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Cellular Components of Blood
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Red blood cells are formed in the bone marrow, and the most primitive cell is the proerythroblast. Over a period of 5 days, the proerythroblast gives rise to a series of progressively smaller normoblasts by undergoing cell division and maturation. The erythroblasts progressively contain more haemoglobin (Hb), while the nuclear chromatin becomes more condensed. Eventually, a pyknotic nucleus is extruded from the late erythroblast to form a reticulocyte, which is the first red cell to enter the circulation (Figure 51.2).
Diamond-Blackfan Anemia
Published in Stephen A. Feig, Melvin H. Freedman, Clinical Disorders and Experimental Models of Erythropoietic Failure, 2019
Jeffrey M. Lipton, Blanche P. Alter
In the more than 50 years from the first descriptions, there have been many theories regarding etiology. The myriad explanations include humoral7 or cellular8,9 suppression of erythropoiesis, a microenvironmental defect,10 a block in the erythroid maturation pathway,11 failure of accessory cells,12 and a defect intrinsic to erythroid progenitor cells.13–15 Recent data suggest that the pathway from the multipotent myeloid progenitor to the mature erythroid progenitor is essentially intact but that terminal differentiation to the proerythroblast and beyond is defective.14,15 With this last model in mind, the following discussion will concentrate on the development of diagnostic criteria and treatment based upon pathophysiology.
Hormonal Regulation of Cell Proliferation and Differentiation
Published in Jean Morisset, Travis E. Solomon, Growth of the Gastrointestinal Tract: Gastrointestinal Hormones and Growth Factors, 2017
Our whole embryological development would not be possible without the process of differentiation. However, one of the consequences of differentiation is the loss of cellular plasticity.44 This means that the acquisition of certain differentiated functions by a particular progenitor cell most often precludes it from acquiring other differentiated functions. For example, in the case of the red blood cell, a pluripotential stem cell divides to produce either additional stem cells or proerythroblasts. The proerythroblast, through a series of intermediate stages, is committed to become a mature red blood cell and cannot assume other pathways of differentiation.45 In contrast to the red blood cell, many other differentiated cells retain the capacity to undergo mitosis and to produce identically differentiated daughter cells. Further, in some instances the daughter cells regain a certain degree of plasticity and exhibit new differentiated functions — a phenomenon that has been called metaplasia or transdifferentia-tion.46
Beyond neurodegenerative diseases: α-synuclein in erythropoiesis
Published in Hematology, 2022
Ling Ling, Fangfang Wang, Duonan Yu
Nearly all erythroid precursors in human bone marrows strongly express α-syn [37]. Further studies demonstrated that α-syn is differentially expressed during erythropoiesis. In culture of human CD34+ cells from peripheral blood, the α-syn gene starts transcription in the erythroid colony forming unit (CFU-E) stage and reaches peak levels in the late stage of erythroblasts (around orthochromatic stage), whereas protein levels from monomers reach the highest in terminal differentiation stages (enucleated cells) (Figure 2) [14]. Interestingly, a high molecular protein band (over 100 kDa) can be detected in the early stage of erythroblasts (CFU-E and proerythroblast) but have not been confirmed as an oligomeric form of α-syn [14]. Notably, the concentration of total α-syn (but not oligomeric α-syn) in peripheral erythrocytes in older people is relatively lower than that in younger individuals, possibly due to the DNA methylation of intron-1 of the SNCA gene [38].
The state of the art of fetal hemoglobin-inducing agents
Published in Expert Opinion on Drug Discovery, 2022
Aline Renata Pavan, Juliana Romano Lopes, Jean Leandro Dos Santos
Screening small and large libraries of compounds led to the discovery of new HbF-inducing agents. The models used to establish a High Throughput Screening (HTS) platform, a cell-based reporter assay using immortalized cells (i.e. K562), in which the locus control region (LCR) is linked to the γ-globin promoter added to the green fluorescent protein (EGFP) or the red fluorescent protein (RFP) reporter gene, have been described [13,14]. Immortalized cell lines have characteristics that are suitable for large-scale trials. Among those, K562 cells and HUDEP-2 have been used in HTS experiments. K562 cells are immortalized lymphoblasts isolated from a 53-year-old female diagnosed with chronic myelogenous leukemia. HUDEP-2 is an immortalized proerythroblast cell line that is used to evaluate 15].
Melanoma induced immunosuppression is mediated by hematopoietic dysregulation
Published in OncoImmunology, 2018
Neha Kamran, Youping Li, Maria Sierra, Mahmoud S. Alghamri, Padma Kadiyala, Henry D. Appelman, Marta Edwards, Pedro R. Lowenstein, Maria G. Castro
Melanoma bearing mice were observed to be severely anemic. Therefore, we next analyzed the erythroid precursors in these mice. Interestingly, a 4.8 fold increase (18.94 ± 1.41 vs. 3.98 ± 0.83) in the percentage of reticulocytes and a 5.2 fold increase (1793 ± 335.2 vs. 344.5 ± 15.99) in the absolute number of reticulocytes was observed in the peripheral blood of melanoma mice indicating an increase in erythroid precursor cells which was in contrast with the decreased number of mature RBCs (Fig. 2Ai-ii). To further investigate the apparent discrepancy between the number of mature RBCs and reticulocytes we made use of CD71 and Ter119 expression that have been used to delineate the proerythroblast, early erythroblast, late erythroblast and reticulocyte stages of RBC generation (Fig. 2B).25 In mice the BM and the spleen are sites of erythropoiesis especially under stress 25,26; detailed analysis of melanoma spleens and BM showed an increase in the percentage of CD71+, Ter119- cells (proerythroblasts), increase in CD71+, Ter119+ cells (early erythroblasts) and a decrease in the CD71-, Ter119+ cells (late erythroblasts/reticulocytes) compared to NT mice in the spleen and BM (Fig. 2C-D). Overall, we observed that while the pro and early erythroblasts were increased in the spleen and BM indicating increased erythropoiesis, melanoma bearing mice were anemic likely due to the decreased proportion of late erythroblasts and elevated reticulocytes (Fig. 2).