Novel synthetic biology approaches for developmental systems

Ho, Coral; Morsut, Leonardo

doi:10.1016/j.stemcr.2021.04.007

Cited by 32 publications

(32 citation statements)

References 111 publications

(142 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The identification and characterization of these factors will ultimately allow implementation in simplified "toy models" (i.e. minimal models akin to the pendulum for physics 13 ) of synthetic development both in silico and in vitro [13][14][15][16][17][18][19][20] .…”

Section: Introductionmentioning

confidence: 99%

A parametrized computational framework for description and design of genetic circuits of morphogenesis based on contact-dependent signaling and changes in cell-cell adhesion

Morsut¹,

Lam²

2019

Preprint

Self Cite

View full text Add to dashboard Cite

Synthetic development is a nascent field of research that uses the tools of synthetic biology to design genetic programs directing cellular patterning and morphogenesis in higher eukaryotic cells, such as mammalian cells. Synthetic genetic networks comprising cell-cell communications and morphogenesis effectors (e.g. adhesion) are generated and integrated into a cellular genome. Current design methods for these genetic programs rely on trial and error, which limit the number of possible circuits and parameter ranges that can be explored. By contrast, computational models act as rapid testing platforms, revealing the networks, signals, and responses required for achieving robust target structures. Here we introduce a computational framework, based on cellular Potts, where contact dependent cell-cell signaling networks and cellular responses can be chosen in a modular fashion. We represent and tune a number of recently described synthetic morphogenic trajectories in silico, such as those resulting in multilayered synthetic spheroids. Our parameters were tuned using a comparison with published in vitro experimental results. Our tuned parameters were then used to design and explore novel developmental trajectories for the formation of elongated and oscillatory structures. Here, multiple rounds of optimization suggested critical parameters for the successful implementation of these trajectories. The framework that we develop here could function as a testing ground to explore how synthetic biology tools can be used to create particular multicellular trajectories, as well as for understanding both imagined and extant developmental trajectories.

show abstract

Section: Introductionmentioning

confidence: 99%

A parametrized computational framework for description and design of genetic circuits of morphogenesis based on contact-dependent signaling and changes in cell-cell adhesion

Morsut¹,

Lam²

2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Systems to externally induce the degradation of selected proteins [239][240][241] will allow the dissection of how specific proteins, for instance negative feedback regulators, affect signalling dynamics. (5) Synthetic biology and bioengineering approaches then allow researchers to build intercellular signalling networks in vitro, modulate them and test predictions on the functionality of these networks [159,160,242].…”

Section: Perspectivementioning

confidence: 99%

Signalling dynamics in embryonic development

Sonnen

Janda

2021

Biochemical Journal

View full text Add to dashboard Cite

In multicellular organisms, cellular behaviour is tightly regulated to allow proper embryonic development and maintenance of adult tissue. A critical component in this control is the communication between cells via signalling pathways, as errors in intercellular communication can induce developmental defects or diseases such as cancer. It has become clear over the last years that signalling is not static but varies in activity over time. Feedback mechanisms present in every signalling pathway lead to diverse dynamic phenotypes, such as transient activation, signal ramping or oscillations, occurring in a cell type- and stage-dependent manner. In cells, such dynamics can exert various functions that allow organisms to develop in a robust and reproducible way. Here, we focus on Erk, Wnt and Notch signalling pathways, which are dynamic in several tissue types and organisms, including the periodic segmentation of vertebrate embryos, and are often dysregulated in cancer. We will discuss how biochemical processes influence their dynamics and how these impact on cellular behaviour within multicellular systems.

show abstract

“…The field of synthetic developmental biology ( Davies, 2017 ; Ebrahimkhani and Ebisuya, 2019 ; Ho and Morsut, 2021 ; Santorelli et al, 2019 ; Schlissel and Li, 2020 ) seeks to understand the mechanisms of patterning and cell differentiation through the engineering of genetic circuits ( Cachat et al, 2016 ; Matsuda et al, 2015 ; Sekine et al, 2018 ). By re-engineering the Notch/Delta signalling cascade ( Fig.…”

Section: Introductionmentioning

confidence: 99%

SyNPL: Synthetic Notch pluripotent cell lines to monitor and manipulate cell interactions in vitro and in vivo

et al. 2022

View full text Add to dashboard Cite

Cell-cell interactions govern differentiation and cell competition in pluripotent cells during early development, but the investigation of such processes is hindered by a lack of efficient analysis tools. Here we introduce SyNPL: clonal pluripotent stem cell lines which employ optimised Synthetic Notch (SynNotch) technology to report cell-cell interactions between engineered “sender” and “receiver” cells in cultured pluripotent cells and chimaeric mouse embryos. A modular design makes it straightforward to adapt the system for programming differentiation decisions non-cell-autonomously in receiver cells in response to direct contact with sender cells. We demonstrate the utility of this system by enforcing neuronal differentiation at the boundary between two cell populations. In summary, we provide a new adaptation of SynNotch technology which could be used to identify cell interactions and to profile changes in gene or protein expression that result from direct cell-cell contact with defined cell populations in culture and in early embryos, and which can be customised to generate synthetic patterning of cell fate decisions.

show abstract

Novel synthetic biology approaches for developmental systems

Cited by 32 publications

References 111 publications

A parametrized computational framework for description and design of genetic circuits of morphogenesis based on contact-dependent signaling and changes in cell-cell adhesion

A parametrized computational framework for description and design of genetic circuits of morphogenesis based on contact-dependent signaling and changes in cell-cell adhesion

Signalling dynamics in embryonic development

SyNPL: Synthetic Notch pluripotent cell lines to monitor and manipulate cell interactions in vitro and in vivo

Contact Info

Product

Resources

About