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Pulmonary Cell News| ESC & iPSC News 13.23 June 13, 2018 | |
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TOP STORYp53 Inhibits CRISPR-Cas9 Engineering in Human Pluripotent Stem Cells Using human PSC (hPSC) lines with stable integration of Cas9 or transient delivery of Cas9-ribonucleoproteins, researchers achieved an average insertion or deletion (indel) efficiency greater than 80%. This high efficiency of indel generation revealed that double-strand breaks (DSBs) induced by Cas9 were toxic and killed most hPSCs. The toxic response to DSBs was P53/TP53-dependent, such that the efficiency of precise genome engineering in hPSCs with a wild-type P53 gene was severely reduced. [Nat Med] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)GATA6 Suppression Enhances Lung Specification from Human Pluripotent Stem Cells Scientists found that the human stem cell lines most efficient at generating NKX2.1+ lung progenitors expressed lower endogenous levels of GATA6 during endoderm patterning and that knockdown of GATA6 during endoderm patterning increased the generation of these cells. [J Clin Invest] Full Article Activated signaling and growth of PTPN11 iPSCs were preferentially inhibited in vitro by the MEKi PD0325901 and trametinib. Conversely, JAK/STAT signaling was selectively activated in CBL iPSCs and abrogated by the JAKi momelotinib and ruxolitinib. The PI3Kδi idelalisib and mTORi rapamycin inhibited signaling and myeloproliferation in both PTPN11 and CBL iPSCs. [Leukemia] Abstract Silencing of leucine-rich repeat neuronal protein 1 (LRRN1) with short hairpin RNA (shLRRN1) in human ESCs resulted in decreased capacity of self-renewal, and skewed differentiation toward endoderm/mesoderm lineages in vitro and in vivo. The protein expression levels of the pluripotency factors OCT4, NANOG and SOX2 were reduced. [Stem Cells] Abstract The authors showed that human iPSCs have elevated basal levels of γH2AX which correlated with markers of DNA replication: EdU and the single-strand binding protein, RPA. γH2AX foci in iPSCs also colocalized to BRCA1 and RAD51, proteins in the homologous repair pathway, implying γH2AX in iPSCs marks sites of double strand breaks. [Stem Cells] Abstract Scientists demonstrated that C-terminal binding protein (Ctbp) isoform abundance was important for mouse embryonic ESCs (mESCs) to exit from pluripotency. Temporal expression patterns of Ctbp isoforms were quite different; Ctbp2 was more highly expressed in mESCs and decreased during differentiation, while Ctbp1 was constantly expressed at a lower level. Ctbp2 knockdown, but not Ctbp1 knockdown, in mESCs resulted in impaired exit from pluripotency. [FASEB J] Abstract Investigators reported strong variations in housekeeping gene stability during the reprogramming process. The most stable genes were Atp5f1, Pgk1 and Gapdh, while the least stable genes were Rps18, Hprt, Tbp and Actb. The results were validated by a proof-of-point quantitative polymerase chain reaction (qPCR) experiment with pluripotent markers Nanog, Rex1 and Oct4 normalized to the best and the worst reference gene identified by the analyses. [Sci Rep] Full Article iKA-CRISPR hESCs for Inducible and Multiplex Orthogonal Gene Knockout and Activation Researchers established human ESCs (hESCs) for inducible and multiplex orthogonal gene knockout and activation, which they named iKA-CRISPR hESCs. In cells, when complexed with a short guide RNA (gRNA) containing a 14-bp target sequence or a long 20bp-gRNA, the doxycycline-induced Cas9-p300 protein could activate gene transcription or cleave genomic DNA, respectively. [FEBS Lett] Abstract Scientists reported that cripto-1 protein produced by human ESC (hESC) represented a factor capable of inducing formation of supernumerary centrosomes in cultured hESC. Elimination of cripto-1 signaling on the other hand restored the normal number of centrosomes in hESC. [Stem Cells Dev] Abstract The authors found that FGF4 was required for neural induction, SB431542 accelerated neural precursor differentiation, and treatment with XAV939 and BIO at different periods enhanced neuronal differentiation. [Biochem Biophys Res Commun] Abstract Gas41 Links Histone Acetylation to H2A.Z Deposition and Maintenance of Embryonic Stem Cell Identity Investigators showed that glioma amplified sequence 41 (Gas41), a shared subunit of the two H2A.Z-depositing complexes, functioned as a reader of histone lysine acetylation and recruited Tip60/p400 and SRCAP to deposit H2A.Z into specific chromatin regions including bivalent domains. The YEATS domain of Gas41 bound to acetylated histone H3K27 and H3K14 both in vitro and in cells. [Cell Discov] Full Article | |
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REVIEWSHarnessing Cell Pluripotency for Cardiovascular Regenerative Medicine The authors discuss recent advances in cardiac-cell differentiation from human PSCs and in the direct reprogramming of non-myocyte cells for cardiovascular regenerative applications. They also discuss approaches for the delivery of cells to diseased tissue, and how such advances are contributing to progress in cardiac tissue engineering for tackling heart disease. [Nat Biomed Eng] Abstract Role of Human Oocyte-Enriched Factors in Somatic Cell Reprograming Researchers focus on studies identifying human oocyte-enriched factors aiming to understand the molecular mechanisms mediating cellular reprograming. They describe the role of oocyte-enriched factors in metabolic switch, chromatin remodelling, and global epigenetic transformation. [Mech Ageing Dev] Abstract Visit our reviews page to see a complete list of reviews in the ESC & iPSC research field. | |
