Spatial Biology: Decoding Cellular Complexity in Tissues

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Tissues and Organs".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 2936

Special Issue Editor

Special Issue Information

Dear Colleagues,

Spatial biology (SB), also known as spatial tissue profiling, is a new and rapidly advancing discipline. Being a descendent of traditional multiplex immunohistochemistry, SB far exceeds the latter in multiplexing capacity: it allows for interrogating hundreds of genes and proteins in a single histological tissue sample, shedding light on the in situ localization of biomarkers and their interactions within the tissue microenvironment.

To mark the importance of the field of SB and address the needs of researchers to share their latest achievements, we are launching a Special Issue entitled “Spatial Biology: Decoding Cellular Complexity in Tissues”. This Special Issue will present research articles and high-quality review papers in the spatial biology/spatial tissue profiling research fields. We encourage researchers working in proteomics and transcriptomics, as well as other cell and tissue research areas, to make contributions to this Special Issue.

Dr. Alexander E. Kalyuzhny
Guest Editor

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Keywords

  • spatial biology
  • spatial tissue profiling
  • proteomics
  • transcriptomics
  • cell and tissue

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Published Papers (2 papers)

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Research

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14 pages, 37937 KB  
Communication
Unlocking the Tumor Microenvironment: Innovations in Multiplex Immunohistochemistry
by Bipin Gupta, George Yang and Marc Key
Cells 2025, 14(22), 1819; https://doi.org/10.3390/cells14221819 - 20 Nov 2025
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Abstract
The immune control of cancer growth is an area of active investigation. In this study, we demonstrated the feasibility of using standard immunohistochemistry methods in conjunction with a set of newly developed chromogens to demonstrate immune cell markers in a multiplex staining system. [...] Read more.
The immune control of cancer growth is an area of active investigation. In this study, we demonstrated the feasibility of using standard immunohistochemistry methods in conjunction with a set of newly developed chromogens to demonstrate immune cell markers in a multiplex staining system. Immune infiltrating cells in breast cancer were identified using antibodies to CD20 (B-cells), CD3 (T-cells), and CD163 (macrophages). Additionally, the tumor compartment was identified using cytokeratin (AE1/AE3), and Ki67 was used to determine the proliferation index. These stains showed a significant immune cell infiltrate surrounding and within the tumors. B-cells, T-cells, and macrophages were abundant at the tumor periphery, particularly in areas where tertiary lymphoid structures were also present. In contrast, B-cells were significantly reduced within the tumor interior compared to an abundant infiltrate of T-cells and macrophages. Patterns of B-cell, T-cell, and macrophage infiltration were identified. Depending upon the particular set of markers chosen for analysis, a simple visual examination, without the aid of computer-assisted imaging systems, was sufficient to differentiate up to five different markers. Full article
(This article belongs to the Special Issue Spatial Biology: Decoding Cellular Complexity in Tissues)
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Other

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15 pages, 595 KB  
Perspective
Spatial Biology Evolution: Past, Present and Future of Mapping Life in Context
by Alexander E. Kalyuzhny
Cells 2026, 15(9), 743; https://doi.org/10.3390/cells15090743 - 22 Apr 2026
Viewed by 633
Abstract
The life sciences are currently undergoing a serious transition from the reductive biochemical analysis of dissociated tissues to non-destructive “spatial forensics”. In addition to discovering new molecules, we are moving towards finding out their precise tissue localization and performing in situ interrogation to [...] Read more.
The life sciences are currently undergoing a serious transition from the reductive biochemical analysis of dissociated tissues to non-destructive “spatial forensics”. In addition to discovering new molecules, we are moving towards finding out their precise tissue localization and performing in situ interrogation to uncover a biological logic within preserved cellular “neighborhoods”. Our perspective is focused on exploring the spatial imperative, including the structural logic and “neighborhood effects” of the tissue microenvironment, which is a prerequisite to understanding cellular function in normal and in pathological conditions. Beginning with a historical foundation of the origins of histochemistry, dating back to the 19th century with pioneer botanist François-Vincent Raspail, we emphasize the technological metamorphosis, transitioning from classical immunohistochemistry to modern multi- and high-plex spatial multi-omics. A critical evaluation of the current operational landscape has been made, addressing the engineering strategies behind multiplexed immunofluorescence (mIF), the challenges of experimental design in spatial transcriptomics, and the functional symbiosis between targeted and unbiased spatial proteomics. There are many layers of genomic and proteomic information we have to consider in order to unravel the mechanisms underlying body function. If we learn how to combine all this information together, we will be able to better understand how cells communicate with each other and what disrupts their communication, leading to cancer and many other pathologies. It is obvious that by implementing spatial biology tools, it becomes possible to develop new medicines and treat diseases in the most efficient ways. At the same time, we realize that there is an urgent need to learn how to put data pieces together so that they blend seamlessly into a meaningful output, further transitioning spatial biology over time into a routine tool to cure for both common and rare diseases and improve our lives and health. Full article
(This article belongs to the Special Issue Spatial Biology: Decoding Cellular Complexity in Tissues)
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