scholarly journals Stochastic Single Cell Behaviour Leads to Robust Horizontal Cell Layer Formation in the Vertebrate Retina

2019 ◽  
Author(s):  
Rana Amini ◽  
Anastasia Labudina ◽  
Caren Norden

ABSTRACTDevelopmental programs that arrange cells and tissues into patterned organs are remarkably robust. In the developing vertebrate retina for example, neurons reproducibly assemble into distinct layers giving the mature organ its overall structured appearance. This stereotypic neuronal arrangement, termed lamination, is important for efficient neuronal connectivity. While retinal lamination is conserved in many vertebrates including humans, how it emerges from single cell behaviour is not fully understood. To shed light on this question, we here investigated the formation of the retinal horizontal cell layer. Using in vivo light sheet imaging of the developing zebrafish retina, we generated a comprehensive quantitative analysis of horizontal single cell behaviour from birth to final positioning. Interestingly, we find that all parameters analyzed including cell cycle dynamics, migration paths and kinetics as well as sister cell dispersal are very heterogeneous. Thus, horizontal cells show individual non-stereotypic behaviour before final positioning. Yet, these initially stochastic cell dynamics always generate the correct laminar pattern. Consequently, our data shows that lamination of the vertebrate retina contains a yet underexplored extent of single cell stochasticity.

Development ◽  
2019 ◽  
Vol 146 (12) ◽  
pp. dev173450 ◽  
Author(s):  
Rana Amini ◽  
Anastasia A. Labudina ◽  
Caren Norden

Biochemistry ◽  
2017 ◽  
Vol 57 (1) ◽  
pp. 108-116 ◽  
Author(s):  
Jongchan Yeo ◽  
Andrew B. Dippel ◽  
Xin C. Wang ◽  
Ming C. Hammond

Neuron ◽  
2007 ◽  
Vol 56 (4) ◽  
pp. 597-603 ◽  
Author(s):  
Leanne Godinho ◽  
Philip R. Williams ◽  
Yvonne Claassen ◽  
Elayne Provost ◽  
Steven D. Leach ◽  
...  

2017 ◽  
Author(s):  
Rosanna C. G. Smith ◽  
Ben D. MacArthur

AbstractPurpose of ReviewTo outline how ideas from Information Theory may be used to analyze single cell data and better understand stem cell behaviour.Recent findingsRecent technological breakthroughs in single cell profiling have made it possible to interrogate cell-to-cell variability in a multitude of contexts, including the role it plays in stem cell dynamics. Here we review how measures from information theory are being used to extract biological meaning from the complex, high-dimensional and noisy datasets that arise from single cell profiling experiments. We also discuss how concepts linking information theory and statistical mechanics are being used to provide insight into cellular identity, variability and dynamics.SummaryWe provide a brief introduction to some basic notions from information theory and how they may be used to understand stem cell identities at the single cell level. We also discuss how work in this area might develop in the near future.


Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 797
Author(s):  
Lanpeng Chen ◽  
Maciej Boleslaw Olszewski ◽  
Marianna Kruithof-de Julio ◽  
B. Ewa Snaar-Jagalska

To visually and genetically trace single-cell dynamics of human prostate cancer (PCa) cells at the early stage of metastasis, a zebrafish (ZF) xenograft model was employed. The phenotypes of intravenously transplanted fluorescent cells were monitored by high-resolution, single-cell intravital confocal and light-sheet imaging. Engrafted osteotropic, androgen independent PCa cells were extravasated from caudle vein, invaded the neighboring tissue, proliferated and formed experimental metastases around caudal hematopoietic tissue (CHT) in four days. Gene expression comparison between cells in culture and in CHT revealed that engrafted PCa cells responded to the ZF microenvironment by elevating expression of epithelial–mesenchymal transition (EMT) and stemness markers. Next, metastatic potentials of ALDHhi cancer stem-like cells (CSCs) and ALDHlow non-CSCs were analyzed in ZF. Engraftment of CSCs induced faster metastatic onset, however after six days both cell subpopulations equally responded to the ZF microenvironment, resulting in the same increase of stemness genes expression including Nanog, Oct-4 and Cripto. Knockdown of Cripto significantly reduced the vimentin/E-cadherin ratio in engrafted cells, indicating that Cripto is required for transduction of the microenvironment signals from the ZF niche to increase mesenchymal potential of cells. Targeting of either Cripto or EMT transcriptional factors Snail 1 and Zeb1 significantly suppressed metastatic growth. These data indicated that zebrafish microenvironment governed the CSC/EMT plasticity of human PCa cells promoting metastasis initiation.


