ESC & iPSC News Volume 14.06 | Feb 20 2019

TOP STORY

Fine Tuning the Extracellular Environment Accelerates the Derivation of Kidney Organoids from Human Pluripotent Stem Cells

By lengthening the time that human PSCs were exposed to a 3D microenvironment, and by applying defined renal inductive signals, scientists generated kidney organoids that transcriptomically matched second-trimester human fetal kidneys. They validated these results using ex vivo and in vitro assays that modeled renal development. [Nat Mater] Abstract

(Ranked by impact factor of the journal)

Hypoimmunogenic Derivatives of Induced Pluripotent Stem Cells Evade Immune Rejection in Fully Immunocompetent Allogeneic Recipients

Investigators showed that both mouse and human iPSCs lost their immunogenicity when major histocompatibility complex class I and II genes were inactivated and CD47 was over-expressed. These hypoimmunogenic iPSCs retained their pluripotent stem cell potential and differentiation capacity. [Nat Biotechnol] Abstract | Press Release

Pluripotent Stem Cell-Derived Myogenic Progenitors Remodel Their Molecular Signature upon In Vivo Engraftment

Researchers showed that in vitro-generated PSC-derived myogenic progenitors possessed a molecular signature similar to embryonic/fetal myoblasts. However, compared with fetal myoblasts, following transplantation they showed superior myofiber engraftment and ability to seed the satellite cell niche, responded to multiple reinjuries, and contributed to long-term regeneration. [Proc Natl Acad Sci USA] Abstract | Press Release

Identifying Extrinsic versus Intrinsic Drivers of Variation in Cell Behavior in Human iPSC Lines from Healthy Donors

The authors integrated high content imaging of cell shape, proliferation, and other phenotypes with gene expression and DNA sequence datasets from over 100 human iPSC lines. They identified genes that correlated in expression with intrinsic and extrinsic probabilistic estimation of expression residuals factors and associated outlier cell behavior with genes containing rare deleterious non-synonymous SNVs. [Cell Rep] Full Article | Graphical Abstract

A Double Fail-Safe Approach to Prevent Tumorigenesis and Select Pancreatic β Cells from Human Embryonic Stem Cells

Scientists report the generation of a modified human ESC line harboring two suicide gene cassettes, whose expression resulted in cell death in the presence of specific pro-drugs. They showed the efficacy of this system at enriching for β cells and eliminating tumorigenic ones both in vitro and in vivo. [Stem Cell Reports] Full Article | Press Release | Graphical Abstract

Anti-Apoptotic Mutations Desensitize Human Pluripotent Stem Cells to Mitotic Stress and Enable Aneuploid Cell Survival

Human PSCs (hPSCs) expressed high levels of proapoptotic protein NOXA in undifferentiated state. Knocking out NOXA by CRISPR or upregulation of the anti-apoptosis gene BCL-XL significantly reduced mitotic cell death, allowing the survival of aneuploid cells and the formation of teratomas significantly larger than their wild-type parental hPSCs. [Stem Cell Reports] Full Article | Graphical Abstract

m⁶A Methylation Controls Pluripotency of Porcine Induced Pluripotent Stem Cells by Targeting SOCS3/JAK2/STAT3 Pathway in a YTHDF1/YTHDF2-Orchestrated Manner

Loss of METTL3 significantly impaired self-renewal and triggered differentiation of porcine iPSCs by interfering with JAK2 and SOCS3 expression, further inactivating the JAK2-STAT3 pathway, which then blocked the transcription of KLF4 and SOX2. [Cell Death Dis] Full Article

Allele-Specific RNA-Seq Expression Profiling of Imprinted Genes in Mouse Isogenic Pluripotent States

Global analysis showed that proper imprinted gene expression as observed in embryonic tissues was largely lost in the ESC lines, which mainly consisted of female ESCs. Differentiation of ESC lines to embryoid bodies or NPCs did not restore monoallelic expression of imprinted genes, neither did reprogramming of the serum-cultured ESCs to the pluripotent ground state by the use of two kinase inhibitors. [Epigenetics Chromatin] Full Article

Human Fibrinogen for Maintenance and Differentiation of Induced Pluripotent Stem Cells in Two Dimensions and Three Dimensions

iPSCs successfully adhered to and proliferated on fibrin hydrogels. The 2D culture with fibrinogen allowed for immediate adaption of culture models to a nonxenogeneic model. Similarly, multiple commercially available iPSC lines adhered to and proliferated on fibrinogen coated surfaces. iPSCs cultured on fibrinogen expressed similar levels of the pluripotent stem cell markers SSea4, Oct3/4, TRA1-60, and NANOG compared with iPSCs on Geltrex. [Stem Cells Transl Med] Full Article