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INDUSTRY NEWSAthersys Announces Expansion of Collaboration with Healios Under the terms of the agreements, Healios obtained exclusive licenses for the development and commercialization in Japan of MultiStem® therapy for the treatment of acute respiratory distress syndrome and of MultiStem cells used in combination with iPSC-derived cells for the treatment of certain organs. [Athersys Inc.] Press Release Orig3n Announces Osteoarthritis Cartilage Regeneration for First Cell Therapy Program Orig3n, announced its focus on osteoarthritis indications for its Cartilage Regeneration Program, the company’s first iPS-derived cell therapy program. [Orig3n (PR Newswire Association LLC.)] Press Release National Cancer Institute Selects ASU to Lead Revolutionary Research in Cancer Arizona State University (ASU) has been awarded more than $8.5 million over five years from the National Cancer Institute to establish the Arizona Cancer and Evolution Center. The grant will establish ASU as the hub of an international network of research scientists who are dedicated to understanding cancer in an entirely new way. [Arizona State University] Press Release | |
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POLICY NEWSHuman Embryo Research Policy Update In support of efforts by the International Society for Stem Cell Research (ISSCR) and other stakeholders to promote the ethical conduct of stem cell research, Nature journals have released an updated policy (https://www.nature.com/authors/policies/experimental.html). The policy, which formalizes and refines longstanding editorial practices, encourages scientists to adopt the ISSCR guidelines. [Nat Biotechnol] Editorial Sexual Harassment Is Rife in the Sciences, Finds Landmark US Study Sexual harassment is pervasive throughout academic science in the United States, driving talented researchers out of the field and harming others’ careers, finds a report from the US National Academies of Sciences, Engineering, and Medicine in Washington DC. The analysis concludes that policies to fight the problem are ineffective because they are set up to protect institutions, not victims — and that universities, funding agencies, scientific societies and other organizations must take stronger action. [Nature News] Editorial North American Universities Increasingly Cancel Publisher Packages Florida State University (FSU) will head into negotiations with the publisher Elsevier to see how it can resolve a pricing issue. Back in April, FSU announced that it would not renew a so-called “big deal” with Elsevier in 2019, due to its “high and ever-increasing cost,” and would instead subscribe to a subset of the most-needed journals. [The Scientist] Editorial Leading Salk Scientist Resigns after Allegations of Harassment The prominent cancer biologist Inder Verma unconditionally resigned from the Salk Institute for Biological Studies in San Diego, California, June 6, and the research institute’s board of trustees voted unanimously to accept his resignation. [ScienceInsider] Editorial China Introduces Sweeping Reforms to Crack Down on Academic Misconduct China is getting tough on scientific misconduct. The country’s most powerful bodies, the Chinese Communist Party and the State Council, introduced a raft of reforms on 30 May aimed at improving integrity across the research spectrum, from funding and job applications to peer-review and publications. [Nature News] Editorial More Restrictive U.S. Policy on Chinese Graduate Student Visas Raises Alarm Reversing yet another policy of the previous administration, the U.S. Department of State began applying tougher restrictions on some Chinese graduate students. The new policy shortens from five years to one year the duration of visas for those planning to study aviation, robotics, and advanced manufacturing. [ScienceInsider] Editorial
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EVENTSNEW The New York Stem Cell Foundation (NYSCF) Conference Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Research Associate/PhD Position – iPSCs & Neurodegenerative Disease (TU Dresden) NEW Research Specialist – Cardiovascular Disease (University of Illinois) Postdoctoral Research Associate – Embryonic Stem Cell Research (University of Illinois) Research Technologist – Pluripotent Stem Cell Biology (STEMCELL Technologies Inc.) Research Technologist – Stem Cell Biology (STEMCELL Technologies Inc.) Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.) Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.) Senior Scientist/ Scientist – Tissue Engineering (Novoheart) Postdoctoral Fellow – hiPSC Based Cardiac Regeneration (Duke University) Postdoctoral Fellow – Human Skeletal Muscle Disease Modeling and Regeneration (Duke University) PhD Candidate Position – Cardiovascular Diseases and iPSCs (University Medical Center Göttingen) Scientist/Senior Scientist – Bioprocess Engineering (Bluerock Therapeutics, LLC.) Postdoctoral Fellow – Cardiovascular Tissue Engineering (Stanford University) Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham) Postdoctoral Fellow – Stem Cells, Development and Cancer (Albert Einstein College of Medicine) Postdoctoral Associate – hiPSC-Based Brain Organoids (Rutgers University) Postdoctoral Fellow – Stem Cell Biology (City of Hope) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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