Low-input lipidomics reveals lipid metabolism remodelling during early mammalian embryo development

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(2), P. 278 - 293

Published: Feb. 1, 2024

Language: Английский

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Lumen expansion is initially driven by apical actin polymerization followed by osmotic pressure in a human epiblast model

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(5), P. 640 - 656.e8

Published: May 1, 2024

Language: Английский

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The transcription factor GABPA is a master regulator of naive pluripotency

Nature Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Abstract The establishment of naive pluripotency is a continuous process starting with the generation inner cell mass (ICM) that then differentiates into epiblast (EPI). Recent studies have revealed key transcription factors (TFs) for ICM formation, but which TFs initiate EPI specification remains unknown. Here, using targeted rapid protein degradation system, we show GABPA not only regulator major ZGA, also master specifier required by regulating 47% genes during E3.5 to E4.5 transition. Chromatin binding dynamics analysis suggests controls formation at least partly gene promoters occupied regulators TFAP2C and SOX2 establish E4.5. Our study uncovers as regulator, supports notion mammalian requires dynamic stepwise multi-TF regulatory network.

Language: Английский

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Transcriptome profiles of human preimplantation blastocysts related to mosaicism, developmental speed and competence

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(2)

Published: Jan. 24, 2025

Dear Editor, By taking advantage of parallel sequencing genome and transcriptome (G&T-seq),1 we demonstrated the distinct profiles human preimplantation blastocysts in perspectives embryo digital karyotype, developmental speed implantation competence. Our study provided valuable information for further research physiology behind development laid foundation selection from view transcriptome. Preimplantation genetic test aneuploidy (PGT-A) serves as an important invasive method to select euploid embryos. However, even PGT-A cannot guarantee a successful pregnancy,2 almost 50% could not result live birth. It means that there is still big room improve capability besides screening. RNA might have potential assessing competence.3, 4 Here investigated pre-implantation with application G&T-seq (Figure 1A). We verified this biopsied samples 41 donated terms consistency same blastocyst, prediction value aneuploidies by S1), well lineage characteristic inner cell mass (ICM) trophectoderm (TE) S2), indicating clinical safety reproducibility method. unique technology studying chromosomal mosaicism, separate sequencing. In comparisons transcriptomes 28 TE few-cell eight mosaic embryos 17 five euploidies 1B), identified 79 genes upregulated 37 downregulated 1C). Notably, ectoderm primitive endoderm genes, including KLF4, TGFBR1, ITGB5 GATA6, were significantly 1D). Furthermore, mainly enriched embryonic development, stem proliferation, other pathways (Table implying be separation disorder cells inadequately developed trophoblast may contribute adverse pregnancy outcomes Human different speeds. take 5–7 days develop grade stage according Gardner grading system, which allowing biopsy. Clinically, on day 6 or 7 (named D6 D7 blastocyst) are defined growth-retarded lower compared 5 blastocysts. The reason retarded remains clarified. To investigate related blastocyst potential, collected prospectively 105 couples who underwent PGT our reproductive centre 2A Table S2). Totally, 143 (D5 n = 82, 54 7) confirmed G&T-seq, detection efficiency screening was similar conventional NGS period S3). Transcriptionally, these obviously clustered 2B). seemed differentiated more maturely than D5 blastocysts, number expressed average levels marker genes5 S4) increased 6/7 2C,D). look at transcriptional changes normally 5th 7th after fertilization, nine cultured one two days, then sequentially treated form few-cells samples, named D5_D6 D5_D7 samples. characteristics totally but 2E). pseudotime trajectory nearly coincident respectively, roughly arranged fertilization 2F,G). Genes higher expression regulation mitochondrial membrane autophagy, population maintenance, while later (D6/7) amino acid metabolic protein biogenesis process, differentiation, canonical Wnt signalling pathway, placenta steroid biosynthetic process cadherin binding cell-cell adhesion 2H Figure Similar indicate differentiate autonomously clock tick depending morphology This novel finding least partly explain low point cross-talk between endometrium, since they transferred uterus window blastocysts.6, On hand, differentially (DEGs) grow-retarded D6/7 D5_D6/D5_D7 up-regulated DEGs GO regard establishment maintenance polarity S4), most events during early divisions.8 findings delayed-growing dysfunction polarity, consistent publication Wang et al., suggesting arrest share some common mechanism.9 factors affecting originated earlier embryological events, analysis time-lapse imaging shed light issues. Finally, pregnant non-pregnant baseline comparable groups, except ratio corresponding ICM S5). No significant clusters found, overall quite 3A). There DEGs, SOX4, TMSB4X, IFNAR1, C3orf14 CISD2, LRRC4, HTT HES4 group (adjusted p < .05, 3B,C). Moreover, established logistic regression model predicting combining markers characteristics. With use binary analysis, integrated patients' age, endometrial preparation protocol transfer cycle, morphological grade, transferred, highlighted mentioned above. Results revealed HTT, correlated young females S6). verify reported al.,3 due larger sample size good prognosis patients study. conclusion, evaluated transcriptome-wide approach competence found aberrant provide Yanwen Xu Canquan Zhou contributed design work. Song Li, Bing Cai, Chenhui Ding Muhua Lai performed experiments. Jialiu Liu Yan conducted data analysis. Li wrote first draft, revised manuscript. All authors editing reviewing final version supported National Key Research Development Program China (No. 2023YFC2705503 2018YFC1003102), Natural Science Foundation 82071716 81771588) Guangdong Province 201804020087). declare no conflict interest. approved Clinical Laboratory Animal Ethics Committee First Affiliated Hospital Sun Yat-sen University [2020]110), all informed consent. Please note: publisher responsible content functionality any supporting supplied authors. Any queries (other missing content) should directed author article.

