Abstract
The most common cell type in the human body, the red blood cell or erythrocyte, has a life span of approximately 3 months. To compensate for this massive cellular requirement and short life span, the major blood producing tissues contain vast numbers of erythroid progenitor cells. Erythroid progenitors differentiate progressively from hematopoietic stem cells to committed erythroid progenitors to reticulocytes lacking a nucleus and finally to functionally mature erythrocytes in the circulation. Different erythroid progenitor activity, representative of distinct stages of erythropoiesis, can be observed using semisolid colony assays. Distinct stages of erythroid maturation can also be monitored by flow cytometry. Here, we discuss the range of different technical approaches that are used to identify and quantify erythroid progenitors, with particular focus on the mouse as a model system.
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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 Haematologica. pp 125–134
Lappin TR, Rich IN (1996) Erythropoietin—the first 90 years. Clin Lab Haematol 18:137–145
Mizel SB, Farrar JJ (1979) Revised nomenclature for antigen-nonspecific T cell proliferation and helper factors. Cell Immunol 48(2):433–436
Orkin SH, Zon LI (2008) SnapShot: hematopoiesis. Cell 132:712.e1–712.e2
Al-Drees MA, Yeo JH, Boumelhem BB et al (2015) Making blood: the haematopoietic niche throughout ontogeny. Stem Cells Int 2015:571893
Palis J (2014) Primitive and definitive erythropoiesis in mammals. Front Physiol 5:3
Sanchez M, Weissman IL, Pallavicini M et al (2006) Differential amplification of murine bipotent megakaryocytic/erythroid progenitor and precursor cells during recovery from acute and chronic erythroid stress. Stem Cells 24:337–348
Chen K, Liu J, Heck S et al (2009) Resolving the distinct stages in erythroid differentiation based on dynamic changes in membrane protein expression during erythropoiesis. Proc Natl Acad Sci 106:17413–17418
Kina T, Ikuta K, Takayama E et al (2000) The monoclonal antibody TER-119 recognizes a molecule associated with glycophorin A and specifically marks the late stages of murine erythroid lineage. Br J Haematol 109:280–287
Socolovsky M, Nam H-S, Fleming MD et al (2001) Ineffective erythropoiesis in Stat5a−/−5b−/− mice due to decreased survival of early erythroblasts. Blood 98(12):3261–3273
Koulnis M, Pop R, Porpiglia E et al (2011) Identification and analysis of mouse erythroid progenitors using the CD71/TER119 flow-cytometric assay. J Vis Exp e2809–e2809
Fraser ST, Isern J, Baron MH (2007) Maturation and enucleation of primitive erythroblasts during mouse embryogenesis is accompanied by changes in cell-surface antigen expression. Blood 109:343–352
Yeo JH, McAllan BM, Fraser ST (2016) Scanning electron microscopy reveals two distinct classes of erythroblastic island isolated from adult mammalian bone marrow. Microsc Microanal 22:368–378
Palis J, Robertson S, Kennedy M et al (1999) Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development 126:5073–5084
Fraser ST, Midwinter RG, Berger BS et al (2011) Heme oxygenase-1: a critical link between iron metabolism, erythropoiesis, and development. Adv Hematol 2011:1–6
Baron MH, Isern J, Fraser ST (2012) The embryonic origins of erythropoiesis in mammals. Blood 119:4828–4837
Wong PM, Chung SW, Reicheld SM et al (1986) Hemoglobin switching during murine embryonic development: evidence for two populations of embryonic erythropoietic progenitor cells. Blood 67:716–721
Isern J, He Z, Fraser ST et al (2011) Single-lineage transcriptome analysis reveals key regulatory pathways in primitive erythroid progenitors in the mouse embryo. Blood 117:4924–4934
Iscove NN, Sieber F (1975) Erythroid progenitors in mouse bone marrow detected by macroscopic colony formation in culture. Exp Hematol 3:32–43
