How Daughters Tell Their Mums to Behave.
TL;DR: In this article, the tensile state of skin suprabasal cells non-autonomously regulates stem cell behavior in the basal layer of the skin, and it is shown that these cells develop or get repaired synchronously so as to remain properly organized.
About: This article is published in Developmental Cell.The article was published on 2021-01-25. It has received 2 citations till now.
Citations
More filters
TL;DR: In this article , a morpho-elastic model based on Neo-Hookean elasticity with anisotropic growth is presented to quantitatively explain the growth dynamics of human induced pluripotent stem cells (hiPSCs).
Abstract: Human induced pluripotent stem cells (hiPSCs) are a promising cellular source in cell therapies or regenerative medicine and they allow to address fundamental mechanisms in embryo-genesis. However, their culture to provide large amounts of high quality stem cells remains challenging. Here, using an encapsulation microfluidic device, we observe that hiPSCs self-organize into cysts, which are spherical closed epithelia reminiscent of the early stages of in vitro embryo models. We monitor their morphology, organization and growth in a pseudo-stratified epithelium before and after they get confined by the capsule wall. Then, we present a morpho-elastic model to quantitatively explain the growth dynamics. The model based on Neo-Hookean elasticity with anisotropic growth shows that the stresses, concentrated within the cyst, remain at a low level. Cyst growth is shown to be quasi-exponential, slightly reduced by a compression-induced correction. We hypothesize that this peculiar morphological dynamics, which is controlled by elasticity and anisotropic growth, might provide new strategies to optimize the production of medical grade hiPSCs.
1 citations
TL;DR: In this paper , the effects of microgravity on soft matter morphogenesis have been documented in countless experiments, but physical understanding is still lacking in many cases, and the importance of building physical models for understanding the experimental results available.
Abstract: Abstract The effects of microgravity on soft matter morphogenesis have been documented in countless experiments, but physical understanding is still lacking in many cases. Here we review how gravity affects shape emergence and pattern formation for both inert matter and living systems of different biological complexities. We highlight the importance of building physical models for understanding the experimental results available. Answering these fundamental questions will not only solve basic scientific problems, but will also enable several industrial applications relevant to space exploration.
References
More filters
TL;DR: The findings suggest that the C. elegans hemidesmosome is not only an attachment structure, but also a mechanosensor that responds to tension by triggering signalling processes that promote epithelial morphogenesis or wound healing in other organisms in which epithelial cells adhere to tension-generating contractile cells.
Abstract: Mechanotransduction refers to the transformation of physical forces into chemical signals. It generally involves stretch-sensitive channels or conformational change of cytoskeleton-associated proteins. Mechanotransduction is crucial for the physiology of several organs and for cell migration. The extent to which mechanical inputs contribute to development, and how they do this, remains poorly defined. Here we show that a mechanotransduction pathway operates between the body-wall muscles of Caenorhabditis elegans and the epidermis. This pathway involves, in addition to a Rac GTPase, three signalling proteins found at the hemidesmosome: p21-activated kinase (PAK-1), the adaptor GIT-1 and its partner PIX-1. The phosphorylation of intermediate filaments is one output of this pathway. Tension exerted by adjacent muscles or externally exerted mechanical pressure maintains GIT-1 at hemidesmosomes and stimulates PAK-1 activity through PIX-1 and Rac. This pathway promotes the maturation of a hemidesmosome into a junction that can resist mechanical stress and contributes to coordinating the morphogenesis of epidermal and muscle tissues. Our findings suggest that the C. elegans hemidesmosome is not only an attachment structure, but also a mechanosensor that responds to tension by triggering signalling processes. We suggest that similar pathways could promote epithelial morphogenesis or wound healing in other organisms in which epithelial cells adhere to tension-generating contractile cells.
264 citations
TL;DR: During embryonic development, epidermal basal layer crowding generates local changes in cell shape, cortical tension, and adhesion that initiate differentiation and delamination that generate multilayered tissue.
Abstract: To establish and maintain organ structure and function, tissues need to balance stem cell proliferation and differentiation rates and coordinate cell fate with position. By quantifying and modelling tissue stress and deformation in the mammalian epidermis, we find that this balance is coordinated through local mechanical forces generated by cell division and delamination. Proliferation within the basal stem/progenitor layer, which displays features of a jammed, solid-like state, leads to crowding, thereby locally distorting cell shape and stress distribution. The resulting decrease in cortical tension and increased cell–cell adhesion trigger differentiation and subsequent delamination, reinstating basal cell layer density. After delamination, cells establish a high-tension state as they increase myosin II activity and convert to E-cadherin-dominated adhesion, thereby reinforcing the boundary between basal and suprabasal layers. Our results uncover how biomechanical signalling integrates single-cell behaviours to couple proliferation, cell fate and positioning to generate a multilayered tissue. Mechanics of epidermal differentiation Miroshnikova et al. find that during embryonic development, epidermal basal layer crowding generates local changes in cell shape, cortical tension, and adhesion that initiate differentiation and delamination
206 citations
TL;DR: Using the nascent skin of the developing chicken embryo as a model system, this work finds that morphological and molecular symmetries are simultaneously broken by an emergent process of cellular self-organization.
Abstract: The spacing of hair in mammals and feathers in birds is one of the most apparent morphological features of the skin. This pattern arises when uniform fields of progenitor cells diversify their molecular fate while adopting higher-order structure. Using the nascent skin of the developing chicken embryo as a model system, we find that morphological and molecular symmetries are simultaneously broken by an emergent process of cellular self-organization. The key initiators of heterogeneity are dermal progenitors, which spontaneously aggregate through contractility-driven cellular pulling. Concurrently, this dermal cell aggregation triggers the mechanosensitive activation of β-catenin in adjacent epidermal cells, initiating the follicle gene expression program. Taken together, this mechanism provides a means of integrating mechanical and molecular perspectives of organ formation.
171 citations
TL;DR: St stereotyped differentiation of airway smooth muscle adjacent to nascent epithelial buds is revealed and it is suggested that localized smooth muscle wrapping at the cleft site is required for terminal bifurcation during airway branching morphogenesis.
136 citations
TL;DR: Single-cell analysis in a mouse model of skin stretching shows that stretching causes a transient expansion bias in a population of epidermal stem cells, which is associated with chromatin remodelling and changes in transcriptional profiles.
Abstract: The ability of the skin to grow in response to stretching has been exploited in reconstructive surgery1. Although the response of epidermal cells to stretching has been studied in vitro2,3, it remains unclear how mechanical forces affect their behaviour in vivo. Here we develop a mouse model in which the consequences of stretching on skin epidermis can be studied at single-cell resolution. Using a multidisciplinary approach that combines clonal analysis with quantitative modelling and single-cell RNA sequencing, we show that stretching induces skin expansion by creating a transient bias in the renewal activity of epidermal stem cells, while a second subpopulation of basal progenitors remains committed to differentiation. Transcriptional and chromatin profiling identifies how cell states and gene-regulatory networks are modulated by stretching. Using pharmacological inhibitors and mouse mutants, we define the step-by-step mechanisms that control stretch-mediated tissue expansion at single-cell resolution in vivo. Single-cell analysis in a mouse model of skin stretching shows that stretching causes a transient expansion bias in a population of epidermal stem cells, which is associated with chromatin remodelling and changes in transcriptional profiles.
96 citations