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Functional tissue units and their primary tissue motifs in multi-scale physiology.

de Bono B, Grenon P, Baldock R, Hunter P - J Biomed Semantics (2013)

Bottom Line: These approaches have not significantly facilitated the general integration of tissue- and molecular-level knowledge across the board in support of a systematic classification of tissue function, as well as the coherent multi-scale study of physiology.In our work, we outline the biophysical rationale for a rigorous definition of a unit of functional tissue organization, and demonstrate the application of primary motifs in tissue classification.In so doing, we acknowledge (i) the fundamental role of capillaries in directing and radically informing tissue architecture, as well as (ii) the importance of taking into full account the critical influence of neighbouring cellular environments when studying complex developmental and pathological phenomena.

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Affiliation: Auckland Bioengineering Institute, University of Auckland, Symonds Street, Auckland 1010, New Zealand. b.bono@ucl.ac.uk.

ABSTRACT

Background: Histology information management relies on complex knowledge derived from morphological tissue analyses. These approaches have not significantly facilitated the general integration of tissue- and molecular-level knowledge across the board in support of a systematic classification of tissue function, as well as the coherent multi-scale study of physiology. Our work aims to support directly these integrative goals.

Results: We describe, for the first time, the precise biophysical and topological characteristics of functional units of tissue. Such a unit consists of a three-dimensional block of cells centred around a capillary, such that each cell in this block is within diffusion distance from any other cell in the same block. We refer to this block as a functional tissue unit. As a means of simplifying the knowledge representation of this unit, and rendering this knowledge more amenable to automated reasoning and classification, we developed a simple descriptor of its cellular content and anatomical location, which we refer to as a primary tissue motif. In particular, a primary motif captures the set of cellular participants of diffusion-mediated interactions brokered by secreted products to create a tissue-level molecular network.

Conclusions: Multi-organ communication, therefore, may be interpreted in terms of interactions between molecular networks housed by interconnected functional tissue units. By extension, a functional picture of an organ, or its tissue components, may be rationally assembled using a collection of these functional tissue units as building blocks. In our work, we outline the biophysical rationale for a rigorous definition of a unit of functional tissue organization, and demonstrate the application of primary motifs in tissue classification. In so doing, we acknowledge (i) the fundamental role of capillaries in directing and radically informing tissue architecture, as well as (ii) the importance of taking into full account the critical influence of neighbouring cellular environments when studying complex developmental and pathological phenomena.

No MeSH data available.


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Example workflow illustrating the acquisition and processing of FTU data from a three-dimensional reconstruction of human colon tissue. Step 1: The FTU template (A) is prepared according to the biophysical constraints under consideration, such that the long axis of the resulting cylindrical block of tissue is that of the feeding capillary (CAP) on which it is metabolically dependent. This template is applied to an appropriate volumetric region in the three-dimensional histology image dataset (B). The various cells within this region (coloured boxes) are typed and their position recorded (Note: red boxes represent endothelial cells, here shown lining the feeding capillary – CAP – and the erythrocytes within its lumen). Step 2: The cellular annotations across the full extent of the FTU cylindrical boundaries (C) are stored, together with the image data and the anatomical provenance of the tissue sample. Step 3: As the resulting primary tissue motif for the above colonic FTU uses standard reference ontology terms to represent both (i) a non-redundant list of distinct cell types, as well as (ii) the anatomical region of origin for the sourced tissue material, a terse graphical depiction of the constitution of this FTU may be automatically included in the context of whole-body anatomy maps, such as the one schematized by the ApiNATOMY tool[9] in (D). In this schematic, the outer boundary of the map represents the various epithelial surface categories (each individually coloured and labelled), and the inside tiles represent vascular (red) and neural (purple) structures respectively.
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Figure 1: Example workflow illustrating the acquisition and processing of FTU data from a three-dimensional reconstruction of human colon tissue. Step 1: The FTU template (A) is prepared according to the biophysical constraints under consideration, such that the long axis of the resulting cylindrical block of tissue is that of the feeding capillary (CAP) on which it is metabolically dependent. This template is applied to an appropriate volumetric region in the three-dimensional histology image dataset (B). The various cells within this region (coloured boxes) are typed and their position recorded (Note: red boxes represent endothelial cells, here shown lining the feeding capillary – CAP – and the erythrocytes within its lumen). Step 2: The cellular annotations across the full extent of the FTU cylindrical boundaries (C) are stored, together with the image data and the anatomical provenance of the tissue sample. Step 3: As the resulting primary tissue motif for the above colonic FTU uses standard reference ontology terms to represent both (i) a non-redundant list of distinct cell types, as well as (ii) the anatomical region of origin for the sourced tissue material, a terse graphical depiction of the constitution of this FTU may be automatically included in the context of whole-body anatomy maps, such as the one schematized by the ApiNATOMY tool[9] in (D). In this schematic, the outer boundary of the map represents the various epithelial surface categories (each individually coloured and labelled), and the inside tiles represent vascular (red) and neural (purple) structures respectively.

