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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REFERENCES
Maximow A. 1909. Der Lymphozyt als gemeinsame Stammzelle der verschiedenen Blutelemente in der embryonalen Entwicklung und im postfetalen Leben der Säugetiere. Folia Haematol., 125–134.
Maximow A.A. 1927. Development of non-granular leucocytes (lymphocytes and monocytes) into polyblasts (macrophages) and fibroblasts in vitro. Proc. Soc. Exp. Biol. Med. 24, 570–572.
Maximow A.A., Bloom W. 1952. A Textbook of Histology, 6th ed. Philadelphia: W.B. Saunders.
Lorenz E., Uphoff D., Reid T.R., Shelton E. 1951. Modification of irradiation injury in mice and guinea pigs by bone marrow injections. J. Natl. Cancer. Inst. 12, 197–201.
Jacobson L.O., Simmons E.L., Marks E.K., Eldredge J.H. 1951. Recovery from radiation injury. Science. 113, 510–511.
Till J.E., McCulloch E.A. 1961. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat. Res. 14, 213–222.
Becker A.J., McCulloch E.A., Till J.E. 1963. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature. 197, 452–454.
Abramson S., Miller R.G., Phillips R.A. 1977. The identification in adult bone marrow of pluripotent and restricted stem cells of the myeloid and lymphoid systems. J. Exp. Med. 145, 1567–1579.
Lemischka I.R., Raulet D.H., Mulligan R.C. 1986. Developmental potential and dynamic behavior of hematopoietic stem cells. Cell. 45, 917–927.
Morrison S.J., Uchida N., Weissman I.L. 1995. The biology of hematopoietic stem cells. Annu. Rev. Cell Dev. Biol. 11, 35–71.
Weissman I.L. 2000. Stem cells: Units of development, units of regeneration, and units in evolution. Cell. 100, 157–168.
Morrison S.J., Weissman I.L. 1994. The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity. 1, 661–673.
Deppe U., Schierenberg E., Cole T., Krieg C., Schmitt D., Yoder B., von Ehrenstein G. 1978. Cell lineages of the embryo of the nematode Caenorhabditis elegans. Proc. Natl. Acad. Sci. U. S. A. 75, 376–380.
Mintz B. 1967. Gene control of mammalian pigmentary differentiation: 1. Clonal origin of melanocytes. Proc. Natl. Acad. Sci. U. S. A. 58, 344–351.
Le Douarin N.M., Teillet M.A. 1973. The migration of neural crest cells to the wall of the digestive tract in avian embryo. J. Embryol. Exp. Morphol. 30, 31–48.
Lawson K.A., Meneses J.J., Pedersen R.A. 1986. Cell fate and cell lineage in the endoderm of the presomite mouse embryo, studied with an intracellular tracer. Dev. Biol. 115, 325–339.
Köhler G., Milstein C. 1975. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 256, 495–497.
Spangrude G.J., Heimfeld S., Weissman I.L. 1988. Purification and characterization of mouse hematopoietic stem cells. Science. 241, 58–62.
Muller-Sieburg C.E., Whitlock C.A., Weissman I.L. 1986. Isolation of two early B lymphocyte progenitors from mouse marrow: A committed pre-pre-B cell and a clonogenic Thy-1-lo hematopoietic stem cell. Cell. 44, 653–662.
Osawa M., Hanada K., Hamada H., Nakauchi H. 1996. Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science. 273, 242–245.
Akashi K., Traver D., Miyamoto T., Weissman I.L. 2000. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature. 404, 193–197.
Spangrude G.J. 1994. Biological and clinical aspects of hematopoietic stem cells. Annu. Rev. Med. 45, 93–104.
Kondo M., Weissman I.L., Akashi K. 1997. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell. 91, 661–672.
Wilson A., Laurenti E., Oser G., van der Wath R.C., Blanco-Bose W., Jaworski M., Offner S., Dunant C.F., Eshkind L., Bockamp E., Lió P., Macdonald H.R., Trumpp A. 2008. Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell. 135, 1118–1129.
Adolfsson J., Månsson R., Buza-Vidas N., Hultquist A., Liuba K., Jensen C.T., Bryder D., Yang L., Borge O.J., Thoren L.A., Anderson K., Sitnicka E., Sasaki Y., Sigvardsson M., Jacobsen S.E. 2005. Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment. Cell. 121, 295–306.
Vorob’ev A.A., Drize N.I., Chertkov I.L. 1995. The scheme of hematopoiesis. Probl. Gematol. 1, 7–14.
