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Your search keyword '"Tischler, Julia"' showing total 3 results
Start Over Author "Tischler, Julia" Topic germ cells
3 results on '"Tischler, Julia"'

1. Metabolic regulation of pluripotency and germ cell fate through α-ketoglutarate.

Author

Tischler J, Gruhn WH, Reid J, Allgeyer E, Buettner F, Marr C, Theis F, Simons BD, Wernisch L, and Surani MA

Subjects
Animals, Cell Differentiation genetics, Cells, Cultured, Embryo, Mammalian, Embryonic Stem Cells physiology, Epigenesis, Genetic drug effects, Epigenesis, Genetic genetics, Female, Gene Expression Regulation, Developmental drug effects, Germ Cells physiology, Ketoglutaric Acids metabolism, Male, Metabolic Networks and Pathways drug effects, Metabolic Networks and Pathways genetics, Mice, Mice, Inbred C57BL, Mice, Transgenic, Pluripotent Stem Cells physiology, Cell Differentiation drug effects, Embryonic Stem Cells drug effects, Germ Cells drug effects, Ketoglutaric Acids pharmacology, Pluripotent Stem Cells drug effects
Abstract

An intricate link is becoming apparent between metabolism and cellular identities. Here, we explore the basis for such a link in an in vitro model for early mouse embryonic development: from naïve pluripotency to the specification of primordial germ cells (PGCs). Using single-cell RNA-seq with statistical modelling and modulation of energy metabolism, we demonstrate a functional role for oxidative mitochondrial metabolism in naïve pluripotency. We link mitochondrial tricarboxylic acid cycle activity to IDH2-mediated production of alpha-ketoglutarate and through it, the activity of key epigenetic regulators. Accordingly, this metabolite has a role in the maintenance of naïve pluripotency as well as in PGC differentiation, likely through preserving a particular histone methylation status underlying the transient state of developmental competence for the PGC fate. We reveal a link between energy metabolism and epigenetic control of cell state transitions during a developmental trajectory towards germ cell specification, and establish a paradigm for stabilizing fleeting cellular states through metabolic modulation., (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)

Published
2019
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2. Prdm14 promotes germline fate and naive pluripotency by repressing FGF signalling and DNA methylation.

Author

Grabole N, Tischler J, Hackett JA, Kim S, Tang F, Leitch HG, Magnúsdóttir E, and Surani MA

Subjects
Animals, Cell Differentiation, DNA Methylation, DNA-Binding Proteins, Embryonic Stem Cells cytology, Fibroblast Growth Factors metabolism, Gene Expression Profiling, Germ Cells cytology, Germ Layers cytology, Germ Layers metabolism, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mitogen-Activated Protein Kinases genetics, Mitogen-Activated Protein Kinases metabolism, Pluripotent Stem Cells cytology, RNA-Binding Proteins, Signal Transduction, Transcription Factors metabolism, Embryonic Stem Cells metabolism, Fibroblast Growth Factors genetics, Gene Expression Regulation, Developmental, Germ Cells metabolism, Pluripotent Stem Cells metabolism, Transcription Factors genetics
Abstract

Primordial germ cells (PGCs) and somatic cells originate from postimplantation epiblast cells in mice. As pluripotency is lost upon differentiation of somatic lineages, a naive epigenome and the pluripotency network are re-established during PGC development. Here we demonstrate that Prdm14 contributes not only to PGC specification, but also to naive pluripotency in embryonic stem (ES) cells by repressing the DNA methylation machinery and fibroblast growth factor (FGF) signalling. This indicates a critical role for Prdm14 in programming PGCs and promoting pluripotency in ES cells.

Published
2013
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3. Metabolic regulation of pluripotency and germ cell fate through α-ketoglutarate

Author

Tischler, Julia, Gruhn, Wolfram H, Reid, John, Allgeyer, Edward, Buettner, Florian, Marr, Carsten, Theis, Fabian, Simons, Ben D, Wernisch, Lorenz, Surani, M Azim, Tischler, Julia [0000-0003-4665-4141], Allgeyer, Edward [0000-0002-2187-4423], Buettner, Florian [0000-0001-5587-6761], Theis, Fabian [0000-0002-2419-1943], Surani, M Azim [0000-0002-8640-4318], and Apollo - University of Cambridge Repository

Subjects
Male, Pluripotent Stem Cells, germ cells, single‐cell analysis, Gene Expression Regulation, Developmental, Cell Differentiation, Mice, Transgenic, Embryo, Mammalian, Epigenesis, Genetic, Mice, Inbred C57BL, Mice, cell state transitions, Animals, Ketoglutaric Acids, Female, metabolism, pseudotime analysis, Cells, Cultured, Embryonic Stem Cells, Metabolic Networks and Pathways
Abstract

An intricate link is becoming apparent between metabolism and cellular identities. Here, we explore the basis for such a link in an in vitro model for early mouse embryonic development: from naïve pluripotency to the specification of primordial germ cells (PGCs). Using single-cell RNA-seq with statistical modelling and modulation of energy metabolism, we demonstrate a functional role for oxidative mitochondrial metabolism in naïve pluripotency. We link mitochondrial tricarboxylic acid cycle activity to IDH2-mediated production of alpha-ketoglutarate and through it, the activity of key epigenetic regulators. Accordingly, this metabolite has a role in the maintenance of naïve pluripotency as well as in PGC differentiation, likely through preserving a particular histone methylation status underlying the transient state of developmental competence for the PGC fate. We reveal a link between energy metabolism and epigenetic control of cell state transitions during a developmental trajectory towards germ cell specification, and establish a paradigm for stabilizing fleeting cellular states through metabolic modulation.

Published
2018
Full Text
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