Spatial biology is the study of biomolecules and cells in their native three-dimensional context. Spatial biology encompasses different levels of cellular resolution including (1)

subcellular localization The cells of eukaryotic organisms are elaborately subdivided into functionally-distinct membrane-bound compartments. Some major constituents of eukaryotic cells are: extracellular space, plasma membrane, cytoplasm, nucleus, mitochondria, Golgi a ...

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...

, and

proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...

, (2) single-cell resolution and ''

in situ is a Latin phrase meaning 'in place' or 'on site', derived from ' ('in') and ' ( ablative of ''situs'', ). The term typically refers to the examination or occurrence of a process within its original context, without relocation. The term is use ...

'' communications like cell-cell interactions and

cell signaling In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...

, (3) cellular neighborhoods, regions, or microenvironments, and (4) tissue architecture and organization in

organs In a multicellular organism, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to a ...

. Dysregulation of tissue organization is a common feature in human disease progression including

tumorigenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abn ...

and

neurodegeneration A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their cell death, death. Neurodegenerative diseases include amyotrophic lateral sc ...

. Many fields within biology are studied for their individual contribution to spatial biology.

Spatial transcriptomics

Spatial transcriptomics measures

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

transcript abundance and distribution ''

'' across a tissue. Spatial method for RNA ''in situ'' detection is first described in a 1969 landmark paper by Joseph G. Gall and Mary-Lou Pardue. Previous to spatial transcriptomics techniques, whole transcriptome profiling lacked spatial context because tissues were ground up in bulk RNA-seq or dissociated into single cells suspensions in single cell RNA-seq. Although some literature refers to "spatial genomics" for RNA, growing consensus has settled on usage of "spatial transcriptomics" or "spatially resolved transcriptomics."

Spatial proteomics

Spatial

proteomics Proteomics is the large-scale study of proteins. Proteins are vital macromolecules of all living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replicatio ...

measures the localization and abundance of proteins at the subcellular level across a tissue.

Immunohistochemistry Immunohistochemistry is a form of immunostaining. It involves the process of selectively identifying antigens in cells and tissue, by exploiting the principle of Antibody, antibodies binding specifically to antigens in biological tissues. Alber ...

-based spatial proteomic methods include oligo barcoded antibodies, cyclic immunofluorescence (cycIF), co-detection by indexing (CODEX), iterative bleaching extends multiplicity (IBEX), multiplexed ion beam imaging (MIBI) and imaging mass cytometry (IMC). Other methods includes deep visual proteomics that profile protein expression in single cells by

laser capture microdissection Laser capture microdissection (LCM), also called microdissection, laser microdissection (LMD), or laser-assisted microdissection (LMD or LAM), is a method for isolating specific cells of interest from microscopic regions of tissue/cells/organisms ...

and

mass spectroscopy Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is used ...

. The term "spatial medicine" is recently coined by

Eric Topol Eric Jeffrey Topol (born June 26, 1954) is an American cardiologist, scientist, and author. He is the founder and director of the Scripps Research Translational Institute, a professor of Molecular Medicine and Executive Vice-President at Scripp ...

to refer to a study that used deep visual proteomics to find a therapeutic treatment for patients with a rare skin condition.

Spatial genomics

Spatial genomics localizes the native three dimensional genome architecture within the nucleus.

Nuclear organization Nuclear organization refers to the spatial organization and dynamics of chromatin within a cell nucleus during interphase. There are many different levels and scales of nuclear organization. At the smallest scale, DNA is packaged into ...

of chromosomes and how chromosomes are positioned and folded has implications for

gene regulation Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are wide ...

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, often th ...

DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all life, living organisms, acting as the most essential part of heredity, biolog ...

DNA damage repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is constantly modified ...

, and

cell division Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...

Spatial omics vs Spatial Biology

Spatial omics refers to the collection of high-throughput molecular profiling techniques that measure and spatially map the distribution of transcriptome, proteome or other biomolecules in a tissue. Spatial biology is a more general term that encompasses the science and techniques, but often spatial biology and spatial omics are used interchangeably.

References

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