Doulatov S., Notta F., Laurenti E., Dick J.E. 2012. Hematopoiesis: A human perspective. Cell Stem Cell. 10, 120–136.
Cheung A.M., Leung D., Rostamirad S., Dhillon K., Miller P.H., Droumeva R., Brinkman R.R., Hogge D., Roy D.C., Eaves C.J. 2012. Distinct but phenotypically heterogeneous human cell populations produce rapid recovery of platelets and neutrophils post-transplant. Blood. 3431–3439.
Yamamoto R., Wilkinson A.C., Nakauchi H. 2018. Changing concepts in hematopoietic stem cells. Science. 362, 895–896.
Cho R.H., Sieburg H.B., Muller-Sieburg C.E. 2008. A new mechanism for the aging of hematopoietic stem cells: Aging changes the clonal composition of the stem cell compartment but not individual stem cells. Blood. 111, 5553–5561.
Muller-Sieburg C., Sieburg H.B., Bernitz J.M., Cattarossi G. 2012. Stem cell heterogeneity: Implications for aging and regenerative medicine. Blood. 119, 3900–3907.
Ema H., Morita Y., Suda T. 2014. Heterogeneity and hierarchy of hematopoietic stem cells. Exp. Hematol. 42, 74–82.e2.
Quesenberry P.J., Goldberg L.R., Dooner M.S. 2015. Concise reviews: A stem cell apostasy: A tale of four H words. Stem Cells. 33, 15–20.
Quesenberry P.J., Goldberg L., Aliotta J., Dooner M. 2014. Marrow hematopoietic stem cells revisited: They exist in a continuum and are not defined by standard purification approaches; then there are the microvesicles. Front Oncol. 4. 56.
Siminovitch L., Mcculloch E. A., Till J.E. 1963. The distribution of colony-forming cells among spleen colonies. J. Cell. Physiol. 62, 327–336.
Wu A.M., Till J.E., Siminovitch L., McCulloch E.A. 1968. Cytological evidence for a relationship between normal hematopoietic colony-forming cells and cells of the lymphoid system. J. Exp. Med. 127, 455–464.
Magli M.C., Dick J.E., Huszar D., Bernstein A., Phillips R.A. 1987. Modulation of gene expression in multiple hematopoietic cell lineages following retroviral vector gene transfer. Proc. Natl. Acad. Sci. U. S. A. 84, 789–793.
Dick J.E., Magli M.C., Huszar D., Phillips R.A., Bernstein A. 1985. Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/Wv mice. Cell. 42, 71–79.
Drize N.J., Keller J.R., Chertkov J.L. 1996. Local clonal analysis of the hematopoietic system shows that multiple small short-living clones maintain life-long hematopoiesis in reconstituted mice. Blood. 88, 2927–2938.
Drize N.I., Chertkov I.L. 2000. Clone-forming activity of embryonal stem hemopoietic cells after transplantation to newborn or adult sublethally irradiated mice. Bull. Exp. Biol Med. 130, 709–711.
Drize N., Chertkov J., Sadovnikova E., Tiessen S., Zander A. 1997. Long-term maintenance of hematopoiesis in irradiated mice by retrovirally transduced peripheral blood stem cells. Blood. 89, 1811–1817.
Olovnikova N.I., Drize N.J., Ershler M.A., Nifontova I.N., Belkina E. V, Nikolaeva T.N., Proskurina N.V., Chertkov J.L. 2003. Developmental fate of hematopoietic stem cells: The study of individual hematopoietic clones at the level of antigen-responsive B lymphocytes. Hematol. J. 4, 146–150.
Bystrykh L.V., Verovskaya E., Zwart E., Broekhuis M., de Haan G. 2012. Counting stem cells: Methodological constraints. Nat. Methods. 9, 567–574.
Deichmann A., Hacein-Bey-Abina S., Schmidt M., Garrigue A., Brugman M.H., Hu J., Glimm H., Gyapay G., Prum B., Fraser C.C., Fischer N., Schwarzwaelder K., Siegler M.L., de Ridder D., Pike-Overzet K., et al. 2007. Vector integration is nonrandom and clustered and influences the fate of lymphopoiesis in SCID-X1 gene therapy. J. Clin. Invest. 117, 2225–2232.
Bushman F.D., Torrey N., Rd P., Jolla L. 2003. Targeting survival: Intergation site selection by retroviruses and LTR-retrotransposons. Cell. 115 (2) 135–138.
Kustikova O., Fehse B., Modlich U., Yang M., Düllmann J., Kamino K., von Neuhoff N., Schlegelberger B., Li Z., Baum C. 2005. Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking. Science. 308, 1171–1174.
