18 results found
Azuara V, Mau KHT, Karimlou D, et al., 2022, Dynamic enlargement and mobilization of lipid droplets in pluripotent cells coordinate morphogenesis during mouse peri-implantation development, Nature Communications, Vol: 13, ISSN: 2041-1723
Mammalian pre-implantation embryos accumulate substantial lipids, which are stored in lipid droplets (LDs). Despite the fundamental roles of lipids in many cellular functions, the significance of building-up LDs for the developing embryo remains unclear. Here we report that the accumulation and mobilization of LDs upon implantation are causal in the morphogenesis of the pluripotent epiblast and generation of the pro-amniotic cavity in mouse embryos, a critical step for all subsequent development. We show that the CIDEA protein, found abundantly in adipocytes, enhances lipid storage in blastocysts and pluripotent stem cells by promoting LD enlargement through fusion. The LD-stored lipids are mobilized into lysosomes at the onset of lumenogenesis, but without CIDEA are prematurely degraded by cytosolic lipases. Loss of lipid storage or inactivation of lipophagy leads to the aberrant formation of multiple cavities within disorganised epithelial structures. Thus, our study reveals an unexpected role for LDs in orchestrating tissue remodelling and uncovers underappreciated facets of lipid metabolism in peri-implantation development.
Xie SQ, Leeke BJ, Whidling C, et al., 2021, Nucleolar-based <i>Dux</i> repression is essential for 2-cell stage exit
<jats:title>Abstract</jats:title><jats:p>Upon fertilisation, the mammalian embryo must switch from dependence on maternal transcripts to transcribing its own genome, and in mice involves the transient upregulation of MERVL transposons and MERVL-driven genes at the 2-cell stage. The mechanisms and requirement for MERVL and 2-cell (2C) gene upregulation are poorly understood. Moreover, this MERVL-driven transcriptional program must be rapidly shut off to allow 2C exit and developmental progression. Here, we report that robust ribosomal RNA (rRNA) synthesis and nucleolar maturation are essential for exit from the 2C state. 2C-like cells and 2C embryos show similar immature nucleoli with altered structure and reduced rRNA output. We reveal that nucleolar disruption via blocking Pol I activity or preventing nucleolar phase separation enhances conversion to a 2C-like state in embryonic stem cells (ESCs) by detachment of the MERVL activator <jats:italic>Dux</jats:italic> from the nucleolar surface. In embryos, nucleolar disruption prevents proper <jats:italic>Dux</jats:italic> silencing and leads to 2-4 cell arrest. Our findings reveal an intriguing link between rRNA synthesis, nucleolar maturation and gene repression during early development.</jats:p>
Percharde M, Lin C-J, Ramalho-Santos M, 2021, Depletion of nuclear LINE1 RNA in mouse ESCs and embryos., STAR Protoc, Vol: 2
LINE1 is the most active and abundant family of retrotransposons; it is implicated in a number of pathologies, as well as in early embryo development. We present a protocol to specifically knockdown LINE1 in mouse embryonic stem cells and embryos, including details for the nucleofection and zygote microinjection of LINE antisense oligos, followed by RNA FISH validation. This protocol can be used in development, as well as other cell types where LINE1 is believed to be expressed. For complete information on the use and execution of this protocol, please refer to Percharde et al. (2018).
