Single cell analysis reveals a biophysical aspect of collective cell-state transition in embryonic stem cell differentiation

In many phenomena of biological systems, not a majority, but a minority of cells act on the entire multicellular system causing drastic changes in the system properties. To understand the mechanisms underlying such phenomena, it is essential to observe the spatiotemporal dynamics of a huge population of cells at sub-cellular resolution, which is difficult with conventional tools such as microscopy and flow cytometry. Here, we describe an imaging system named AMATERAS that enables optical imaging with an over-one-centimeter field-of-view and a-few-micrometer spatial resolution. This trans-scale-scope has a simple configuration, composed of a low-power lens for machine vision and a hundred-megapixel image sensor. We demonstrated its high cell-throughput, capable of simultaneously observing more than one million cells. We applied it to dynamic imaging of calcium ions in HeLa cells and cyclic-adenosine-monophosphate in Dictyostelium discoideum, and successfully detected less than 0.01% of rare cells and observed multicellular events induced by these cells.

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Section: Discussionmentioning

confidence: 99%

Exploring Rare Cellular Activity in More Than One Million Cells by a Trans-scale- Scope

Ichimura

Kakizuka

Horikawa

et al. 2021

Preprint

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“…43,44 In contrast, our imaging system has the potential to be the next-generation tool for imaging cytometry with a throughput of >10 5 cells in a single shot. Moreover, AMATERAS1.0 can perform time-lapse cytometry for dynamic transition of cellular state in a multi-cellular system, 45 which is impossible by means of the flow cytometry. As a possibility for further development, combining MERFISH (multiplexed error-robust fluorescence hybridization), which is known as a transcriptome method under imaging, 46 is promising to maximize the advantage of image cytometry.…”

Section: Discussionmentioning

confidence: 99%

Exploring rare cellular activity in more than one million cells by a trans-scale-scope

Ichimura

Kakizuka

Horikawa

et al. 2020

Preprint

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AbstractThere are many phenomena in biological systems where less than 1% of rare cells trigger entire multicellular systems. In order to scientifically understand the mechanisms of these rare cell-driven systems, simultaneous observation of huge populations of cells is essential. It has been difficult to observe the dynamics of such phenomena with conventional microscopes. In this study, we propose a novel type of imager, trans-scale-scope, which allows us to observe cell dynamics with sub-cell resolution in a field of view greater than a centimeter. The imaging system is mainly composed of a hundred-megapixel image sensor and a macro-lens for full-size sensor. This method, which is the basement of the future imaging system named AMATERAS (A Multi-scale/modal Analytical Tool for Every Rare Activity in Singularity), realized observation of sub-million cells at the same time. By observing the macroscale-pattern formation process of Dictyostelium discoideum, a model organism for studying fundamental aspects of cell-cell communication and chemotaxis, we have shown that the 0.1 % of rare cells triggered a stream of collective cell migration.

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“…After division, when cells exit the central domain, they lose their ability to fluctuate to other states, whereas the cell which remains in the central domain can still fluctuate between all the cell states ( Figure 1B ). State fluctuation represents a way of creating cellular heterogeneity within animal embryonic stem cells ( Okamoto et al, 2018 ; Huang et al, 2020 ) and noise in gene activity is often important for promoting cell fate transitions ( Eldar and Elowitz, 2010 ), making the second scenario worth considering in the CSC context.…”

Section: Two Scenarios For Cell Fate Decisions Of Cambium Stem Cell D...mentioning

confidence: 99%

Cell Fate Decisions Within the Vascular Cambium–Initiating Wood and Bast Formation

2022

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Precise coordination of cell fate decisions is a hallmark of multicellular organisms. Especially in tissues with non-stereotypic anatomies, dynamic communication between developing cells is vital for ensuring functional tissue organization. Radial plant growth is driven by a plant stem cell niche known as vascular cambium, usually strictly producing secondary xylem (wood) inward and secondary phloem (bast) outward, two important structures serving as much-needed CO2 depositories and building materials. Because of its bidirectional nature and its developmental plasticity, the vascular cambium serves as an instructive paradigm for investigating principles of tissue patterning. Although genes and hormones involved in xylem and phloem formation have been identified, we have a yet incomplete picture of the initial steps of cell fate transitions of stem cell daughters into xylem and phloem progenitors. In this mini-review perspective, we describe two possible scenarios of cell fate decisions based on the current knowledge about gene regulatory networks and how cellular environments are established. In addition, we point out further possible research directions.

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Single cell analysis reveals a biophysical aspect of collective cell-state transition in embryonic stem cell differentiation

Cited by 15 publications

References 63 publications

Exploring Rare Cellular Activity in More Than One Million Cells by a Trans-scale- Scope

Exploring Rare Cellular Activity in More Than One Million Cells by a Trans-scale- Scope

Exploring rare cellular activity in more than one million cells by a trans-scale-scope

Cell Fate Decisions Within the Vascular Cambium–Initiating Wood and Bast Formation

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