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How Methods of Molecular Biology Shape Our Understanding of the Hematopoietic System

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Abstract

Blood is extremely important for a multicellular organism: it connects all organs and tissues, supplies them with nutrients and oxygen, removes carbon dioxide and metabolic products, maintains homeostasis, and provides protection against infections. That is why studies on blood have always drawn a great deal of attention. In ancient times, it was believed that the soul was in the blood and that it sometimes “sank into the stomach.” Initially, the study of blood was limited to morphological methods, to which physiological and cellular research were added in the twentieth century. With their help, researchers established that mature blood cells are formed from a rare population of hematopoietic stem cells (HSCs), which are located in the bone marrow. The development of molecular biology methods and their combination with classical physiological ones allowed a breakthrough in understanding the structure of the hematopoietic system, which changed our understanding not only of hematopoiesis but also about the nature of adult stem cells. This review describes the molecular assays used in experimental hematology, and how their application has gradually been expanding our knowledge of blood formation and continues to provide new information about it.

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Correspondence to A. E. Bigildeev.

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The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

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Nature and nature’s laws lay hid in night; God said “Let Newton be” and all was light. (Alexander Pope, 1688–1744) It did not last; the devil howling “Ho! Let Einstein be!” restored the status quo. (Sir John Collins Squire, 1884–1958) This review is dedicated to the memory of J.L. Chertkov

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Abbreviations: HSC, hematopoietic stem cell; LT-HSC, long-term repopulating HSC (can maintain hematopoiesis for the entire life of an animal); ST-HSC, short-term repopulating HSC (can maintain hematopoiesis for 6–8 weeks); NGS, next generation sequencing; ADA, adenosine desaminase; MPP, multipotent progenitors; MyP, myeloid progenitor; CMP, common myeloid progenitor; CLP, common lymphoid progenitor; LMP, lymphomyeloid progenitor; GMP, granulocyte-macrophage progenitor; MEP, megakaryocyte-erythroid progenitor; Lin, lineage-negative cells, the cell population not expressing surface lineage-specific marker molecules (Ter119, transferrin receptor, the marker of erythroid cells; В220, B-cell marker; Gr1, granulocyte marker; CD5, common marker for T- and B‑cells; CD8, T-cell marker; Mac1, marker of macrophages); cKit, the receptor of the stem cell growth factor; Sca1, stem cell antigen 1; Flk2, fetal liver kinase 2; CD34, an adhesion molecule, the marker of HSC; Slamf1, membrane protein lymphocyte receptor; IL7Ra, IL-7α receptor; CD27, a member of the tumor necrosis factor receptor superfamily; CD38, cyclic ADP ribose hydrolase; CD90, thymopoetin; CD49f, integrin α6; CD45RA, panleukocyte antigen isoform; Rho, rhodamin; CD10, B-cell marker; IL3Ra, IL-3 receptor; GFP, green fluorescent protein.

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Bigildeev, A.E., Petinati, N.A. & Drize, N.J. How Methods of Molecular Biology Shape Our Understanding of the Hematopoietic System. Mol Biol 53, 626–637 (2019). https://doi.org/10.1134/S0026893319050029

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