Stein S., Ott M.G., Schultze-Strasser S., Jauch A., Burwinkel B., Kinner A., Schmidt M., Krämer A., Schwäble J., Glimm H., Koehl U., Preiss C., Ball C., Martin H., Göhring G., et al. 2010. Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease. Nat. Med. 16, 198–204.
Glimm H., Ball C.R., von Kalle C. 2011. You can count on this: Barcoded hematopoietic stem cells. Cell Stem Cell. 9, 390–392.
Gerrits A., Dykstra B., Kalmykowa O.J., Klauke K., Verovskaya E., Broekhuis M.J.C., de Haan G., Bystrykh L.V. 2010. Cellular barcoding tool for clonal analysis in the hematopoietic system. Blood. 115, 2610–2618.
Rebrikov D.V., Korostin D.O., Shubina E.S., Il’inskii V.V. 2015. NGS: vysokoproizvoditel’noe sekvenirovanie (NGS: High-Throughput Sequencing). Moscow: Binom.
Biasco L., Pellin D., Scala S., Dionisio F., Basso-Ricci L., Leonardelli L., Scaramuzza S., Baricordi C., Ferrua F., Cicalese M.P., Giannelli S., Neduva V., Dow D.J., Schmidt M., Von Kalle C., et al. 2016. In vivo tracking of human hematopoiesis reveals patterns of clonal dynamics during early and steady-state reconstitution phases. Cell Stem Cell. 19, 107–119.
Lu R., Neff N.F., Quake S.R., Weissman I.L. 2011. Tracking single hematopoietic stem cells in vivo using high-throughput sequencing in conjunction with viral genetic barcoding. Nat. Biotechnol. 29, 928–933.
Maetzig T., Brugman M.H., Bartels S., Heinz N., Kustikova O.S., Modlich U., Li Z., Galla M., Schiedlmeier B., Schambach A., Baum C. 2011. Polyclonal fluctuation of lentiviral vector-transduced and expanded murine hematopoietic stem cells. Blood. 117, 3053–3064.
Verovskaya E., Broekhuis M.J.C., Zwart E., Ritsema M., van Os R., de Haan G., Bystrykh L.V. 2013. Heterogeneity of young and aged murine hematopoietic stem cells revealed by quantitative clonal analysis using cellular barcoding. Blood. 122, 523–532.
Xie Y., Yin T., Wiegraebe W., He X.C., Miller D., Stark D., Perko K., Alexander R., Schwartz J., Grindley J.C., Park J., Haug J.S., Wunderlich J.P., Li H., Zhang S., Johnson T., et al. 2009. Detection of functional haematopoietic stem cell niche using real-time imaging. Nature. 457, 97–101.
Guezguez B., Campbell C.J. V, Boyd A.L., Karanu F., Casado F.L., Di Cresce C., Collins T.J., Shapovalova Z., Xenocostas A., Bhatia M. 2013. Regional localization within the bone marrow influences the functional capacity of human HSCs. Cell Stem Cell. 13, 175–189.
Bystrykh L.V., de Haan G., Verovskaya E. 2014. Barcoded vector libraries and retroviral or lentiviral barcoding of hematopoietic stem cells. Methods Mol. Biol. 1185, 345–360.
Biasco L., Scala S., Basso Ricci L., Dionisio F., Baricordi C., Calabria A., Giannelli S., Cieri N., Barzaghi F., Pajno R., Al-Mousa H., Scarselli A., Cancrini C., Bordignon C., Roncarolo M.G., et al. 2015. In vivo tracking of T cells in humans unveils decade-long survival and activity of genetically modified T memory stem cells. Sci. Transl. Med. 7, 273ra13–273ra13.
Brugman M.H., Wiekmeijer A.-S., van Eggermond M., Wolvers-Tettero I., Langerak A.W., de Haas E.F.E., Bystrykh L.V., van Rood J.J., de Haan G., Fibbe W.E., Staal F.J. 2015. Development of a diverse human T-cell repertoire despite stringent restriction of hematopoietic clonality in the thymus. Proc. Natl. Acad. Sci. U. S. A. 112, E6020–E6027.
Kim S., Kim N., Presson A.P., Metzger M.E., Bonifacino A.C., Sehl M., Chow S.A., Crooks G.M., Dunbar C.E., An D.S., Donahue R.E., Chen I.S. 2014. Dynamics of HSPC repopulation in nonhuman primates revealed by a decade-long clonal-tracking study. Cell Stem Cell. 14, 473–485.
