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Cell polarity: cell type-specific regulators, common pathways, and polarized vesicle transport

Leukemia volume 39, pages 1558–1570 (2025)Cite this article

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Abstract

Cell polarity, the asymmetric organization of cellular components, is evolutionarily conserved from unicellular and multicellular organisms and is crucial for many biological processes. Polarity is required to maintain cell and tissue integrity by regulating cell division, migration, orientation, cell-cell interactions, and morphogenesis. Impaired polarity leads to dysregulation of cellular functions and is associated with disease. Understanding how polarity is established, maintained, and regulated is thus critical to improving our knowledge of pathologies and devising novel therapies. Here, we explore the various manifestations of cell polarity across different model systems, tissues, and cell types and focus on known polarity mechanisms in hematopoietic stem and progenitor cells. We discuss how cells with vastly different functions utilize conserved molecular complexes to establish cell polarity while adapting polarity proteins to unique cell-type-specific functions. In this discussion, we attempt to extract common themes and concepts to improve our understanding of cell polarity in hematological malignancies and other diseases. Finally, we summarize, compare, and evaluate classical as well as recently developed methods to quantify cell polarity, highlight important advances in imaging and analytical techniques, and suggest critical next steps required to move the field forward.

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Fig. 1: Key cell polarity mechanisms across different cell types.
Fig. 2: Mechanisms of cell polarity in fission and budding yeast.
Fig. 3: Microtubule and actin-mediated vesicle transport establishes and maintains apical-basal polarity in epithelial cells.
Fig. 4: Polarized vesicular transport sustains polarity and signaling at the Immunological Synapse.
Fig. 5: Loss of CDC42 polarity in aged HSCs correlates with functional decline.
Fig. 6: Asymmetric Cell Division of HSCs is regulated by the asymmetric segregation of endolysosomal vesicles during division.
Fig. 7: Comparison of available methods to quantify cell polarity.

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Funding

Research reported in this publication was supported by the National Heart, Lung, And Blood Institute (NHLBI) of the National Institutes of Health (NIH) under Award Number R01HL174644. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional funding was received from Alex’s Lemonade Stand Foundation and RUNX1 Research Program (Grant # 22-27080) and St. Jude Comprehensive Cancer Center Developmental Funds Grant (#PROJ-0003066 720202211).

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Authors and Affiliations

  1. Department of Hematology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Soumen Bera & Dirk Loeffler

  2. Comprehensive Cancer Center, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Soumen Bera & Dirk Loeffler

  3. Department of Pathology and Laboratory Medicine, The University of Tennessee, Memphis, TN, USA

    Soumen Bera & Dirk Loeffler

Authors
  1. Soumen Bera
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  2. Dirk Loeffler
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D.L. and S.B. wrote, edited, and reviewed the manuscript.

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Correspondence to Dirk Loeffler.

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Bera, S., Loeffler, D. Cell polarity: cell type-specific regulators, common pathways, and polarized vesicle transport. Leukemia 39, 1558–1570 (2025). https://doi.org/10.1038/s41375-025-02601-x

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