Lu JY, Chang L, Li T, et al., 2021, Homotypic clustering of L1 and B1/Alu repeats compartmentalizes the 3D genome, CELL RESEARCH, Vol: 31, Pages: 613-630, ISSN: 1001-0602
Kuwahara A, Lewis AE, Coombes C, et al., 2020, Delineating the early transcriptional specification of the mammalian trachea and esophagus, ELIFE, Vol: 9, ISSN: 2050-084X
Lu JY, Shao W, Chang L, et al., 2020, Genomic Repeats Categorize Genes with Distinct Functions for Orchestrated Regulation, CELL REPORTS, Vol: 30, Pages: 3296-+, ISSN: 2211-1247
Percharde M, Sultana T, Ramalho-Santos M, 2020, What Doesn't Kill You Makes You Stronger: Transposons as Dual Players in Chromatin Regulation and Genomic Variation, BIOESSAYS, Vol: 42, ISSN: 0265-9247
Lu JY, Chang L, Li T, et al., 2019, L1 and B1 repeats blueprint the spatial organization of chromatin
<jats:title>SUMMARY</jats:title><jats:p>Despite extensive mapping of three-dimensional (3D) chromatin structures, the basic principles underlying genome folding remain unknown. Here, we report a fundamental role for L1 and B1 retrotransposons in shaping the macroscopic 3D genome structure. Homotypic clustering of B1 and L1 repeats in the nuclear interior or at the nuclear and nucleolar peripheries, respectively, segregates the genome into mutually exclusive nuclear compartments. This spatial segregation of L1 and B1 is conserved in mouse and human cells, and occurs dynamically during establishment of the 3D chromatin structure in early embryogenesis and the cell cycle. Depletion of L1 transcripts drastically disrupts the spatial distributions of L1- and B1-rich compartments. L1 transcripts are strongly associated with L1 DNA sequences and induce phase separation of the heterochromatin protein HP1α. Our results suggest that genomic repeats act as the blueprint of chromatin macrostructure, thus explaining the conserved higher-order structure of chromatin across mammalian cells.</jats:p>
DiTroia SP, Percharde M, Guerquin M-J, et al., 2019, Maternal vitamin C regulates reprogramming of DNA methylation and germline development, NATURE, Vol: 573, Pages: 271-+, ISSN: 0028-0836
Percharde M, Lin C-J, Yin Y, et al., 2018, A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity, CELL, Vol: 174, Pages: 391-+, ISSN: 0092-8674
Bulut-Karslioglu A, Macrae TA, Oses-Prieto JA, et al., 2018, The Transcriptionally Permissive Chromatin State of Embryonic Stem Cells Is Acutely Tuned to Translational Output, CELL STEM CELL, Vol: 22, Pages: 369-+, ISSN: 1934-5909
Bulut-Karslioglu A, Macrae TA, Oses-Prieto JA, et al., 2017, The transcriptionally permissive chromatin state of ES cells is acutely tuned to translational output
<jats:title>SUMMARY</jats:title><jats:p>A permissive chromatin environment coupled to hypertranscription is critical to drive the rapid proliferation of Embryonic Stem (ES) cells and peri-implantation embryos. We carried out a genome-wide screen to systematically dissect the regulation of the euchromatic state of ES cells. The results reveal that activity of cellular growth pathways, prominently protein synthesis, perpetuates the euchromatic state and hypertranscription of ES cells. Acute, mild inhibition of translation results in rapid depletion of euchromatic marks in ES cells and blastocysts, concurrent with delocalization of RNA polymerase II and reduction in nascent transcription. Remarkably, reduced translational output leads to rewiring of open chromatin within 3 hours, including decreased accessibility at a subset of active developmental enhancers and increased accessibility at histone genes and transposable elements. Using a proteome-scale analysis, we show that several euchromatin regulators are unstable proteins and thus continuously depend on a high translational output. We propose that this mechanistic interdependence of euchromatin, transcription and translation sets the pace of proliferation at peri-implantation and may be employed generally by stem/progenitor cells.</jats:p>
Percharde M, Wong P, Ramalho-Santos M, 2017, Global Hypertranscription in the Mouse Embryonic Germline, CELL REPORTS, Vol: 19, Pages: 1987-1996, ISSN: 2211-1247
Percharde M, Bulut-Karslioglu A, Ramalho-Santos M, 2017, Hypertranscription in Development, Stem Cells, and Regeneration, DEVELOPMENTAL CELL, Vol: 40, Pages: 9-21, ISSN: 1534-5807
Percharde M, Azuara V, 2013, Essential roles for the nuclear receptor coactivator Ncoa3 in pluripotency, CELL CYCLE, Vol: 12, Pages: 195-196, ISSN: 1538-4101
Percharde M, Lavial F, Ng J-H, et al., 2012, Ncoa3 functions as an essential Esrrb coactivator to sustain embryonic stem cell self-renewal and reprogramming, GENES & DEVELOPMENT, Vol: 26, Pages: 2286-2298, ISSN: 0890-9369
Lopez J, Percharde M, Coley HM, et al., 2009, The context and potential of epigenetics in oncology, BRITISH JOURNAL OF CANCER, Vol: 100, Pages: 571-577, ISSN: 0007-0920
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.