Genovese G., Kähler A.K., Handsaker R.E., Lindberg J., Rose S.A., Bakhoum S.F., Chambert K., Mick E., Neale B.M., Fromer M., Purcell S.M., Svantesson O., Landén M., Höglund M., Lehmann S., et al. 2014. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N. Engl. J. Med. 371, 2477–2487.
Jaiswal S., Fontanillas P., Flannick J., Manning A., Grauman P.V., Mar B.G., Lindsley R.C., Mermel C.H., Burtt N., Chavez A., Higgins J.M., Moltchanov V., Kuo F.C., Kluk M.J., Henderson B., et al. 2014. Age-related clonal hematopoiesis associated with adverse outcomes. N. Engl. J. Med. 371, 2488–2498.
Holstege H., Pfeiffer W., Sie D., Hulsman M., Nicholas T.J., Lee C.C., Ross T., Lin J., Miller M.A., Ylstra B., Meijers-Heijboer H., Brugman M.H., Staal F.J., Holstege G., Reinders M.J., et al. 2014. Somatic mutations found in the healthy blood compartment of a 115-year-old woman demonstrate oligoclonal hematopoiesis. Genome Res. 24, 733–742.
Sun J., Ramos A., Chapman B., Johnnidis J.B., Le L., Ho Y.-J., Klein A., Hofmann O., Camargo F.D. 2014. Clonal dynamics of native haematopoiesis. Nature. 514, 322–327.
Lu R. 2014. Sleeping beauty wakes up the clonal succession model for homeostatic hematopoiesis. Cell Stem Cell. 15, 677–678.
Busch K., Klapproth K., Barile M., Flossdorf M., Holland-Letz T., Schlenner S.M., Reth M., Höfer T., Rodewald H.R. 2015. Fundamental properties of unperturbed haematopoiesis from stem cells in vivo. Nature. 518, 542–546.
Rodriguez-Fraticelli A.E., Wolock S.L., Weinreb C.S., Panero R., Patel S.H., Jankovic M., Sun J., Calogero R.A., Klein A.M., Camargo F.D. 2018. Clonal analysis of lineage fate in native haematopoiesis. Nature. 553, 212–216.
Yamamoto R., Wilkinson A.C., Ooehara J., Lan X., Lai C.-Y., Nakauchi Y., Pritchard J.K., Nakauchi H. 2018. Large-scale clonal analysis resolves aging of the mouse hematopoietic stem cell compartment. Cell Stem Cell. 22, 600–607.e4.
Lu R., Czechowicz A., Seita J., Jiang D., Weissman I.L. 2019. Clonal-level lineage commitment pathways of hematopoietic stem cells in vivo. Proc. Natl. Acad. Sci. U. S. A. 116, 1447–1456.
Kester L., van Oudenaarden A. 2018. Single-cell transcriptomics meets lineage tracing. Cell Stem Cell. 23, 166–179.
Grün D., van Oudenaarden A. 2015. Design and analysis of single-cell sequencing experiments. Cell. 163, 799–810.
Haber A.L., Biton M., Rogel N., Herbst R.H., Shekhar K., Smillie C., Burgin G., Delorey T.M., Howitt M.R., Katz Y., Tirosh I., Beyaz S., Dionne D., Zhang M., Raychowdhury R., et al. 2017. A single-cell survey of the small intestinal epithelium. Nature. 551, 333–339.
Jaitin D.A., Kenigsberg E., Keren-Shaul H., Elefant N., Paul F., Zaretsky I., Mildner A., Cohen N., Jung S., Tanay A., Amit I. 2014. Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types. Science. 343, 776–779.
Klein A.M., Mazutis L., Akartuna I., Tallapragada N., Veres A., Li V., Peshkin L., Weitz D.A., Kirschner M.W. 2015. Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell. 161, 1187–1201.
Macosko E.Z., Basu A., Satija R., Nemesh J., Shekhar K., Goldman M., Tirosh I., Bialas A.R., Kamitaki N., Martersteck E.M., Trombetta J.J., Weitz D.A., Sanes J.R., Shalek A.K., Regev A., McCarroll S.A. 2015. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell. 161, 1202–1214.
Alemany A., Florescu M., Baron C.S., Peterson-Maduro J., van Oudenaarden A. 2018. Whole-organism clone tracing using single-cell sequencing. Nature. 556, 108–112.
Frieda K.L., Linton J.M., Hormoz S., Choi J., Chow K.-H.K., Singer Z.S., Budde M.W., Elowitz M.B., Cai L. 2017. Synthetic recording and in situ readout of lineage information in single cells. Nature. 541, 107–111.
