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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.

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

Mock up of whole-body treemap schematic depicting a multi-organ endocrine pathway consiting of interlinked FTU-level molecular networks. Figure 1D is extended to depict a number of primary tissue motifs representing FTUs involved in the endocrine regulation of electrolyte and blood pressure levels during exercise. Every individual motif is labeled (in blue – see below for key to label abbreviations). In this mockup of an ApiNATOMY[9] schematic, nesting of one box within another represents the part_of relation such that: (i) tiles representing motifs are nested within tiles representing the anatomical region of origin for the tissue material from which the FTU was acquired, and (ii) tiles representing the constitutent cells of the motif are nested within the corresponding motif tile. The position of nodes in the treegraph overlaid onto the treemap depicts the location of substances (i.e. molecules or charged atoms), with respect to the motif constituents, as follows: a node within the boundary of a cell tile represents an intracellular substance; on the boundary of a cell tile represent a molecule tethered to the plasma membrane of that cell; outside all cell boundaries represents a substance located in the extracellular tissue fluid of the corresponding FTU. TISSUE MOTIF LABELS: [LGIN: Large Intestine; SMIN: Small Intestine; LIVR: Liver; STMC: Stomach; ADRC: Adrenal Cortices; HART: Heart; ARTL: Arterioles; BLOD: Blood; LUNG: Lungs; KDNY: Kidneys; ADRM: Adrenal Medullae; CORD: Spinal Cord; MEDL: Medulla Oblongata; PITR: Pituitary; SKLM: Skeletal Muscles; SWET: Sweat Glands]. EDGE COLOUR: [Black: Molecular Binding; Blue: Intercompartmental Translocation].
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Figure 3: Mock up of whole-body treemap schematic depicting a multi-organ endocrine pathway consiting of interlinked FTU-level molecular networks. Figure 1D is extended to depict a number of primary tissue motifs representing FTUs involved in the endocrine regulation of electrolyte and blood pressure levels during exercise. Every individual motif is labeled (in blue – see below for key to label abbreviations). In this mockup of an ApiNATOMY[9] schematic, nesting of one box within another represents the part_of relation such that: (i) tiles representing motifs are nested within tiles representing the anatomical region of origin for the tissue material from which the FTU was acquired, and (ii) tiles representing the constitutent cells of the motif are nested within the corresponding motif tile. The position of nodes in the treegraph overlaid onto the treemap depicts the location of substances (i.e. molecules or charged atoms), with respect to the motif constituents, as follows: a node within the boundary of a cell tile represents an intracellular substance; on the boundary of a cell tile represent a molecule tethered to the plasma membrane of that cell; outside all cell boundaries represents a substance located in the extracellular tissue fluid of the corresponding FTU. TISSUE MOTIF LABELS: [LGIN: Large Intestine; SMIN: Small Intestine; LIVR: Liver; STMC: Stomach; ADRC: Adrenal Cortices; HART: Heart; ARTL: Arterioles; BLOD: Blood; LUNG: Lungs; KDNY: Kidneys; ADRM: Adrenal Medullae; CORD: Spinal Cord; MEDL: Medulla Oblongata; PITR: Pituitary; SKLM: Skeletal Muscles; SWET: Sweat Glands]. EDGE COLOUR: [Black: Molecular Binding; Blue: Intercompartmental Translocation].

Mentions: An FTU is a unit of tissue organization where diffusive and advective flow transport modalities interlink, thus connecting molecular processes involving tissues or organs that are far apart (Figure 3). In our work, we outline the precise biophysical rationale for a rigorous definition of the FTU. In so doing, we acknowledge (i) the fundamental role of capillaries in directing and radically informing the formation of tissue architecture (e.g. as discussed in ref[24]), 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 (e.g. the effect of stromal cells on cancer progression[25]).


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)

Mock up of whole-body treemap schematic depicting a multi-organ endocrine pathway consiting of interlinked FTU-level molecular networks. Figure 1D is extended to depict a number of primary tissue motifs representing FTUs involved in the endocrine regulation of electrolyte and blood pressure levels during exercise. Every individual motif is labeled (in blue – see below for key to label abbreviations). In this mockup of an ApiNATOMY[9] schematic, nesting of one box within another represents the part_of relation such that: (i) tiles representing motifs are nested within tiles representing the anatomical region of origin for the tissue material from which the FTU was acquired, and (ii) tiles representing the constitutent cells of the motif are nested within the corresponding motif tile. The position of nodes in the treegraph overlaid onto the treemap depicts the location of substances (i.e. molecules or charged atoms), with respect to the motif constituents, as follows: a node within the boundary of a cell tile represents an intracellular substance; on the boundary of a cell tile represent a molecule tethered to the plasma membrane of that cell; outside all cell boundaries represents a substance located in the extracellular tissue fluid of the corresponding FTU. TISSUE MOTIF LABELS: [LGIN: Large Intestine; SMIN: Small Intestine; LIVR: Liver; STMC: Stomach; ADRC: Adrenal Cortices; HART: Heart; ARTL: Arterioles; BLOD: Blood; LUNG: Lungs; KDNY: Kidneys; ADRM: Adrenal Medullae; CORD: Spinal Cord; MEDL: Medulla Oblongata; PITR: Pituitary; SKLM: Skeletal Muscles; SWET: Sweat Glands]. EDGE COLOUR: [Black: Molecular Binding; Blue: Intercompartmental Translocation].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126067&req=5

Figure 3: Mock up of whole-body treemap schematic depicting a multi-organ endocrine pathway consiting of interlinked FTU-level molecular networks. Figure 1D is extended to depict a number of primary tissue motifs representing FTUs involved in the endocrine regulation of electrolyte and blood pressure levels during exercise. Every individual motif is labeled (in blue – see below for key to label abbreviations). In this mockup of an ApiNATOMY[9] schematic, nesting of one box within another represents the part_of relation such that: (i) tiles representing motifs are nested within tiles representing the anatomical region of origin for the tissue material from which the FTU was acquired, and (ii) tiles representing the constitutent cells of the motif are nested within the corresponding motif tile. The position of nodes in the treegraph overlaid onto the treemap depicts the location of substances (i.e. molecules or charged atoms), with respect to the motif constituents, as follows: a node within the boundary of a cell tile represents an intracellular substance; on the boundary of a cell tile represent a molecule tethered to the plasma membrane of that cell; outside all cell boundaries represents a substance located in the extracellular tissue fluid of the corresponding FTU. TISSUE MOTIF LABELS: [LGIN: Large Intestine; SMIN: Small Intestine; LIVR: Liver; STMC: Stomach; ADRC: Adrenal Cortices; HART: Heart; ARTL: Arterioles; BLOD: Blood; LUNG: Lungs; KDNY: Kidneys; ADRM: Adrenal Medullae; CORD: Spinal Cord; MEDL: Medulla Oblongata; PITR: Pituitary; SKLM: Skeletal Muscles; SWET: Sweat Glands]. EDGE COLOUR: [Black: Molecular Binding; Blue: Intercompartmental Translocation].
Mentions: An FTU is a unit of tissue organization where diffusive and advective flow transport modalities interlink, thus connecting molecular processes involving tissues or organs that are far apart (Figure 3). In our work, we outline the precise biophysical rationale for a rigorous definition of the FTU. In so doing, we acknowledge (i) the fundamental role of capillaries in directing and radically informing the formation of tissue architecture (e.g. as discussed in ref[24]), 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 (e.g. the effect of stromal cells on cancer progression[25]).

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