Language: Английский

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Topological interactions drive the first fate decision in the Drosophila embryo

Nature Physics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Language: Английский

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The nuclear lamina couples mechanical forces to cell fate in the preimplantation embryo via actin organization

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 29, 2023

Abstract During preimplantation development, contractile forces generated at the apical cortex segregate cells into inner and outer positions of embryo, establishing cell mass (ICM) trophectoderm. To which extent these influence ICM-trophectoderm fate remains unresolved. Here, we found that nuclear lamina is coupled to via an F-actin meshwork in mouse human embryos. Actomyosin contractility increases during upregulating Lamin-A levels, but upon internalization lose their downregulate Lamin-A. Low shifts localization actin nucleators from nucleus cytoplasm increasing cytoplasmic abundance. This results stabilization Amot, Yap phosphorylation acquisition ICM over trophectoderm fate. By contrast, cells, levels increase with contractility. prevents enabling Cdx2 specify Thus, transmitted control organization differentially regulate factors specifying lineage identity.

Language: Английский

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Engineering programmable material-to-cell pathways via synthetic notch receptors to spatially control differentiation in multicellular constructs

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 13, 2024

Synthetic Notch (synNotch) receptors are genetically encoded, modular synthetic that enable mammalian cells to detect environmental signals and respond by activating user-prescribed transcriptional programs. Although some materials have been modified present synNotch ligands with coarse spatial control, applications in tissue engineering generally require extracellular matrix (ECM)-derived scaffolds and/or finer positioning of multiple ligands. Thus, we develop here a suite activate for generalizable material-to-cell signaling. We chemically fuse functional ECM proteins ECM-derived materials. also generate tissues microscale precision over four distinct reporter phenotypes culturing two orthogonal programs on surfaces microcontact-printed Finally, showcase co-transdifferentiating fibroblasts into skeletal muscle or endothelial cell precursors user-defined micropatterns. These technologies provide avenues spatially controlling cellular tissues.

Language: Английский

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A monoastral mitotic spindle determines lineage fate and position in the mouse embryo

Nature Cell Biology, Journal Year: 2022, Volume and Issue: 24(2), P. 155 - 167

Published: Jan. 31, 2022

Language: Английский

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Appreciating the role of cell shape changes in the mechanobiology of epithelial tissues

Biophysics Reviews, Journal Year: 2022, Volume and Issue: 3(1)

Published: March 1, 2022

The wide range of epithelial cell shapes reveals the complexity and diversity intracellular mechanisms that serve to construct their morphology regulate functions. Using mechanosensitive steps, cells can sense a variety different mechanochemical stimuli adapt behavior by reshaping morphology. These changes shape rely on structural reorganization in space time generates modifications tensional state activates biochemical cascades. Recent studies have started unveil how maintenance is involved mechanical homeostatic tasks sustain tissue folding, identity, self-renewal. Here, we review relevant works integrated mechanobiology elucidate some core principles may be conveyed into spatial information guide collective processes such as morphogenesis. Among many other parameters, show regulation understood result interplay between two counteracting mechanisms: actomyosin contractility intercellular adhesions, both do not act independently but are functionally operate molecular, cellular, scales. We highlight role cadherin-based adhesions force-sensing mechanotransduction, report recent developments exploit physics liquid crystals connect orientational order aggregates. Finally, emphasize further intermingling disciplines develop new assays will lead way toward unified picture contribution pathophysiological tissues.

Language: Английский

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A Hierarchical Mechanotransduction System: From Macro to Micro

Advanced Science, Journal Year: 2023, Volume and Issue: 11(11)

Published: Dec. 25, 2023

Mechanotransduction is a strictly regulated process whereby mechanical stimuli, including forces and properties, are sensed translated into biochemical signals. Increasing data demonstrate that mechanotransduction crucial for regulating macroscopic microscopic dynamics functionalities. However, the actions mechanisms of across multiple hierarchies, from molecules, subcellular structures, cells, tissues/organs, to whole-body level, have not been yet comprehensively documented. Herein, biological roles operational macro micro revisited, with focus on orchestrations diverse hierarchies. The implications, applications, challenges in human diseases also summarized discussed. Together, this knowledge hierarchical perspective has potential refresh insights regulation disease pathogenesis therapy, ultimately revolutionize prevention, diagnosis, treatment diseases.

Language: Английский

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