MicroRNA-690 Regulates Induced Pluripotent Stem Cells (iPSCs) Differentiation into Insulin-Producing Cells by Targeting Sox9

Quantitative Real-Time PCR, Western blotting, and immunostaining assays were performed to examine the pancreatic function of insulin-producing cells (IPCs) at mRNA and protein level respectively. Flow cytometry and ELISA were performed to detect differentiation efficiency and insulin content and secretion from iPSCs-derived IPCs in response to stimulation at different concentration of glucose. [Stem Cell Res Ther] Full Article

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Personalized Medicine in Cardio-Oncology: The Role of iPSC

With the advent of human iPSC technology, researchers not only have the opportunity to model human diseases, but also to screen drugs for their efficacy and toxicity using human cell models. In this review, the authors discuss the role of iPSCs in modeling chemotherapy-induced cardiotoxicity. [Cardiovasc Res] Abstract

Visit our reviews page to see a complete list of reviews in the ESC & iPSC research field.

StemoniX^® Uses microBrain^® 3D, a Functional In Vitro Human Neural Model, to Identify Potential Treatment Modalities for Rett Syndrome

StemoniX^® Inc. announced that Cassiano Carromeu, PhD, lead neuroscientist at StemoniX, presented research during the SLAS2019 annual meeting demonstrating the ability of microBrain^® 3D to produce a functional in vitro disease model for Rett Syndrome (RTT) via human iPSCs derived from RTT patients. [Press release from StemoniX^® Inc. discussing research presented at SLAS2019, Washington, DC] Press Release

Keio to Begin World First iPS Clinical Trial for Spinal Injuries

The Subcommittee for Regenerative Medicine of the Health Sciences Council of the Ministry of Health, Labor and Welfare has given conditional approval to a plan submitted by Keio University Hospital for clinical research on the use of iPS cells to treat spinal cord injuries. The Keio University team will be led by Professor Hideyuki Okano, of the Department of Physiology, and Professor Masaya Nakamura, of the Department of Orthopedic Surgery, at the Keio University School of Medicine. [Keio University] Press Release

Announcing the 2019 Sloan Research Fellows

The Alfred P. Sloan Foundation announced the selection of 126 outstanding US and Canadian researchers as the recipients of the 2019 Sloan Research Fellowships. The fellowships, awarded yearly since 1955, honor early-career scholars whose achievements mark them as among the most promising researchers in their fields. [The Alfred P. Sloan Foundation] Press Release

Facebook’s Controversies Now Extend to Health and Medicine Issues

The Facebook controversies have come to the world of health and medicine. After last year’s scandals involving Cambridge Analytica and Russian trolls, this time the controversies concern anti-vaccine information and health privacy. [STAT News] Editorial

Trump Science Adviser Calls for More Collaboration Between Industry and Government

Kelvin Droegemeier, newly minted science adviser to US President Donald Trump, wants industry to take a larger role in funding research, with the ultimate goal of ushering in a “second golden era” of US science. [Nature News] Editorial

Scientists Raise Concerns About Revisions to Human Research Regulations

Authors of a new paper take issue with revisions to regulations on biospecimen research enacted last month, and argue that cell lines should be treated differently from other biospecimens. [The Scientist] Editorial

NEW ISCT 2019 Annual Scientific Meeting
May 29-June 1, 2019
Melbourne, Australia

NEW Keystone Symposia: Cancer Stem Cells – Advances in Biology and Clinical Translation
October 13-17, 2019
Hong Kong, China

Visit our events page to see a complete list of events in the community.

NEW Research Scientist – iPSC-Based Products (Life & Brain GMBH)

Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Scientist – Cell Culture Media and Cell Line Development (STEMCELL Technologies Inc.)

Postdoctoral Scholarship – Glioblastoma Stem Cell Research (Lund University)

PhD Position – Stem Cell Research (Luxembourg Institute of Health)

Postdoctoral Position – Stem Cell Science and Genome Editing (Max Delbrück Center For Molecular Medicine)

Postdoctoral Research Fellow – Discovery Oncology (Merck)

Postdoctoral Position – Stem Cells & Neurodegeneration (Lund University)

Postdoctoral Fellow – Stem Cell Biology (City of Hope)

Postdoctoral Fellow – Genetics and Epigenomics of iPSC Biology (Stanford University)

Assistant Associate Professor/Professor in Residence – Stem Cell Program (UC Davis)

Assistant/Associate Adjunct Professor – Cardiovascular Medicine (UC Davis)

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