Branching topology of the human embryo transcriptome revealed by entropy sort feature weighting DOI Creative Commons
Arthur Radley, Austin Smith

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 16, 2023

ABSTRACT Single cell transcriptomics (scRNA-seq) transforms our capacity to define states and reveal developmental trajectories. Resolution is challenged, however, by high dimensionality noisy data. Analysis therefore typically performed after sub-setting highly variable genes (HVGs). However, existing HVG selection techniques have been found poor agreement with one another, tend be biased towards expressed genes. Entropy sorting provides an alternative mathematical framework for feature subset selection. Here we implement continuous entropy sort weighting (cESFW). On synthetic datasets, cESFW outperforms in distinguishing state specific We apply six merged scRNA-seq datasets spanning human early embryo development. Without smoothing or augmenting the raw counts matrices, generates a high-resolution embedding displaying coherent progression from 8-cell post-implantation stages, delineating 15 distinct states. The highlights sequential lineage decisions during blastocyst development while unsupervised clustering identifies branch point populations. Cells previously claimed lack trajectory reside first branching region where morula differentiates into Inner Cell Mass (ICM) Trophectoderm (TE). quantify relatedness of pluripotent stem cultures types identify naïve primed marker conserved across culture conditions embryo. Finally, identifying specifically enriched dynamic expression formation, provide markers staging blastocyst. Together these analyses indicate that ability gene dynamics data can fail elucidate.

Language: Английский

The Dynamics of Histone Modifications during Mammalian Zygotic Genome Activation DOI Open Access
Francisco Sotomayor Lugo, Nataly Iglesias-Barrameda, Yandy Marx Castillo‐Aleman

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1459 - 1459

Published: Jan. 25, 2024

Mammalian fertilization initiates the reprogramming of oocytes and sperm, forming a totipotent zygote. During this intricate process, zygotic genome undergoes maternal-to-zygotic transition (MZT) subsequent activation (ZGA), marking initiation transcriptional control gene expression post-fertilization. Histone modifications are pivotal in shaping cellular identity many mammals. Recent advances chromatin analysis have enabled detailed explorations histone during ZGA. This review delves into conserved unique regulatory strategies, providing essential insights dynamic changes their variants ZGA The objective is to explore recent advancements leading mechanisms related governing embryonic development phase depth. These considerations will be useful for informing future therapeutic approaches that target epigenetic regulation diverse biological contexts. It also contribute extensive areas evolutionary developmental biology possibly lay foundation research discussion on seminal topic.

Language: Английский

Citations

16
Suppression of ERK signalling promotes pluripotent epiblast in the human blastocyst DOI Creative Commons
Claire Simon,

Afshan McCarthy,

Laura Woods

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 4, 2024

Abstract Studies in the mouse demonstrate importance of fibroblast growth factor (FGF) and extra-cellular receptor tyrosine kinase (ERK) specification embryo-fated epiblast yolk-sac-fated hypoblast cells from uncommitted inner cell mass (ICM) prior to implantation. Molecular mechanisms regulating early lineages human development are comparatively unclear. Here we show that exogenous FGF stimulation leads expanded molecular marker expression, at expense epiblast. Conversely, specifically inhibiting ERK activity expansion functionally capable giving rise naïve pluripotent stem cells. Single-cell transcriptomic analysis indicates these downregulate signalling upregulate markers associated with pluripotency. Our functional study demonstrates for first time governing ICM development, whereby segregation occurs during maturation mammalian embryo an signal-dependent manner.

Language: Английский

Citations

7
A single-cell transcriptome atlas of human euploid and aneuploid blastocysts DOI
Shengpeng Wang,

Lizhi Leng,

Quanlei Wang

et al.

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(7), P. 1468 - 1481

Published: June 5, 2024

Language: Английский

Citations

7
Pathology and Therapeutic Significance of Fibroblast Growth Factors DOI Open Access

Oshadi Edirisinghe,

Gaëtane Ternier,

Thallapuranam Krishnaswamy Suresh Kumar

et al.

Targets, Journal Year: 2025, Volume and Issue: 3(1), P. 5 - 5

Published: Feb. 2, 2025

The fibroblast growth factor (FGF) family includes 22 proteins in humans. Based on their mode of action, there are three families FGFs: paracrine FGFs (FGF 1–10, 16, 17, 18, 20, and 22), intracrine 11–14), endocrine 19, 21, 23). FGF signaling plays critical roles embryonic development, tissue repair, regeneration, angiogenesis, metabolic regulation. They exert cellular functions by binding, dimerization, activation transmembrane receptors (FGFRs). Aberrant is associated with various human diseases. Thus, understanding the unique properties will help to explore new therapeutic interventions against FGF-mediated pathological conditions. This review discuss differential expression regulation each under normal physiological Moreover, we outline current therapeutics treatment strategies that have been developed FGF-related pathology.

Language: Английский

Citations

1
Unlocking trophectoderm mysteries: In vivo and in vitro perspectives on human and mouse trophoblast fate induction DOI

Meir Azagury,

Yosef Buganim

Developmental Cell, Journal Year: 2024, Volume and Issue: 59(8), P. 941 - 960

Published: April 1, 2024

Language: Английский

Citations

6
Branching topology of the human embryo transcriptome revealed by Entropy Sort Feature Weighting DOI Creative Commons
Arthur Radley, Stefan Boeing, Austin Smith

et al.

