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Complementing cell taxonomies with a multicellular functional analysis of tissues (2403.06753v1)

Published 11 Mar 2024 in q-bio.TO and q-bio.CB

Abstract: The application of single-cell molecular profiling coupled with spatial technologies has enabled charting cellular heterogeneity in reference tissues and in disease. This new wave of molecular data has highlighted the expected diversity of single-cell dynamics upon shared external queues and spatial organizations. However, little is known about the relationship between single cell heterogeneity and the emergence and maintenance of robust multicellular processes in developed tissues and its role in (patho)physiology. Here, we present emerging computational modeling strategies that use increasingly available large-scale cross-condition single cell and spatial datasets, to study multicellular organization in tissues and complement cell taxonomies. This perspective should enable us to better understand how cells within tissues collectively process information and adapt synchronized responses in disease contexts and to bridge the gap between structural changes and functions in tissues.

Citations (2)

Summary

  • The paper presents a novel computational framework linking single-cell profiles with tissue-level multicellular coordination.
  • It demonstrates that traditional cell taxonomies can be enhanced by analyzing intercellular dependencies and collective tissue functionalities.
  • The study paves the way for precise meta-analysis and therapeutic targeting by revealing emergent multicellular networks.

Multicellular Analysis for Tissue Function Understanding

The integration of single-cell molecular profiling with spatial technologies has catalyzed a more comprehensive exploration of cellular diversity within tissues, underscoring their heterogeneity in normal and diseased states. The paper under discussion, "Complementing cell taxonomies with a multicellular functional analysis of tissues," introduces emerging computational modeling strategies that utilize extensive single-cell and spatial datasets across conditions to better understand multicellular organization. The objective is to move beyond cell-type taxonomies and focus on the multicellular coordination necessary for physiological functions, thereby addressing the gap between cellular diversity and the emergence of collective tissue functions.

Cell Cooperation and Tissue Function

The paper begins by emphasizing that understanding tissue function requires exploring not only the variety of cells in the human body and their spatial organization but also their multicellular coordination. While initiatives such as the Human Cell Atlas and the Human Biomolecular Atlas Program have made advances in charting human cellular diversity, there remains a need to contextualize these findings within the functional framework of tissue physiology. The paper argues that the current understanding of tissue function based on cell taxonomy may be limited without considering the interdependent role of cell cooperation.

Multicellular Coordination: From Data to Function

The authors highlight the inherent challenges of inferring multicellular processes from existing data. Emerging approaches focus on a tissue-centric analysis of single cells, aiming to infer high-level representations of multicellular responses and decompose them into specific cell-cell dependencies. This shift from individual cellular behaviors to tissue function analysis is posited to clarify the coordination between cells and bolster the understanding of cellular diversity as a mechanism to ensure collective function. The paper reviews emerging strategies for leveraging single-cell data to paper multicellular coordination and recognize the functional relevance of specific cell groups within multicellular processes.

Limitations of Current Taxonomies

A critical analysis of current cell taxonomies is provided, outlining their inability to fully capture the continuous nature of biological functions. The paper argues that classifications based on discrete taxonomies fall short of explaining tissue functions, often overlooking the functional diversity within cell groups. By drawing attention to the misconnection between taxonomic categories and cellular function, it asserts the need for integrating cellular relationship data into the taxonomic framework.

Methodological Advances and Theoretical Implications

From the theoretical perspective, multicellular coordination is an emergent property of cellular dependencies, with implications extending from development to disease. The paper examines several experimental demonstrations of multicellular coordination, such as information processing in multicellular systems, and proposes a top-down approach to infer multicellular information networks. This is achieved through integrating tissue composition, organization, and coordination, positing that these networks are foundational for understanding physiopathological processes.

Future Directions and Impact

The implications of adopting a multicellular functional perspective on single-cell data are manifold. By integrating the descriptions of tissue composition and organization with functional dependencies, researchers can enhance the understanding of tissue functions. This perspective is projected to drive the development of novel strategies that blend insights from mathematical physiology, ecology, and systems biology. Practically, it presents opportunities for more precise meta-analysis of disease processes and patient cohorts, potentially facilitating the discovery of therapeutic interventions targeting multicellular coordination disruptions.

Conclusion

The paper convincingly posits that to understand tissue function comprehensively, it is imperative to paper how cells coherently integrate their intra- and extracellular processes amid single-cell heterogeneity. Multicellular network descriptions could grant more functional insights into tissues, aligning single-cell atlas findings with meaningful physiological processes. This expanded viewpoint may catalyze a shift in developing therapeutics by broadening the focus from isolated cellular activities to the orchestration of cellular communities. The proposed framework could therefore serve as a critical stepping stone toward a deeper understanding of human biologics and pathophysiology.

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