Human placenta and trophoblast development: key molecular mechanisms and model systems

Cellular and Molecular Life Sciences, Journal Year: 2019, Volume and Issue: 76(18), P. 3479 - 3496

Published: May 3, 2019

Abnormal placentation is considered as an underlying cause of various pregnancy complications such miscarriage, preeclampsia and intrauterine growth restriction, the latter increasing risk for development severe disorders in later life cardiovascular disease type 2 diabetes. Despite their importance, molecular mechanisms governing human placental formation trophoblast cell lineage specification differentiation have been poorly unravelled, mostly due to lack appropriate cellular model systems. However, over past few years major progress has made by establishing self-renewing stem cells 3-dimensional organoids from blastocysts early tissues opening path detailed investigations. Herein, we summarize present knowledge about development, its cells, progenitors differentiated types epithelium villous core. Anatomy placenta, current systems, critical key regulatory factors signalling cascades will be elucidated. In this context, discuss role developmental pathways Wingless Notch, controlling stemness/differentiation invasive progenitors, respectively.

Language: Английский

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Integrin trafficking in cells and tissues

Nature Cell Biology, Journal Year: 2018, Volume and Issue: 21(2), P. 122 - 132

Published: Nov. 22, 2018

Language: Английский

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The extracellular matrix in development

Development, Journal Year: 2020, Volume and Issue: 147(10)

Published: May 15, 2020

ABSTRACT As the crucial non-cellular component of tissues, extracellular matrix (ECM) provides both physical support and signaling regulation to cells. Some ECM molecules provide a fibrillar environment around cells, while others sheet-like basement membrane scaffold beneath epithelial In this Review, we focus on recent studies investigating mechanical, biophysical cues provided developing tissues by different types in variety organisms. addition, discuss how helps regulate tissue morphology during embryonic development governing key elements cell shape, adhesion, migration differentiation.

Language: Английский

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Mouse embryonic stem cells self-organize into trunk-like structures with neural tube and somites

Science, Journal Year: 2020, Volume and Issue: 370(6522)

Published: Dec. 10, 2020

Post-implantation embryogenesis is a highly dynamic process comprising multiple lineage decisions and morphogenetic changes that are inaccessible to deep analysis in vivo. We found pluripotent mouse embryonic stem cells (mESCs) form aggregates upon embedding an extracellular matrix compound induce the formation of organized "trunk-like structures" (TLSs) neural tube somites. Comparative single-cell RNA sequencing confirmed this analogous development follows same stepwise gene-regulatory program. Tbx6 knockout TLSs developed additional tubes mirroring mutant phenotype, chemical modulation could excess somite formation. thus reveal advanced level self-organization provide powerful platform for investigating post-implantation dish.

Language: Английский

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Deconvolution of single-cell multi-omics layers reveals regulatory heterogeneity

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Jan. 28, 2019

Integrative analysis of multi-omics layers at single cell level is critical for accurate dissection cell-to-cell variation within certain populations. Here we report scCAT-seq, a technique simultaneously assaying chromatin accessibility and the transcriptome same cell. We show that combined signatures enable construction regulatory relationships between cis-regulatory elements target genes single-cell resolution, providing new dimension features helps direct discovery patterns specific to distinct identities. Moreover, generate first integrated map in early embryos demonstrate robustness scCAT-seq precise master transcription factors cells states. The ability obtain these two omics data will help provide more definitions "single state" deconvolution heterogeneity from complex

Language: Английский

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Self-organization of stem cells into embryos: A window on early mammalian development

Science, Journal Year: 2019, Volume and Issue: 364(6444), P. 948 - 951

Published: June 6, 2019

Embryonic development is orchestrated by robust and complex regulatory mechanisms acting at different scales of organization. In vivo studies are particularly challenging for mammals after implantation, owing to the small size inaccessibility embryo. The generation stem cell models embryo represents a powerful system with which dissect this complexity. Control geometry, modulation physical environment, priming chemical signals reveal intrinsic capacity embryonic cells make patterns. Adding extraembryonic lineages generates three-dimensional that more autonomous from environment recapitulate many features pre- postimplantation mouse embryo, including gastrulation. Here, we review principles self-organization how they set in motion create an

Language: Английский

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Human brain organogenesis: Toward a cellular understanding of development and disease

Cell, Journal Year: 2021, Volume and Issue: 185(1), P. 42 - 61

Published: Nov. 11, 2021

Language: Английский

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Dissecting primate early post-implantation development using long-term in vitro embryo culture

Science, Journal Year: 2019, Volume and Issue: 366(6467)

Published: Oct. 31, 2019

The transition from peri-implantation to gastrulation in mammals entails the specification and organization of lineage progenitors into a body plan. Technical ethical challenges have limited understanding cellular molecular mechanisms that underlie this transition. We established culture system enabled development cynomolgus monkey embryos vitro for up 20 days. Cultured underwent key primate developmental stages, including segregation, bilaminar disc formation, amniotic yolk sac cavitation, primordial germ cell-like cell (PGCLC) differentiation. Single-cell RNA-sequencing analysis revealed trajectories primitive endoderm, trophectoderm, epiblast lineages, PGCLCs. Analysis single-cell chromatin accessibility identified transcription factors specifying each type. Our results reveal critical events complex underlying nonhuman embryogenesis early postimplantation period, with possible relevance human development.

Language: Английский

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Mechanisms of human embryo development: from cell fate to tissue shape and back

Development, Journal Year: 2020, Volume and Issue: 147(14)

Published: July 15, 2020

Gene regulatory networks and tissue morphogenetic events drive the emergence of shape function: pillars embryo development. Although model systems offer a window into molecular biology cell fate shape, mechanistic studies our own development have so far been technically ethically challenging. However, recent technical developments provide tools to describe, manipulate mimic human embryos in dish, thus opening new avenue exploring Here, I discuss evidence that supports role for crosstalk between during early embryogenesis. This is critical developmental period, when body plan laid out many pregnancies fail. Dissecting basic mechanisms coordinate will generate an integrated understanding embryogenesis strategies therapeutic intervention pregnancy loss.

Language: Английский

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Reconstructing aspects of human embryogenesis with pluripotent stem cells

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 21, 2021

Abstract Understanding human development is of fundamental biological and clinical importance. Despite its significance, mechanisms behind embryogenesis remain largely unknown. Here, we attempt to model early embryo with expanded pluripotent stem cells (EPSCs) in 3-dimensions. We define a protocol that allows us generate self-organizing cystic structures from EPSCs display some hallmarks embryogenesis. These mimic polarization cavitation characteristic pre-implantation leading blastocyst morphology formation the transition post-implantation-like organization upon extended culture. Single-cell RNA sequencing these reveals subsets bearing resemblance epiblast, hypoblast trophectoderm lineages. Nevertheless, significant divergences natural blastocysts persist key markers, signalling pathways point towards ways which transcriptional-level cell identities may diverge models embryo. Thus, this platform provides insights into design

Language: Английский

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