2004 ◽  
Vol 200 (7) ◽  
pp. 847-856 ◽  
Author(s):  
Mark J. Miller ◽  
Olga Safrina ◽  
Ian Parker ◽  
Michael D. Cahalan

The adaptive immune response is initiated in secondary lymphoid organs by contact between antigen-bearing dendritic cells (DCs) and antigen-specific CD4+ T cells. However, there is scant information regarding the single cell dynamics of this process in vivo. Using two-photon microscopy, we imaged the real-time behavior of naive CD4+ T cells and in vivo–labeled DCs in lymph nodes during a robust T cell response. In the first 2 h after entry into lymph nodes, T cells made short-lived contacts with antigen-bearing DCs, each contact lasting an average of 11–12 min and occurring mainly on dendrites. Altered patterns of T cell motility during this early stage of antigen recognition promoted serial engagement with several adjacent DCs. Subsequently, T cell behavior progressed through additional distinct stages, including long-lived clusters, dynamic swarms, and finally autonomous migration punctuated by cell division. These observations suggest that the immunological synapse in native tissues is remarkably fluid, and that stable synapses form only at specific stages of antigen presentation to T cells. Furthermore, the serial nature of these interactions implies that T cells activate by way of multiple antigen recognition events.


2021 ◽  
Vol 118 (6) ◽  
pp. e2023888118
Author(s):  
Feifei Wang ◽  
Zhuoran Ma ◽  
Yeteng Zhong ◽  
Felix Salazar ◽  
Chun Xu ◽  
...  

Noninvasive optical imaging with deep tissue penetration depth and high spatiotemporal resolution is important to longitudinally studying the biology at the single-cell level in live mammals, but has been challenging due to light scattering. Here, we developed near-infrared II (NIR-II) (1,000 to 1,700 nm) structured-illumination light-sheet microscopy (NIR-II SIM) with ultralong excitation and emission wavelengths up to ∼1,540 and ∼1,700 nm, respectively, suppressing light scattering to afford large volumetric three-dimensional (3D) imaging of tissues with deep-axial penetration depths. Integrating structured illumination into NIR-II light-sheet microscopy further diminished background and improved spatial resolution by approximately twofold. In vivo oblique NIR-II SIM was performed noninvasively for 3D volumetric multiplexed molecular imaging of the CT26 tumor microenvironment in mice, longitudinally mapping out CD4, CD8, and OX40 at the single-cell level in response to immunotherapy by cytosine-phosphate-guanine (CpG), a Toll-like receptor 9 (TLR-9) agonist combined with OX40 antibody treatment. NIR-II SIM affords an additional tool for noninvasive volumetric molecular imaging of immune cells in live mammals.


Author(s):  
Tatiana Solovieva ◽  
Hui-Chun Lu ◽  
Adam Moverley ◽  
Nicolas Plachta ◽  
Claudio D. Stern

In warm-blooded vertebrate embryos (mammals and birds), the body forms from a growth zone at the tail end. Hensen’s node, a region which induces and patterns the neural axis is located within this growth zone. The node also contains the precursors of neural, mesodermal and endodermal structures along the midline and has been suggested to contain a small population of resident stem cells. However, it is unknown whether the rest of the node constitutes an instructive stem cell niche, specifying stem cell behaviour. Here we combine transplantation of a single cell in vivo with single-cell mRNA sequencing in the chick and show that when made to enter the node, non-node-progenitor cells become resident and gain stem cell behaviour. These cells preferentially express G2/M phase cell-cycle related genes and are concentrated in posterior sub-regions of the node. The posterior part of the node therefore behaves as an instructive stem cell niche. These results demonstrate a new function for the vertebrate node during development.


2019 ◽  
Author(s):  
Shreyansh Jain ◽  
Victoire M.L. Cachoux ◽  
Gautham H.N.S. Narayana ◽  
Simon de Beco ◽  
Joseph D’Alessandro ◽  
...  

The directed migration of cell collectives is essential in various physiological processes, such as epiboly, intestinal epithelial turnover, and convergent extension during morphogenesis as well as during pathological events like wound healing and cancer metastasis1,2. Collective cell migration leads to the emergence of coordinated movements over multiple cells. Our current understanding emphasizes that these movements are mainly driven by large-scale transmission of signals through adherens junctions3,4. In this study, we show that collective movements of epithelial cells can be triggered by polarity signals at the single cell level through the establishment of coordinated lamellipodial protrusions. We designed a minimalistic model system to generate one-dimensional epithelial trains confined in ring shaped patterns that recapitulate rotational movements observed in vitro in cellular monolayers and in vivo in genitalia or follicular cell rotation5–7. Using our system, we demonstrated that cells follow coordinated rotational movements after the establishment of directed Rac1-dependent polarity over the entire monolayer. Our experimental and numerical approaches show that the maintenance of coordinated migration requires the acquisition of a front-back polarity within each single cell but does not require the maintenance of cell-cell junctions. Taken together, these unexpected findings demonstrate that collective cell dynamics in closed environments as observed in multiple in vitro and in vivo situations5,6,8,9 can arise from single cell behavior through a sustained memory of cell polarity.


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