Journal ArticleDOI
Safeguards for Cell Cooperation in Mouse Embryogenesis Shown by Genome-Wide Cheater Screen
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TLDR
Using a genome-wide screen in murine induced pluripotent stem cells, a network of genes was identified whose down-regulation caused the cells to replace wild-type cells in vitro and in the mouse embryo—without perturbing normal development.Abstract:
Ensuring cooperation among formerly autonomous cells has been a central challenge in the evolution of multicellular organisms. One solution is monoclonality, but this option still leaves room for exploitative behavior, as it does not eliminate genetic and epigenetic variability. We therefore hypothesized that embryonic development must be protected by robust regulatory mechanisms that prevent aberrant clones from superseding wild-type cells. Using a genome-wide screen in murine induced pluripotent stem cells, we identified a network of genes (centered on p53, topoisomerase 1, and olfactory receptors) whose down-regulation caused the cells to replace wild-type cells in vitro and in the mouse embryo--without perturbing normal development. These genes thus appear to fulfill an unexpected role in fostering cell cooperation.read more
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Journal ArticleDOI
Putting p53 in Context
TL;DR: TP53 is the most frequently mutated gene in human cancer and must be interpreted to understand how cell type, mutation profile, and epigenetic cell state dictate outcomes, and how might it restore its tumor-suppressive activities in cancer.
Journal ArticleDOI
PPM1D Mutations Drive Clonal Hematopoiesis in Response to Cytotoxic Chemotherapy.
Joanne I. Hsu,Joanne I. Hsu,Tajhal Dayaram,Ayala Tovy,Etienne De Braekeleer,Etienne De Braekeleer,Mira Jeong,Feng Wang,Jianhua Zhang,Timothy P. Heffernan,Sonal Gera,Jeffrey J. Kovacs,Joseph R. Marszalek,Christopher A. Bristow,Yuanqing Yan,Guillermo Garcia-Manero,Hagop M. Kantarjian,George S. Vassiliou,George S. Vassiliou,P. Andrew Futreal,Lawrence A. Donehower,Koichi Takahashi,Margaret A. Goodell,Margaret A. Goodell +23 more
TL;DR: It is found that mutations in PPM1D (protein phosphatase Mn2+/Mg2+-dependent 1D), a DNA damage response regulator that is frequently mutated in CH, were present in one-fifth of patients with therapy-related acute myeloid leukemia or myelodysplastic syndrome and strongly correlated with cisplatin exposure.
Journal ArticleDOI
The histone chaperone CAF-1 safeguards somatic cell identity
Sihem Cheloufi,Sihem Cheloufi,Ulrich Elling,Barbara Hopfgartner,Youngsook L. Jung,Youngsook L. Jung,Jernej Murn,Jernej Murn,Maria Ninova,Maria Hubmann,Aimee I. Badeaux,Aimee I. Badeaux,Cheen Euong Ang,Danielle Tenen,Danielle Tenen,Daniel J. Wesche,Daniel J. Wesche,Nadezhda Abazova,Nadezhda Abazova,Max Hogue,Max Hogue,Nilgun Tasdemir,Justin Brumbaugh,Justin Brumbaugh,Philipp Rathert,Julian Jude,Francesco Ferrari,Francesco Ferrari,Andres Blanco,Andres Blanco,Michaela Fellner,Daniel Wenzel,Marietta Zinner,Simon E. Vidal,Oliver Bell,Matthias Stadtfeld,Howard Y. Chang,Howard Y. Chang,Geneviève Almouzni,Scott W. Lowe,Scott W. Lowe,John L. Rinn,John L. Rinn,Marius Wernig,Alexei A. Aravin,Yang Shi,Yang Shi,Peter J. Park,Peter J. Park,Josef M. Penninger,Johannes Zuber,Konrad Hochedlinger,Konrad Hochedlinger +52 more
TL;DR: The findings reveal the histone chaperone CAF-1 to be a novel regulator of somatic cell identity during transcription-factor-induced cell-fate transitions and provide a potential strategy to modulate cellular plasticity in a regenerative setting.
Journal ArticleDOI
Rethinking Differentiation: Stem Cells, Regeneration, and Plasticity
TL;DR: Past and recent discoveries in plants and animals, as well as novel experimental manipulations, are beginning to erode many of these established concepts and are forcing a re-evaluation of the experimental systems and paradigms presently being used to explore these and other biological process.
Journal ArticleDOI
Cell competition: how to eliminate your neighbours.
Marc Amoyel,Erika A. Bach +1 more
TL;DR: Recent advances in the field as well as the mechanistic steps involved in this phenomenon have shed light on how and why cell competition exists in developing and adult organisms.
References
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Journal ArticleDOI
Analysis of relative gene expression data using real-time quantitative pcr and the 2(-delta delta c(t)) method
TL;DR: The 2-Delta Delta C(T) method as mentioned in this paper was proposed to analyze the relative changes in gene expression from real-time quantitative PCR experiments, and it has been shown to be useful in the analysis of realtime, quantitative PCR data.
Journal ArticleDOI
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.
TL;DR: Induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions is demonstrated and iPS cells, designated iPS, exhibit the morphology and growth properties of ES cells and express ES cell marker genes.
Journal ArticleDOI
Establishment in culture of pluripotential cells from mouse embryos
TL;DR: The establishment in tissue culture of pluripotent cell lines which have been isolated directly from in vitro cultures of mouse blastocysts are reported, able to differentiate either in vitro or after innoculation into a mouse as a tumour in vivo.
Book
Manipulating the mouse embryo: A laboratory manual
TL;DR: Here are recorded the tech- niques for preparing, inserting and analysing DNA sequences, for retroviral infection of mice, for production and use of EC and EK cells as vehicles for engineered sequences and for nuclear transplantation - all against a background of the basic procedures required for pro- ducing and handling the em- bryos.
Journal ArticleDOI
Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells
TL;DR: In this article, the authors described the establishment directly from normal preimplantation mouse embryos of a cell line that forms teratocarcinomas when injected into mice and demonstrated the pluripotency of these embryonic stem cells by the observation that subclonal cultures, derived from isolated single cells, can differentiate into a wide variety of cell types.
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