Lodish H, Flygare J, Chou S (2010) From stem cell to erythroblast: regulation of red cell production at multiple levels by multiple hormones. IUBMB Life 62:492–496
Stephenson JR, Axelrad AA, McLeod DL et al (1971) Induction of colonies of hemoglobin-synthesizing cells by erythropoietin in vitro. Proc Natl Acad Sci U S A 68:1542–1546
Wu H, Liu X, Jaenisch R et al (1995) Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor. Cell 83:59–67
Hattangadi SM, Wong P, Zhang L et al (2011) From stem cell to red cell: regulation of erythropoiesis at multiple levels by multiple proteins, RNAs and chromatin modifications. Blood 118(24):6258–6268
Terszowski G (2005) Prospective isolation and global gene expression analysis of the erythrocyte colony-forming unit (CFU-E). Blood 105:1937–1945
Stumpf M, Waskow C, Krötschel M et al (2006) The mediator complex functions as a coactivator for GATA-1 in erythropoiesis via subunit Med1/TRAP220. Proc Natl Acad Sci U S A 103:18504–18509
Flygare J, Estrada VR, Shin C et al (2011) HIF1 synergizes with glucocorticoids to promote BFU-E progenitor self-renewal. Blood 117:3435–3444
Tusi BK, Wolock SL, Weinreb C et al (2018) Population snapshots predict early haematopoietic and erythroid hierarchies. Nature 555:54–60
Li J, Hale J, Bhagia P et al (2014) Isolation and transcriptome analyses of human erythroid progenitors: BFU-E and CFU-E. Blood 124:3636–3645
Lenox LE, Perry JM, Paulson RF (2005) BMP4 and Madh5 regulate the erythroid response to acute anemia. Blood 105:2741–2748
Perry JM, Harandi OF, Paulson RF (2007) BMP4, SCF, and hypoxia cooperatively regulate the expansion of murine stress erythroid progenitors. Blood 109:4494–4502
Perry JM, Harandi OF, Porayette P et al (2009) Maintenance of the BMP4-dependent stress erythropoiesis pathway in the murine spleen requires hedgehog signaling. Blood 113:911–918
Socolovsky M (2007) Molecular insights into stress erythropoiesis. Curr Opin Hematol 14:215–224
Porayette P, Paulson RF (2008) BMP4/Smad5 dependent stress erythropoiesis is required for the expansion of erythroid progenitors during fetal development. Dev Biol 317:24–35
Harandi OF, Hedge S, Wu D-C et al (2010) Murine erythroid short-term radioprotection requires a BMP4-dependent, self-renewing population of stress erythroid progenitors. J Clin Invest 120:4507–4519
Xiang J, Wu DC, Chen Y et al (2015) In vitro culture of stress erythroid progenitors identifies distinct progenitor populations and analogous human progenitors. Blood 125:1803–1812
Antoniou M (1991) Induction of erythroid-specific expression in murine erythroleukemia (MEL) cell lines. Methods Mol Biol 7:421–434
Socolovsky M (2001) Ineffective erythropoiesis in Stat5a−/−5b−/− mice due to decreased survival of early erythroblasts. Blood 98:3261–3273
Fraser ST, Isern J, Baron MH (2010) Use of transgenic fluorescent reporter mouse lines to monitor hematopoietic and erythroid development during embryogenesis. Methods Enzymol 476:403–427
Nakano T, Kodama H, Honjo T (1994) Generation of lymphohematopoietic cells from embryonic stem cells in culture. Science 265:1098–1101
Fraser ST, Ogawa M, Yu RT et al (2002) Definitive hematopoietic commitment within the embryonic vascular endothelial-cadherin(+) population. Exp Hematol 30:1070–1078
Schroeder T, Fraser ST, Ogawa M et al (2003) Recombination signal sequence-binding protein Jkappa alters mesodermal cell fate decisions by suppressing cardiomyogenesis. Proc Natl Acad Sci U S A 100:4018–4023
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Colonne, C.K., Yeo, J.H., McKenzie, C.V., Fraser, S.T. (2019). Identification and Analysis of Mouse Erythroid Progenitor Cells. In: Joglekar, M., Hardikar, A. (eds) Progenitor Cells. Methods in Molecular Biology, vol 2029. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9631-5_11
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DOI: https://doi.org/10.1007/978-1-4939-9631-5_11
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