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Article ; Online: The stem cell zoo for comparative studies of developmental tempo.

Lázaro, Jorge / Sochacki, Jaroslaw / Ebisuya, Miki

Current opinion in genetics & development

2024 Volume 84, Page(s) 102149

Abstract: The rate of development is highly variable across animal species. However, the mechanisms regulating developmental tempo have remained elusive due to difficulties in performing direct interspecies comparisons. Here, we discuss how pluripotent stem cell- ... ...

Abstract	The rate of development is highly variable across animal species. However, the mechanisms regulating developmental tempo have remained elusive due to difficulties in performing direct interspecies comparisons. Here, we discuss how pluripotent stem cell-based models of development can be used to investigate cell- and tissue-autonomous temporal processes. These systems enable quantitative comparisons of different animal species under similar experimental conditions. Moreover, the constantly growing stem cell zoo collection allows the extension of developmental studies to a great number of unconventional species. We argue that the stem cell zoo constitutes a powerful platform to perform comparative studies of developmental tempo, as well as to study other forms of biological time control such as species-specific lifespan, heart rate, and circadian clocks.
MeSH term(s)	Animals ; Circadian Clocks ; Pluripotent Stem Cells ; Species Specificity
Language	English
Publishing date	2024-01-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1077312-5
ISSN	1879-0380 ; 0959-437X
ISSN (online)	1879-0380
ISSN	0959-437X
DOI	10.1016/j.gde.2023.102149
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Article ; Online: Tension hones body segmentation around the clock.

Ebisuya, Miki / Trepat, Xavier

Nature

2022 Volume 605, Issue 7910, Page(s) 432–433

MeSH term(s)	Body Patterning ; Gene Expression Regulation, Developmental ; Somites
Language	English
Publishing date	2022-04-27
Publishing country	England
Document type	News ; Comment
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/d41586-022-00840-x
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Article: Self-organization of vascularized skeletal muscle from bovine embryonic stem cells.

Sanaki-Matsumiya, Marina / Villava, Casandra / Rappez, Luca / Haase, Kristina / Wu, Jun / Ebisuya, Miki

bioRxiv : the preprint server for biology

2024

Abstract: Cultured beef holds promising potential as an alternative to traditional meat options. While adult stem cells are commonly used as the cell source for cultured beef, their proliferation and differentiation capacities are limited. To produce cultured beef ...

Abstract	Cultured beef holds promising potential as an alternative to traditional meat options. While adult stem cells are commonly used as the cell source for cultured beef, their proliferation and differentiation capacities are limited. To produce cultured beef steaks, current manufacturing plans often require the separate preparation of multiple cell types and intricate engineering for assembling them into structured tissues. In this study, we propose and report the co-induction of skeletal muscle, neuronal, and endothelial cells from bovine embryonic stem cells (ESCs) and the self-organization of tissue structures in 2- and 3-dimensional cultures. Bovine myocytes were induced in a stepwise manner through the induction of presomitic mesoderm (PSM) from bovine ESCs. Muscle fibers with sarcomeres appeared within 15 days, displaying calcium oscillations responsive to inputs from co-induced bovine spinal neurons. Bovine endothelial cells were also co-induced via PSM, forming uniform vessel networks inside tissues. Our serum-free, rapid co-induction protocols represent a milestone toward self-organizing beef steaks with integrated vasculature and innervation.
Language	English
Publishing date	2024-03-25
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.22.586252
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Article ; Online: Scaling up complexity in synthetic developmental biology.

Martínez-Ara, Guillermo / Stapornwongkul, Kristina S / Ebisuya, Miki

Science (New York, N.Y.)

2022 Volume 378, Issue 6622, Page(s) 864–868

Abstract: The application of synthetic biology approaches to study development opens the possibility to build and manipulate developmental processes to understand them better. Researchers have reconstituted fundamental developmental processes, such as cell ... ...

Abstract	The application of synthetic biology approaches to study development opens the possibility to build and manipulate developmental processes to understand them better. Researchers have reconstituted fundamental developmental processes, such as cell patterning and sorting, by engineering gene circuits in vitro. Moreover, new tools have been created that allow for the control of developmental processes in more complex organoids and embryos. Synthetic approaches allow testing of which components are sufficient to reproduce a developmental process and under which conditions as well as what effect perturbations have on other processes. We envision that the future of synthetic developmental biology requires an increase in the diversity of available tools and further efforts to combine multiple developmental processes into one system.
MeSH term(s)	Developmental Biology/methods ; Gene Regulatory Networks ; Organoids ; Synthetic Biology/methods ; Cell Culture Techniques
Language	English
Publishing date	2022-11-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.add9666
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Article ; Online: Synthetic developmental biology: build and control multicellular systems.