Mentions: It is therefore possible to identify a unit of solid tissue consisting of a well-defined heterogeneous set of cells that is both (i) metabolically dependent on the same capillary, as well as (ii) the cellular substrate for tissue-level molecular pathways co-ordinated via paracrine communication. This block of tissue has a cylindrical shape whose long axis is that of the feeding capillary on which it is metabolically dependent (Figure 1A). The rigid biophysical constraint that within this cylinder no two cells may be more than 100 μm apart (dashed line, Figure 1A) provides a fundamental mathematical limit to calculate the absolute dimensions of an FTU. As the application of this limit in isolation gives rise to multiple solutions, the addition of a second constraint is required to provide specific values to the diameter and length of a cylindrical tissue block. For instance, by requiring that the particular cylinder of choice is one that achieves the maximal volume (i.e. the volume ensuring the greatest possible mass of protein metabolic machinery within the FTU substrate) we have estimated the diameter of that cylindrical block to be about 80 μm and the length approximately 60 μm.


Functional tissue units and their primary tissue motifs in multi-scale physiology.

de Bono B, Grenon P, Baldock R, Hunter P - J Biomed Semantics (2013)

Example workflow illustrating the acquisition and processing of FTU data from a three-dimensional reconstruction of human colon tissue. Step 1: The FTU template (A) is prepared according to the biophysical constraints under consideration, such that the long axis of the resulting cylindrical block of tissue is that of the feeding capillary (CAP) on which it is metabolically dependent. This template is applied to an appropriate volumetric region in the three-dimensional histology image dataset (B). The various cells within this region (coloured boxes) are typed and their position recorded (Note: red boxes represent endothelial cells, here shown lining the feeding capillary – CAP – and the erythrocytes within its lumen). Step 2: The cellular annotations across the full extent of the FTU cylindrical boundaries (C) are stored, together with the image data and the anatomical provenance of the tissue sample. Step 3: As the resulting primary tissue motif for the above colonic FTU uses standard reference ontology terms to represent both (i) a non-redundant list of distinct cell types, as well as (ii) the anatomical region of origin for the sourced tissue material, a terse graphical depiction of the constitution of this FTU may be automatically included in the context of whole-body anatomy maps, such as the one schematized by the ApiNATOMY tool[9] in (D). In this schematic, the outer boundary of the map represents the various epithelial surface categories (each individually coloured and labelled), and the inside tiles represent vascular (red) and neural (purple) structures respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 1: Example workflow illustrating the acquisition and processing of FTU data from a three-dimensional reconstruction of human colon tissue. Step 1: The FTU template (A) is prepared according to the biophysical constraints under consideration, such that the long axis of the resulting cylindrical block of tissue is that of the feeding capillary (CAP) on which it is metabolically dependent. This template is applied to an appropriate volumetric region in the three-dimensional histology image dataset (B). The various cells within this region (coloured boxes) are typed and their position recorded (Note: red boxes represent endothelial cells, here shown lining the feeding capillary – CAP – and the erythrocytes within its lumen). Step 2: The cellular annotations across the full extent of the FTU cylindrical boundaries (C) are stored, together with the image data and the anatomical provenance of the tissue sample. Step 3: As the resulting primary tissue motif for the above colonic FTU uses standard reference ontology terms to represent both (i) a non-redundant list of distinct cell types, as well as (ii) the anatomical region of origin for the sourced tissue material, a terse graphical depiction of the constitution of this FTU may be automatically included in the context of whole-body anatomy maps, such as the one schematized by the ApiNATOMY tool[9] in (D). In this schematic, the outer boundary of the map represents the various epithelial surface categories (each individually coloured and labelled), and the inside tiles represent vascular (red) and neural (purple) structures respectively.
Mentions: It is therefore possible to identify a unit of solid tissue consisting of a well-defined heterogeneous set of cells that is both (i) metabolically dependent on the same capillary, as well as (ii) the cellular substrate for tissue-level molecular pathways co-ordinated via paracrine communication. This block of tissue has a cylindrical shape whose long axis is that of the feeding capillary on which it is metabolically dependent (Figure 1A). The rigid biophysical constraint that within this cylinder no two cells may be more than 100 μm apart (dashed line, Figure 1A) provides a fundamental mathematical limit to calculate the absolute dimensions of an FTU. As the application of this limit in isolation gives rise to multiple solutions, the addition of a second constraint is required to provide specific values to the diameter and length of a cylindrical tissue block. For instance, by requiring that the particular cylinder of choice is one that achieves the maximal volume (i.e. the volume ensuring the greatest possible mass of protein metabolic machinery within the FTU substrate) we have estimated the diameter of that cylindrical block to be about 80 μm and the length approximately 60 μm.

