Modular derivation of diverse, regionally discrete human posterior CNS neurons enables discovery of transcriptomic patterns DOI Creative Commons
Nisha Iyer, Junha Shin,

Stephanie Cuskey

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(39)

Published: Sept. 30, 2022

Our inability to derive the neuronal diversity that comprises posterior central nervous system (pCNS) using human pluripotent stem cells (hPSCs) poses an impediment understanding neurodevelopment and disease in hindbrain spinal cord. Here, we establish a modular, monolayer differentiation paradigm recapitulates both rostrocaudal (R/C) dorsoventral (D/V) patterning, enabling derivation of diverse pCNS neurons with discrete regional specificity. First, neuromesodermal progenitors (NMPs) HOX profiles are converted (pCNSPs). Then, by tuning D/V signaling, pCNSPs directed locomotor or somatosensory neurons. Expansive single-cell RNA-sequencing (scRNA-seq) analysis coupled novel computational pipeline allowed us detect hundreds transcriptional markers within region-specific phenotypes, discovery gene expression patterns across R/C developmental axes. These findings highlight potential these resources advance mechanistic development, enhance vitro models, inform therapeutic strategies.

Language: Английский

3D gastruloids: a novel frontier in stem cell-based in vitro modeling of mammalian gastrulation DOI Creative Commons
Susanne C. van den Brink, Alexander van Oudenaarden

Trends in Cell Biology, Journal Year: 2021, Volume and Issue: 31(9), P. 747 - 759

Published: July 22, 2021

3D gastruloids, aggregates of embryonic stem cells that recapitulate key aspects gastrula-stage embryos, have emerged as a powerful tool to study the early stages mammalian post-implantation development in vitro. Owing their tractable nature and relative ease by which they can be generated large numbers, gastruloids provide an unparalleled opportunity normal pathological embryogenesis from bottom-up perspective high-throughput manner. Here, we review how gastruloid models exploited deepen our understanding development. In addition, discuss current limitations, potential clinical applications, ethical implications this emerging model system.

Language: Английский

Citations

90
Self-organizing models of human trunk organogenesis recapitulate spinal cord and spine co-morphogenesis DOI
Simona Gribaudo,

Rémi Robert,

Björn van Sambeek

et al.

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 42(8), P. 1243 - 1253

Published: Sept. 14, 2023

Language: Английский

Citations

40
Notochord and axial progenitor generation by timely BMP and NODAL inhibition during vertebrate trunk formation DOI Creative Commons
Tiago Rito, Ashley R.G. Libby, Madeleine Demuth

et al.

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

Published: Feb. 28, 2023

Abstract The formation of the vertebrate body involves coordinated and progressive production trunk tissues from progenitors located in posterior embryo. In vitro models based on pluripotent stem cells (PSCs) replicate aspects this process, but they lack some tissue components normally present trunk. Most strikingly, notochord, a hallmark chordates source midline signals that pattern surrounding tissues, is absent current human formation. To investigate how formed, we performed single-cell transcriptomic analysis chick embryos. This delineated molecularly discrete progenitor populations, which spatially locate embryo, compare across species, relate to signalling activity. Guided by map, determined differentiating PSCs develop stereotypical spatial organization types. We found LATS1/2 repression YAP activity, conjunction with FGF-mediated MAPK activation, induced transcription factor Bra/TBXT facilitated WNT signaling. addition, inhibiting WNT-induced NODAL BMP signaling cascade at appropriate time regulated proportions different types produced, including notochordal cells. used information create an integrated 3D model gastrulation undergoing morphogenetic movements produce elongated structures notochord patterned neural Together data provide insight into mechanisms responsible for comprise pave way future studies patterning tissue-like environment.

Language: Английский

Citations

24
Retinoic acid induces human gastruloids with posterior embryo-like structures DOI Creative Commons
Nobuhiko Hamazaki, Wei Yang, Connor Kubo

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(10), P. 1790 - 1803

Published: Aug. 20, 2024

Abstract Gastruloids are a powerful in vitro model of early human development. However, although elongated and composed all three germ layers, gastruloids do not morphologically resemble post-implantation embryos. Here we show that an pulse retinoic acid (RA), together with later Matrigel, robustly induces posterior embryo-like morphological structures, including neural tube flanked by segmented somites diverse cell types, crest, progenitors, renal progenitors myocytes. Through silico staging based on single-cell RNA sequencing, find RA-gastruloids progress further than other or mouse embryo models, aligning to E9.5 CS11 cynomolgus monkey We leverage chemical genetic perturbations confirm WNT BMP signalling regulate somite formation length the context, while transcription factors TBX6 PAX3 underpin presomitic mesoderm respectively. Looking forward, robust, scalable for decoding embryogenesis.

Language: Английский

Citations

10
Sculpting with stem cells: how models of embryo development take shape DOI Creative Commons
Jesse V. Veenvliet, Pierre‐François Lenne, David A. Turner

et al.

