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36. Evidence that a lipolytic enzyme—hematopoietic-specific phospholipase C-β2—promotes mobilization of hematopoietic stem cells by decreasing their lipid raft-mediated bone marrow retention and increasing the promobilizing effects of granulocytes

Author

Adamiak, M, primary, Poniewierska-Baran, A, additional, Borkowska, S, additional, Schneider, G, additional, Abdelbaset-Ismail, A, additional, Suszynska, M, additional, Abdel-Latif, A, additional, Kucia, M, additional, Ratajczak, J, additional, and Ratajczak, M Z, additional

Published
2015
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46. Leukemogenesis occurs in a microenvironment enriched by extracellular microvesicles/exosomes: recent discoveries and questions to be answered.

Author

Ratajczak MZ and Ratajczak J

Subjects
Humans, Cell Communication, Signal Transduction, Proteins metabolism, Exosomes metabolism, Cell-Derived Microparticles, Extracellular Vesicles metabolism
Abstract

In single-cell organisms, extracellular microvesicles (ExMVs) were one of the first cell-cell communication platforms that emerged very early during evolution. Multicellular organisms subsequently adapted this mechanism. Evidence indicates that all types of cells secrete these small circular structures surrounded by a lipid membrane that may be encrusted by ligands and receptors interacting with target cells and harboring inside a cargo comprising RNA species, proteins, bioactive lipids, signaling nucleotides, and even entire organelles "hijacked" from the cells of origin. ExMVs are secreted by normal cells and at higher levels by malignant cells, and there are some differences in their cargo. On the one hand, ExMVs secreted from malignant cells interact with cells in the microenvironment, and in return, they are exposed by a "two-way mechanism" to ExMVs secreted by non-leukemic cells. Therefore, leukemogenesis occurs and progresses in ExMVs enriched microenvironments, and this biological fact has pathologic, diagnostic, and therapeutic implications. We are still trying to decipher this intriguing cell-cell communication language better. We will present a current point of view on this topic and review some selected most recent discoveries and papers., (© 2024. The Author(s).)

Published
2024
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48. Intracellular complement (complosome) is expressed in hematopoietic stem/progenitor cells (HSPCs) and regulates cell trafficking, metabolism and proliferation in an intracrine Nlrp3 inflammasome-dependent manner.

Author

Ratajczak MZ, Adamiak M, Abdelbaset-Ismail A, Bujko K, Thapa A, Chumak V, Franczak S, Brzezniakiewicz-Janus K, Ratajczak J, and Kucia M

Subjects
Humans, Complement System Proteins metabolism, Cell Proliferation, Inflammasomes metabolism, Hematopoietic Stem Cells metabolism
Published
2023
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50. The P2X4 purinergic receptor has emerged as a potent regulator of hematopoietic stem/progenitor cell mobilization and homing-a novel view of P2X4 and P2X7 receptor interaction in orchestrating stem cell trafficking.

Author

Adamiak M, Bujko K, Thapa A, Pensato V, Brzezniakiewicz-Janus K, Ratajczak J, Davies DL, Ulrich H, Kucia M, and Ratajczak MZ

Subjects
Animals, Chemotaxis, Female, Granulocyte Colony-Stimulating Factor metabolism, Hematopoietic Stem Cells cytology, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, Purinergic P2X7 genetics, Signal Transduction, Hematopoietic Stem Cell Mobilization methods, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cells physiology, Receptors, Purinergic P2X4 physiology, Receptors, Purinergic P2X7 metabolism, Stem Cell Niche
Abstract

Recent evidence indicates that extracellular adenosine triphosphate (eATP), as a major mediator of purinergic signaling, plays an important role in regulating the mobilization and homing of hematopoietic stem progenitor cells (HSPCs). In our previous work we demonstrated that eATP activates the P2X7 ion channel receptor in HSPCs and that its deficiency impairs stem cell trafficking. To learn more about the role of the P2X purinergic receptor family in hematopoiesis, we phenotyped murine and human HSPCs with respect to the seven P2X receptors and observed that, these cells also highly express P2X4 receptors, which shows ~50% sequence similarity to P2X7 subtypes, but that P2X4 cells are more sensitive to eATP and signal much more rapidly. Using the selective P2X4 receptor antagonist PSB12054 as well as P2X4-KO mice, we found that the P2X4 receptor, similar to P2X7 receptor, promotes trafficking of HSPCs in that its deficiency leads to impaired chemotaxis of HSPCs in response to a stromal-derived factor 1 (SDF-1) gradient, less effective pharmacological mobilization, and defective homing and engraftment of HSPCs after transplantation into myeloablated hosts. This correlated with a decrease in SDF-1 expression in the BM microenvironment. Overall, our results confirm the proposed cooperative dependence of both receptors in response to eATP signaling. In G-CSF-induced mobilization, a lack of one receptor is not compensated by the presence of the other one, which supports their mutual dependence in regulating HSPC trafficking., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2022
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