genome-wide knockout screening during reprogramming with a lentiviral gRNA library containing 90,000 gRNAs. This screening provided us with ~15 novel reprogramming roadblock genes as well as ~20 candidate genes essential for the reprogramming process but not for ES cell self-renewal. This data set will be a valuable resource to further understand how overexpression of master TFs alters cell...
Source: The Keio Journal of Medicine - Category: Universities & Medical Training Authors: Tags: Keio J Med Source Type: research

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Authors: Gomes I, de Almeida BP, Dâmaso S, Mansinho A, Correia I, Henriques S, Cruz-Duarte R, Vilhais G, Félix P, Alves P, Corredeira P, Barbosa-Morais NL, Costa L, Casimiro S Abstract The role of RANKL-RANK pathway in progesterone-driven mammary carcinogenesis and triple negative breast cancer tumorigenesis has been well characterized. However, and despite evidences of the existence of RANK-positive hormone receptor (HR)-positive breast tumors, the implication of RANK expression in HR-positive breast cancers has not been addressed before. Here, we report that RANK pathway affects the expression of cel...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Authors: Kapoor V, Collins A, Griffith K, Ghosh S, Wong N, Wang X, Challen GA, Krambs J, Link D, Hallahan DE, Thotala D Abstract The immune system plays a vital role in cancer therapy, especially with the advent of immunotherapy. Radiation therapy induces iatrogenic immunosuppression referred to as radiation-induced lymphopenia (RIL). RIL correlates with significant decreases in the overall survival of cancer patients. Although the etiology and severity of lymphopenia are known, the mechanism(s) of RIL are largely unknown. We found that irradiation not only had direct effects on circulating lymphocytes but also had...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
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Source: Stem Cell Research - Category: Stem Cells Source Type: research
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Source: Stem Cell Research - Category: Stem Cells Source Type: research
Authors: Feld J, Belasen A, Navada SC Abstract INTRODUCTION: Myelodysplastic syndromes (MDS) represent a range of bone marrow disorders, with patients affected by cytopenias and risk of progression to AML. There are limited therapeutic options available for patients, including hypomethylating agents (azacitidine/decitabine), growth factor support, lenalidomide, and allogeneic stem cell transplant. AREAS COVERED: This review provides an overview of the progress made over the past decade for emerging therapies for lower- and higher-risk MDS (MDS-HR). We also cover advances in prognostication, supportive care, and...
Source: Expert Review of Anticancer Therapy - Category: Cancer & Oncology Tags: Expert Rev Anticancer Ther Source Type: research
Authors: Kallam A, Armitage JO Abstract INTRODUCTION: T cell lymphomas are a heterogeneous group, with varying incidences, geographic patterns, and risk factors. Although until recently approached in a manner similar to B cell lymphomas, the treatment outcomes are poor and this disease is characterized by high relapse rates. The treatment advances in PTCL have been slow compared to B cell lymphomas. The outcomes of patients who progress following stem cell transplantation are worse. AREAS COVERED: This review focuses on the novel targeted agents that are approved and/or are under investigation for patients with...
Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research
Aging as we understand it is almost a universal phenomenon in animals. Clearly there is something advantageous in evolutionary terms in having disposable individuals carry the immortal germline forward in time. One possibility is that aging is an emergent property of the fact that selection pressure is always going to fall more heavily on younger individuals, and thus evolution favors change in the direction of biological systems that are highly effective in youth but fall apart later on. Resources directed towards long-term maintenance subtract from resources directed towards immediate reproductive success. It is a brutal...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
Funding Opportunity RFA-HL-21-003 from the NIH Guide for Grants and Contracts. The National Institutes of Health (NIH) participating Institutes and Centers, in coordination with the U.S. Food and Drug Administration (FDA), seeks highly meritorious clinical trial applications proposing to explore and enable the development of safe and effective regenerative medicine (RM) interventions using adult stem cells. This Funding Opportunity Announcement (FOA), issued as part of the Regenerative Medicine Innovation Project (RMIP), represents one step in fulfilling a statutory provision set forth in the 21st Century Cures Act. Appli...
Source: NIH Funding Opportunities (Notices, PA, RFA) - Category: Research Source Type: funding
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