All models are wrong, but some are useful: Establishing standards for stem cell-based embryo models DOI Creative Commons
Eszter Pósfai, Fredrik Lanner, Carla Mulas

et al.

Stem Cell Reports, Journal Year: 2021, Volume and Issue: 16(5), P. 1117 - 1141

Published: May 1, 2021

Detailed studies of the embryo allow an increasingly mechanistic understanding development, which has proved profound relevance to human disease. The last decade seen in vitro cultured stem cell-based models development flourish, provide alternative for accessible experimentation. However, usefulness any model will be determined by how accurately it reflects vivo embryonic and/or extent facilitates new discoveries. Stringent benchmarking is thus important consideration this growing field. Here we overview means evaluate both properties cells, building blocks most models, as well current and future models.

Language: Английский

The extracellular matrix in development DOI Creative Commons
David A. Cruz Walma, Kenneth M. Yamada

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

Citations

324

Mouse embryonic stem cells self-organize into trunk-like structures with neural tube and somites DOI
Jesse V. Veenvliet, Adriano Bolondi, Helene Kretzmer

et al.

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

Citations

270

Mechanisms of human embryo development: from cell fate to tissue shape and back DOI Creative Commons
Marta N. Shahbazi

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

Citations

163

A roadmap for the Human Developmental Cell Atlas DOI Open Access
Muzlifah Haniffa, Deanne Taylor, Sten Linnarsson

et al.

Nature, Journal Year: 2021, Volume and Issue: 597(7875), P. 196 - 205

Published: Sept. 8, 2021

Language: Английский

Citations

145

Regulation, functions and transmission of bivalent chromatin during mammalian development DOI
Trisha A. Macrae, Julie Fothergill-Robinson, Miguel Ramalho‐Santos

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 24(1), P. 6 - 26

Published: Aug. 26, 2022

Language: Английский

Citations

116

Mechanical Tension Promotes Formation of Gastrulation-like Nodes and Patterns Mesoderm Specification in Human Embryonic Stem Cells DOI Creative Commons
Jonathon M. Muncie, Nadia M.E. Ayad, Johnathon N. Lakins

et al.

Developmental Cell, Journal Year: 2020, Volume and Issue: 55(6), P. 679 - 694.e11

Published: Nov. 17, 2020

Language: Английский

Citations

112

Viscoelasticity and Adhesion Signaling in Biomaterials Control Human Pluripotent Stem Cell Morphogenesis in 3D Culture DOI
Dhiraj Indana, Pranay Agarwal, Nidhi Bhutani

et al.

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(43)

Published: Sept. 9, 2021

Abstract Organoids are lumen‐containing multicellular structures that recapitulate key features of the organs, and increasingly used in models disease, drug testing, regenerative medicine. Recent work has 3D culture to form organoids from human induced pluripotent stem cells (hiPSCs) reconstituted basement membrane (rBM) matrices. However, rBM matrices offer little control over microenvironment. More generally, role matrix viscoelasticity directing lumen formation remains unknown. Here, viscoelastic alginate hydrogels with independently tunable stress relaxation (viscoelasticity), stiffness, arginine–glycine–aspartate (RGD) ligand density study hiPSC morphogenesis culture. A phase diagram shows how these properties is reported. Higher RGD fast promote viability, proliferation, apicobasal polarization, formation, while slow at low densities triggers apoptosis. Notably, hiPSCs maintain pluripotency for much longer times than reported Lumen regulated by actomyosin contractility accompanied translocation Yes‐associated protein (YAP) nucleus cytoplasm. The results reveal as a potent factor regulating cell provide new insights into engineered biomaterials may be leveraged build organoids.

Language: Английский

Citations

100

High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures DOI Creative Commons
Kyaw Thu Minn, Yuheng C. Fu, Shenghua He

et al.

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Nov. 18, 2020

During mammalian gastrulation, germ layers arise and are shaped into the body plan while extraembryonic sustain embryo. Human embryonic stem cells, cultured with BMP4 on extracellular matrix micro-discs, reproducibly differentiate gastruloids, expressing markers of cells in radial arrangement. Using single-cell RNA sequencing cross-species comparisons mouse, cynomolgus monkey gastrulae, post-implantation human embryos, we reveal that gastruloids contain transcriptionally similar to epiblast, ectoderm, mesoderm, endoderm, primordial trophectoderm, amnion. Upon gastruloid dissociation, single reseeded onto micro-discs were motile aggregated same but segregated from distinct cell types. Ectodermal endodermal mixed mesodermal cells. Our work demonstrates system models primate-specific features embryogenesis, exhibit evolutionarily conserved sorting behaviors. This generates a resource for transcriptomes differentiated stereotyped

Language: Английский

Citations

96

Construction of a mammalian embryo model from stem cells organized by a morphogen signalling centre DOI Creative Commons
Peng‐Fei Xu, Ricardo Moraes Borges, Jonathan Fillâtre

et al.

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

Published: June 2, 2021

Abstract Generating properly differentiated embryonic structures in vitro from pluripotent stem cells remains a challenge. Here we show that instruction of aggregates mouse with an experimentally engineered morphogen signalling centre, functions as organizer, results the development embryo-like entities (embryoids). In situ hybridization, immunolabelling, cell tracking and transcriptomic analyses these embryoids form three germ layers through gastrulation process they exhibit wide range developmental structures, highly similar to neurula-stage embryos. Embryoids are organized around axial chordamesoderm, dorsal neural plate displays histological properties murine embryo neuroepithelium folds into tube patterned antero-posteriorly posterior midbrain tip tail. Lateral display somitic intermediate mesoderm, beating cardiac tissue anteriorly formation vasculature network. Ventrally, differentiate primitive gut tube, which is both dorso-ventrally. Altogether, provide model mammalian extensive layer derivatives promises be powerful tool for studies disease modelling.

Language: Английский

Citations

87

Rebooting the Epigenomes during Mammalian Early Embryogenesis DOI
Weikun Xia, Wei Xie

Stem Cell Reports, Journal Year: 2020, Volume and Issue: 15(6), P. 1158 - 1175

Published: Oct. 8, 2020

Language: Английский

Citations

78