Raj B., Wagner D.E., McKenna A., Pandey S., Klein A.M., Shendure J., Gagnon J.A., Schier A.F. 2018. Simultaneous single-cell profiling of lineages and cell types in the vertebrate brain. Nat. Biotechnol. 36, 442–450.
Spanjaard B., Hu B., Mitic N., Olivares-Chauvet P., Janjuha S., Ninov N., Junker J.P. 2018. Simultaneous lineage tracing and cell-type identification using CRISPR-Cas9-induced genetic scars. Nat. Biotechnol. 36, 469–473.
Yao Z., Mich J.K., Ku S., Menon V., Krostag A.-R., Martinez R.A., Furchtgott L., Mulholland H., Bort S., Fuqua M.A., Gregor B.W., Hodge R.D., Jayabalu A., May R.C., Melton S., et al. 2017. A single-cell roadmap of lineage bifurcation in human ESC models of embryonic brain development. Cell Stem Cell. 20, 120–134.
Tang F., Barbacioru C., Wang Y., Nordman E., Lee C., Xu N., Wang X., Bodeau J., Tuch B.B., Siddiqui A., Lao K., Surani M.A. 2009. mRNA-Seq whole-transcriptome analysis of a single cell. Nat. Methods. 6, 377–382.
Frank E., Sanes J.R. 1991. Lineage of neurons and glia in chick dorsal root ganglia: Analysis in vivo with a recombinant retrovirus. Development. 111, 895–908.
Turner D.L., Cepko C.L. 1987. A common progenitor for neurons and glia persists in rat retina late in development. Nature. 328, 131–136.
Pei W., Feyerabend T.B., Rössler J., Wang X., Postrach D., Busch K., Rode I., Klapproth K., Dietlein N., Quedenau C., Chen W., Sauer S., Wolf S., Höfer T., Rodewald H.R. 2017. Polylox barcoding reveals haematopoietic stem cell fates realized in vivo. Nature. 548, 456–460.
Jao L.-E., Wente S.R., Chen W. 2013. Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system. Proc. Natl. Acad. Sci. U. S. A. 110, 13904–13909.
Varshney G.K., Pei W., LaFave M.C., Idol J., Xu L., Gallardo V., Carrington B., Bishop K., Jones M., Li M., Harper U., Huang S.C., Prakash A., Chen W., Sood R., et al. 2015. High-throughput gene targeting and phenotyping in zebrafish using CRISPR/Cas9. Genome Res. 25, 1030–1042.
Paul F., Arkin Y., Giladi A., Jaitin D.A., Kenigsberg E., Keren-Shaul H., Winter D., Lara-Astiaso D., Gury M., Weiner A., David E., Cohen N., Lauridsen F.K., Haas S., Schlitzer A., et al. 2015. Transcriptional heterogeneity and lineage commitment in myeloid progenitors. Cell. 163, 1663–1677.
Laurenti E., Göttgens B. 2018. From haematopoietic stem cells to complex differentiation landscapes. Nature. 553, 418–426.
Carrelha J., Meng Y., Kettyle L.M., Luis T.C., Norfo R., Alcolea V., Boukarabila H., Grasso F., Gambardella A., Grover A., Högstrand K., Lord A.M., Sanjuan-Pla A., Woll P.S., Nerlov C., Jacobsen S.E.W. 2018. Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells. Nature. 554, 106–111.
Blaese R.M., Culver K.W., Miller A.D., Carter C.S., Fleisher T., Clerici M., Shearer G., Chang L., Chiang Y., Tolstoshev P., Greenblatt J.J., Rosenberg S.A., Klein H., Berger M., Mullen C.A., et al. 1995. T lymphocyte-directed gene therapy for ADA-SCID: Initial trial results after 4 years. Science. 270, 475–480.
Bordignon C., Notarangelo L.D., Nobili N., Ferrari G., Casorati G., Panina P., Mazzolari E., Maggioni D., Rossi C., Servida P., Ugazio A.G., Mavilio F. 1995. Gene therapy in peripheral blood lymphocytes and bone marrow for ADA- immunodeficient patients. Science. 270, 470–475.
Hilgendorf I., Greinix H., Halter J.P., Lawitschka A., Bertz H., Wolff D. 2015. Long-term follow-up after allogeneic stem cell transplantation. Dtsch. Aerzteblatt Online. 112, 51–58.
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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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DOI: https://doi.org/10.1134/S0026893319050029