Bottom Line: These approaches have not significantly facilitated the general integration of tissue- and molecular-level knowledge across the board in support of a systematic classification of tissue function, as well as the coherent multi-scale study of physiology.In our work, we outline the biophysical rationale for a rigorous definition of a unit of functional tissue organization, and demonstrate the application of primary motifs in tissue classification.In so doing, we acknowledge (i) the fundamental role of capillaries in directing and radically informing tissue architecture, as well as (ii) the importance of taking into full account the critical influence of neighbouring cellular environments when studying complex developmental and pathological phenomena.

View Article: PubMed Central - HTML - PubMed

Affiliation: Auckland Bioengineering Institute, University of Auckland, Symonds Street, Auckland 1010, New Zealand. b.bono@ucl.ac.uk.

ABSTRACT

Background: Histology information management relies on complex knowledge derived from morphological tissue analyses. These approaches have not significantly facilitated the general integration of tissue- and molecular-level knowledge across the board in support of a systematic classification of tissue function, as well as the coherent multi-scale study of physiology. Our work aims to support directly these integrative goals.

Results: We describe, for the first time, the precise biophysical and topological characteristics of functional units of tissue. Such a unit consists of a three-dimensional block of cells centred around a capillary, such that each cell in this block is within diffusion distance from any other cell in the same block. We refer to this block as a functional tissue unit. As a means of simplifying the knowledge representation of this unit, and rendering this knowledge more amenable to automated reasoning and classification, we developed a simple descriptor of its cellular content and anatomical location, which we refer to as a primary tissue motif. In particular, a primary motif captures the set of cellular participants of diffusion-mediated interactions brokered by secreted products to create a tissue-level molecular network.

Conclusions: Multi-organ communication, therefore, may be interpreted in terms of interactions between molecular networks housed by interconnected functional tissue units. By extension, a functional picture of an organ, or its tissue components, may be rationally assembled using a collection of these functional tissue units as building blocks. In our work, we outline the biophysical rationale for a rigorous definition of a unit of functional tissue organization, and demonstrate the application of primary motifs in tissue classification. In so doing, we acknowledge (i) the fundamental role of capillaries in directing and radically informing tissue architecture, as well as (ii) the importance of taking into full account the critical influence of neighbouring cellular environments when studying complex developmental and pathological phenomena.

No MeSH data available.


Related in: MedlinePlus