Programming Morphogenesis through Systems and Synthetic Biology

Abstract

Mammalian tissue development is an intricate, spatiotemporal process of self-organization that emerges from gene regulatory networks of differentiating stem cells. A major goal in stem cell biology is to gain a sufficient understanding of gene regulatory networks and cell-cell interactions to enable the reliable and robust engineering of morphogenesis. Here, we review advances in synthetic biology, single cell genomics, and multiscale modeling, which, when synthesized, provide a framework to achieve the ambitious goal of programming morphogenesis in complex tissues and organoids.

Self‐organizing hair peg‐like structures from dissociated skin progenitor cells: New insights for human hair follicle organoid engineering and Turing patterning in an asymmetric morphogenetic field

“…On some occasions, cells need “help” to interact with other cells or require particular molecular signals to move forward to the next stage. Currently, in the emerging field of synthetic biology, methods are under development to provide cells with “help” in topological arrangement or molecular signalling at the right time and place …”

“…Currently, in the emerging field of synthetic biology, methods are under development to provide cells with "help" in topological arrangement [11,12] or molecular signalling at the right time and place. [13] But, to effectively adopt the synthetic biology approach, we must learn more about organoid cultures made of cells from different ages, locations or species, so we can apply key molecules to restore hair forming ability. [4] To this end, we sought to develop a three-dimensional, culture system in which different types of skin progenitors, such as epidermal-or dermal-like somatic cells, embryonic stem cells or iPS cells, can be guided to form ectodermal organs in a planar configuration ( Figure S1).…”

Rational programming of history-dependent logic in cellular populations

“…Cellular sensors could perform temporal logic analysis for diagnostics, environmental, or manufacturing applications. Finally, sequential programs would support iterative, ordered assembly of synthetic biological architectures for tissue and biomaterial engineering (70,71).…”

The Cognitive Lens: a primer on conceptual tools for analysing information processing in developmental and regenerative morphogenesis

“…We have two main aims in introducing the Cognitive Lens, which is not yet often used outside of behavioural studies and neural systems. First, to briefly overview the idea (fully developed elsewhere, [28][29][30]) that a mechanism-based (bottom-up) perspective can be complemented with a cybernetic, top-down one for more efficient control of large-scale pattern in regenerative medicine and synthetic morphology settings. Second, to introduce biologists to deep concepts from other fields and illustrate their interrelationships, in order to lower the barrier for the application royalsocietypublishing.org/journal/rstb Phil.…”