Development, Journal Year: 2024, Volume and Issue: 151(11)

Published: May 1, 2024

Analysis of single cell transcriptomics (scRNA-seq) data is typically performed after subsetting to highly variable genes (HVGs). Here, we show that Entropy Sorting provides an alternative mathematical framework for feature selection. On synthetic datasets, continuous Sort Feature Weighting (cESFW) outperforms HVG selection in distinguishing cell-state-specific genes. We apply cESFW six merged scRNA-seq datasets spanning human early embryo development. Without smoothing or augmenting the raw counts matrices, generates a high-resolution embedding displaying coherent developmental progression from eight-cell post-implantation stages and delineating 15 distinct states. The highlights sequential lineage decisions during blastocyst development, while unsupervised clustering identifies branch point populations obscured previous analyses. first branching region, where morula cells become specified inner mass trophectoderm, includes previously asserted lack trajectory. quantify relatedness different pluripotent stem cultures types identify marker naïve primed pluripotency. Finally, by revealing with dynamic lineage-specific expression, provide markers staging blastocyst.

Language: Английский

Citations

4
Decoding FGF/FGFR Signaling: Insights into Biological Functions and Disease Relevance DOI Creative Commons

Oshadi Edirisinghe,

Gaëtane Ternier,

Zeina Alraawi

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(12), P. 1622 - 1622

Published: Dec. 18, 2024

Fibroblast Growth Factors (FGFs) and their cognate receptors, FGFRs, play pivotal roles in a plethora of biological processes, including cell proliferation, differentiation, tissue repair, metabolic homeostasis. This review provides comprehensive overview FGF-FGFR signaling pathways while highlighting complex regulatory mechanisms interconnections with other networks. Further, we briefly discuss the FGFs involvement developmental, metabolic, housekeeping functions. By complementing current knowledge emerging research, this aims to enhance understanding FGF-FGFR-mediated its implications for health disease, which will be crucial therapeutic development against FGF-related pathological conditions.

Language: Английский

Citations

4
Divergent destinies: insights into the molecular mechanisms underlying EPI and PE fate determination DOI Creative Commons
Paraskevi Athanasouli, Tijs Vanhessche, Frederic Lluı́s

et al.

Life Science Alliance, Journal Year: 2025, Volume and Issue: 8(3), P. e202403091 - e202403091

Published: Jan. 8, 2025

Mammalian pre-implantation development is entirely devoted to the specification of extra-embryonic lineages, which are fundamental for embryo morphogenesis and support. The second fate decision taken just before implantation, as defined by epiblast (EPI) primitive endoderm (PE) specification. Later, EPI forms proper PE contributes formation yolk sac. molecularly morphologically distinct lineages final step a multistage process, begins when bipotent progenitor cells diverge into separate fates. Despite advances in uncovering molecular mechanisms underlying differential transcriptional patterns that dictate how apparently identical make decisions lineage integrity maintained, detailed overview these still lacking. In this review, we dissect process four stages (initiation, specification, segregation, maintenance) provide comprehensive understanding involved establishment mouse. addition, discuss conservation key processes humans, based on most recent findings.

Language: Английский

Citations

0
Programming of pluripotency and the germ line co-evolved from a Nanog ancestor DOI Creative Commons

Darren Crowley,

Luke Simpson, Jodie Chatfield

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(3), P. 115396 - 115396

Published: March 1, 2025

Highlights•A Vent gene from an acorn worm possesses Nanog-like programming activity•The a sea anemone supports self-renewal but fails to reprogram•Vent and Nanog activities appear sub-functionalize in vertebrates•Nanog activity evolves coincidently with the evolution of mesodermSummaryFrancois Jacob proposed that evolutionary novelty arises through incremental tinkering pre-existing genetic mechanisms. Vertebrate was predicated on pluripotency, ability embryonic cells form somatic germ layers primordial (PGCs). The origins pluripotency remain unclear, as key regulators, such Nanog, are not conserved outside vertebrates. Given NANOG's role mammalian development, we hypothesized NANOG might exist ancestral invertebrate genes. Here, find hemichordate Saccoglossus kowalevskii exhibits activity, Nanog−/− mouse pre-induced pluripotent stem (iPSCs) NANOG-depleted axolotl embryos. cnidarian Nematostella vectensis showed partial whereas sponges vertebrates had no activity. VENTX knockdown axolotls revealed germline-competent mesoderm, which could rescue not. This suggests last deuterostome ancestor capable germline competence.Graphical abstract

Language: Английский

Citations

0
Role of tristability in the robustness of the differentiation mechanism DOI Creative Commons
Corentin Robert, Francisco Prista von Bonhorst,

Geneviéve Dupont

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(3), P. e0316666 - e0316666

Published: March 19, 2025

During cell differentiation, identical pluripotent cells undergo a specification process marked by changes in the expression of key genes, regulated transcription factors that can inhibit competing gene or activate their own transcription. This is orchestrated regulatory networks (GRNs), encompassing factors, biochemical reactions, and signalling cascades. Mathematical models for these GRNs have been proposed various contexts, to replicate observed robustness differentiation properties. includes reproducible proportions differentiated with respect parametric stochastic noise avoidance transitions between states. Understanding GRN components controlling features crucial. Our study thoroughly explored an extended version Toggle Switch model auto-activation loops. represents evolving from common progenitors one out two fates ( A B , bistable regime) or, additionally, remaining progenitor state C tristable regime). Such into populations three distinct during blastocyst formation mammals, where inner mass remain differentiate epiblast primitive endoderm. Systematic analysis revealed existence stable non-differentiated significantly impacts GRN’s against variations noise. reduces sensitivity parameters asymmetry prevents making after acquiring new identity. Stochastic enhances decreasing initial levels helping system escape fates, more efficient.

Language: Английский

Citations

0