Ebrahimkhani, Mo R / Ebisuya, Miki

Current opinion in chemical biology

2019 Volume 52, Page(s) 9–15

Abstract: Synthetic biology offers a bottom-up engineering approach that intends to understand complex systems via design-build-test cycles. Embryonic development comprises complex processes that originate at the level of gene regulatory networks in a cell and ... ...

Abstract	Synthetic biology offers a bottom-up engineering approach that intends to understand complex systems via design-build-test cycles. Embryonic development comprises complex processes that originate at the level of gene regulatory networks in a cell and emerge into collective cellular behaviors with multicellular forms and functions. Here, we review synthetic biology approaches to development that involve building de novo developmental trajectories or engineering control in stem cell-derived multicellular systems. The field of synthetic developmental biology is rapidly growing with the help of recent advances in artificial gene circuits, self-organizing organoids, and controllable tissue microenvironments. The outcome will be a blueprint to decode principles of morphogenesis and to create programmable organoids with novel designs or improved functions.
MeSH term(s)	Cell Communication ; Developmental Biology ; Embryonic Development ; Gene Regulatory Networks ; Morphogenesis ; Organoids ; Stem Cells/cytology ; Synthetic Biology
Language	English
Publishing date	2019-05-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1439176-4
ISSN	1879-0402 ; 1367-5931
ISSN (online)	1879-0402
ISSN	1367-5931
DOI	10.1016/j.cbpa.2019.04.006
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Article ; Online: What does time mean in development?

Ebisuya, Miki / Briscoe, James

Development (Cambridge, England)

2018 Volume 145, Issue 12

Abstract: Biology is dynamic. Timescales range from frenetic sub-second ion fluxes and enzymatic reactions to the glacial millions of years of evolutionary change. Falling somewhere in the middle of this range are the processes we usually study in development: ... ...

Abstract	Biology is dynamic. Timescales range from frenetic sub-second ion fluxes and enzymatic reactions to the glacial millions of years of evolutionary change. Falling somewhere in the middle of this range are the processes we usually study in development: cell division and differentiation, gene expression, cell-cell signalling, and morphogenesis. But what sets the tempo and manages the order of developmental events? Are the order and tempo different between species? How is the sequence of multiple events coordinated? Here, we discuss the importance of time for developing embryos, highlighting the necessity for global as well as cell-autonomous control. New reagents and tools in imaging and genomic engineering, combined with
MeSH term(s)	Animals ; Embryonic Development ; Gene Expression Regulation, Developmental ; Models, Biological ; Species Specificity ; Time Factors
Language	English
Publishing date	2018-06-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.164368
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Article ; Online: Arrested coalescence of multicellular aggregates.

Oriola, David / Marin-Riera, Miquel / Anlaş, Kerim / Gritti, Nicola / Sanaki-Matsumiya, Marina / Aalderink, Germaine / Ebisuya, Miki / Sharpe, James / Trivedi, Vikas

Soft matter

2022 Volume 18, Issue 19, Page(s) 3771–3780

Abstract: Multicellular aggregates are known to exhibit liquid-like properties. The fusion process of two cell aggregates is commonly studied as the coalescence of two viscous drops. However, tissues are complex materials and can exhibit viscoelastic behaviour. It ...

Abstract	Multicellular aggregates are known to exhibit liquid-like properties. The fusion process of two cell aggregates is commonly studied as the coalescence of two viscous drops. However, tissues are complex materials and can exhibit viscoelastic behaviour. It is known that elastic effects can prevent the complete fusion of two drops, a phenomenon known as arrested coalescence. Here we study this phenomenon in stem cell aggregates and provide a theoretical framework which agrees with the experiments. In addition, agent-based simulations show that active cell fluctuations can control a solid-to-fluid phase transition, revealing that arrested coalescence can be found in the vicinity of an unjamming transition. By analysing the dynamics of the fusion process and combining it with nanoindentation measurements, we obtain the effective viscosity, shear modulus and surface tension of the aggregates. More generally, our work provides a simple, fast and inexpensive method to characterize the mechanical properties of viscoelastic materials.
MeSH term(s)	Surface Tension ; Viscosity
Language	English
Publishing date	2022-05-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2191476-X
ISSN	1744-6848 ; 1744-683X
ISSN (online)	1744-6848
ISSN	1744-683X
DOI	10.1039/d2sm00063f
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Article ; Online: Periodic formation of epithelial somites from human pluripotent stem cells.