Development, Journal Year: 2021, Volume and Issue: 148(24)

Published: Dec. 15, 2021

ABSTRACT During embryogenesis, organisms acquire their shape given boundary conditions that impose geometrical, mechanical and biochemical constraints. A detailed integrative understanding how these morphogenetic information modules pattern the mammalian embryo is still lacking, mostly owing to inaccessibility of in vivo for direct observation manipulation. These impediments are circumvented by developmental engineering embryo-like structures (stembryos) from pluripotent stem cells easy access, track, manipulate scale. Here, we explain unlocking distinct levels architecture through controlled modulations cellular environment enables identification minimal sets inputs necessary embryo. We detail this can be complemented with precise measurements manipulations tissue biochemistry, mechanics geometry across spatial temporal scales provide insights into mechanochemical feedback loops governing morphogenesis. Finally, discuss how, even absence active manipulations, stembryos display intrinsic phenotypic variability leveraged define constraints ensure reproducible morphogenesis vivo.

Language: Английский

Citations

44
Engineering multiscale structural orders for high-fidelity embryoids and organoids DOI Creative Commons
Yue Shao, Jianping Fu

Cell stem cell, Journal Year: 2022, Volume and Issue: 29(5), P. 722 - 743

Published: May 1, 2022

Language: Английский

Citations

36
Overview of Neural Tube Defects: Gene–Environment Interactions, Preventative Approaches and Future Perspectives DOI Creative Commons
Jasmina Isaković, Iva Šimunić, Denis Jagečić

et al.

Biomedicines, Journal Year: 2022, Volume and Issue: 10(5), P. 965 - 965

Published: April 21, 2022

Neural tube defects (NTDs) are the second most common congenital malformations of humans, characterized by impaired development central nervous system. Even though etiology birth remains undetermined, genetic and environmental risk factors in background NTDs have been identified extensively reported. On top nutritional risks which include mutations both coding non-coding regions maternal folate status, respectively, recent years seen a rise identification variety teratogens that could be implicated NTD development. These polycyclic aromatic hydrocarbons, arsenic, pesticides, hyperthermia antibiotics as well pain seizure medication. With an increase understanding leading to formation, preventative treatment approaches witnessed great advances throughout years. While approach includes folic acid food fortification suggested inositol supplementation, management differ greatly depending on developmental stage site lesion prenatal surgery, stem cell transplantation postnatal surgery. Because still represent large health financial burden for patient society whole, it is crucial investigate potential develop novel order fully prevent this category disorders.

Language: Английский

Citations

32
Building consensus in neuromesodermal research: Current advances and future biomedical perspectives DOI
Anahí Binagui-Casas, André Dias, Charlène Guillot

et al.

Current Opinion in Cell Biology, Journal Year: 2021, Volume and Issue: 73, P. 133 - 140

Published: Oct. 28, 2021

Language: Английский

Citations

39
Hydrogel Mechanics Influence the Growth and Development of Embedded Brain Organoids DOI
Camille Cassel de Camps,

Saba Aslani,

Nicholas A. Stylianesis

et al.

ACS Applied Bio Materials, Journal Year: 2021, Volume and Issue: 5(1), P. 214 - 224

Published: Dec. 22, 2021

Brain organoids are three-dimensional, tissue-engineered neural models derived from induced pluripotent stem cells that enable studies of neurodevelopmental and disease processes. Mechanical properties the microenvironment known to be critical parameters in tissue engineering, but mechanical consequences encapsulating matrix on brain organoid growth development remain undefined. Here, Matrigel was modified with an interpenetrating network (IPN) alginate, tune matrix. grown IPNs were viable, characteristic formation neuroepithelial buds. However, significantly restricted stiffest tested. Moreover, stiffer matrixes skewed cell populations toward mature neuronal phenotypes, fewer smaller rosettes. These findings demonstrate mechanics culture environment important show self-organizing capacity subsequent architecture can modulated by forces arising growth-induced compression surrounding This study therefore suggests carefully designing encapsulation materials is a potential strategy direct maturation desired structures.

Language: Английский

Citations

39
A new era of stem cell and developmental biology: from blastoids to synthetic embryos and beyond DOI Creative Commons
Yunhee Kim, I.S. Kim, Kunyoo Shin

et al.

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(10), P. 2127 - 2137

Published: Oct. 2, 2023

Abstract Recent discoveries in stem cell and developmental biology have introduced a new era marked by the generation of vitro models that recapitulate early mammalian development, providing unprecedented opportunities for extensive research embryogenesis. Here, we present an overview current techniques model embryogenesis, specifically noting created from cells derived two significant species: Homo sapiens , its high relevance, Mus musculus historically common technically advanced organism. We aim to provide holistic understanding these tracing historical background progress made discussing fundamental underlying principles. At each stage, corresponding vivo embryo further discuss how may be used diseases. Through discussion as well their potential applications future challenges, hope demonstrate innovative advances developed actualize clinical practice.

Language: Английский

Citations

16