Sanaki-Matsumiya, Marina / Matsuda, Mitsuhiro / Gritti, Nicola / Nakaki, Fumio / Sharpe, James / Trivedi, Vikas / Ebisuya, Miki

Nature communications

2022 Volume 13, Issue 1, Page(s) 2325

Abstract: During embryonic development, epithelial cell blocks called somites are periodically formed according to the segmentation clock, becoming the foundation for the segmental pattern of the vertebral column. The process of somitogenesis has recently been ... ...

Abstract	During embryonic development, epithelial cell blocks called somites are periodically formed according to the segmentation clock, becoming the foundation for the segmental pattern of the vertebral column. The process of somitogenesis has recently been recapitulated with murine and human pluripotent stem cells. However, an in vitro model for human somitogenesis coupled with the segmentation clock and epithelialization is still missing. Here, we report the generation of human somitoids, organoids that periodically form pairs of epithelial somite-like structures. Somitoids display clear oscillations of the segmentation clock that coincide with the segmentation of the presomitic mesoderm. The resulting somites show anterior-posterior and apical-basal polarities. Matrigel is essential for epithelialization but dispensable for the differentiation into somite cells. The size of somites is rather constant, irrespective of the initial cell number. The amount of WNT signaling instructs the proportion of mesodermal lineages in somitoids. Somitoids provide a novel platform to study human somitogenesis.
MeSH term(s)	Animals ; Embryonic Development ; Humans ; Mesoderm ; Mice ; Pluripotent Stem Cells ; Receptors, Notch ; Somites
Chemical Substances	Receptors, Notch
Language	English
Publishing date	2022-04-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-29967-1
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Article ; Online: Synthetic mammalian pattern formation driven by differential diffusivity of Nodal and Lefty.

Sekine, Ryoji / Shibata, Tatsuo / Ebisuya, Miki

Nature communications

2018 Volume 9, Issue 1, Page(s) 5456

Abstract: A synthetic mammalian reaction-diffusion pattern has yet to be created, and Nodal-Lefty signaling has been proposed to meet conditions for pattern formation: Nodal is a short-range activator whereas Lefty is a long-range inhibitor. However, this pattern ... ...

Abstract	A synthetic mammalian reaction-diffusion pattern has yet to be created, and Nodal-Lefty signaling has been proposed to meet conditions for pattern formation: Nodal is a short-range activator whereas Lefty is a long-range inhibitor. However, this pattern forming possibility has never been directly tested, and the underlying mechanisms of differential diffusivity of Nodal and Lefty remain unclear. Here, through a combination of synthetic and theoretical approaches, we show that a reconstituted Nodal-Lefty network in mammalian cells spontaneously gives rise to a pattern. Surprisingly, extracellular Nodal is confined underneath the cells, resulting in a narrow distribution compared with Lefty. The short-range distribution requires the finger 1 domain of Nodal, and transplantation of the finger 1 domain into Lefty shortens the distribution of Lefty, successfully preventing pattern formation. These results indicate that the differences in localization and domain structures between Nodal and Lefty, combined with the activator-inhibitor topology, are sufficient for reaction-diffusion patterning.
MeSH term(s)	Body Patterning ; Cell Culture Techniques ; Diffusion ; HEK293 Cells ; Humans ; Left-Right Determination Factors/physiology ; Models, Biological ; Nodal Protein/physiology ; Synthetic Biology
Chemical Substances	Left-Right Determination Factors ; NODAL protein, human ; Nodal Protein
Language	English
Publishing date	2018-12-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-018-07847-x
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Article ; Online: Periodic formation of epithelial somites from human pluripotent stem cells

Marina Sanaki-Matsumiya / Mitsuhiro Matsuda / Nicola Gritti / Fumio Nakaki / James Sharpe / Vikas Trivedi / Miki Ebisuya

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 14

Abstract: Somitogenesis has been well characterized in model organisms, resulting in detailed description of the somite segmentation clock. Here they generate somitogenic organoids from human pluripotent stem cells that recapitulate somitogenesis, periodic ... ...

Abstract	Somitogenesis has been well characterized in model organisms, resulting in detailed description of the somite segmentation clock. Here they generate somitogenic organoids from human pluripotent stem cells that recapitulate somitogenesis, periodic segmentation, and proper polarity.
Keywords	Science ; Q
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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