Comprehensive phenotyping of erythropoiesis in human bone marrow: Evaluation of normal and ineffective erythropoiesis.
Journal
American journal of hematology
ISSN: 1096-8652
Titre abrégé: Am J Hematol
Pays: United States
ID NLM: 7610369
Informations de publication
Date de publication:
01 09 2021
01 09 2021
Historique:
received:
17
05
2021
accepted:
18
05
2021
pubmed:
23
5
2021
medline:
30
9
2021
entrez:
22
5
2021
Statut:
ppublish
Résumé
Identification of stage-specific erythroid cells is critical for studies of normal and disordered human erythropoiesis. While immunophenotypic strategies have previously been developed to identify cells at each stage of terminal erythroid differentiation, erythroid progenitors are currently defined very broadly. Refined strategies to identify and characterize BFU-E and CFU-E subsets are critically needed. To address this unmet need, a flow cytometry-based technique was developed that combines the established surface markers CD34 and CD36 with CD117, CD71, and CD105. This combination allowed for the separation of erythroid progenitor cells into four discrete populations along a continuum of progressive maturation, with increasing cell size and decreasing nuclear/cytoplasmic ratio, proliferative capacity and stem cell factor responsiveness. This strategy was validated in uncultured, primary erythroid cells isolated from bone marrow of healthy individuals. Functional colony assays of these progenitor populations revealed enrichment of BFU-E only in the earliest population, transitioning to cells yielding BFU-E and CFU-E, then CFU-E only. Utilizing CD34/CD105 and GPA/CD105 profiles, all four progenitor stages and all five stages of terminal erythroid differentiation could be identified. Applying this immunophenotyping strategy to primary bone marrow cells from patients with myelodysplastic syndrome, identified defects in erythroid progenitors and in terminal erythroid differentiation. This novel immunophenotyping technique will be a valuable tool for studies of normal and perturbed human erythropoiesis. It will allow for the discovery of stage-specific molecular and functional insights into normal erythropoiesis as well as for identification and characterization of stage-specific defects in inherited and acquired disorders of erythropoiesis.
Identifiants
pubmed: 34021930
doi: 10.1002/ajh.26247
pmc: PMC8355124
mid: NIHMS1707817
doi:
Substances chimiques
Antigens, CD
0
Antigens, CD34
0
Endoglin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1064-1076Subventions
Organisme : NIDDK NIH HHS
ID : P01 DK032094
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL144436
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL152099
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Informations de copyright
© 2021 Wiley Periodicals LLC.
Références
Blood. 1982 Sep;60(3):703-13
pubmed: 6286014
Curr Opin Hematol. 2017 May;24(3):159-166
pubmed: 28099275
Stem Cells. 2018 Aug;36(8):1138-1145
pubmed: 29658164
Cytometry B Clin Cytom. 2004 Jul;60(1):1-13
pubmed: 15221864
Blood. 2015 Apr 16;125(16):2553-7
pubmed: 25755292
Blood. 1989 Jan;73(1):100-3
pubmed: 2910352
J Clin Med. 2019 Dec 02;8(12):
pubmed: 31810354
Nat Biotechnol. 2005 Jan;23(1):69-74
pubmed: 15619619
Am J Hematol. 2018 Aug;93(4):494-503
pubmed: 29274096
Leukemia. 1990 Sep;4(9):657-63
pubmed: 2395385
Blood. 1987 Nov;70(5):1316-24
pubmed: 3117132
Proc Natl Acad Sci U S A. 1971 Jul;68(7):1542-6
pubmed: 4104431
Blood. 2014 Dec 4;124(24):3636-45
pubmed: 25339359
Int J Lab Hematol. 2014 Apr;36(2):184-96
pubmed: 24118926
J Clin Invest. 2020 Apr 1;130(4):2097-2110
pubmed: 31961825
Cell Rep. 2018 Nov 20;25(8):2083-2093.e4
pubmed: 30463007
Blood. 1987 Jan;69(1):255-63
pubmed: 2947644
Blood Adv. 2018 Jun 26;2(12):1393-1402
pubmed: 29903708
Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11872-7
pubmed: 12193648
N Engl J Med. 2021 Feb 25;384(8):727-743
pubmed: 33626255
Blood. 1983 Jun;61(6):1242-6
pubmed: 6188507
Blood. 1998 Nov 15;92(10):3658-68
pubmed: 9808559
Stem Cells Transl Med. 2012 Dec;1(12):927-33
pubmed: 23283554
Nature. 1981 Jan 1;289(5793):68-71
pubmed: 6161308
Leukemia. 1991 Oct;5(10):841-7
pubmed: 1961019
Cell Stem Cell. 2007 Oct 11;1(4):428-42
pubmed: 18371379
Blood. 2005 Mar 1;105(5):1937-45
pubmed: 15522951
Blood. 2016 Aug 18;128(7):923-33
pubmed: 27268089
Blood. 1992 Aug 1;80(3):642-50
pubmed: 1638021
Blood. 1991 Nov 15;78(10):2493-7
pubmed: 1726703
Anal Cell Pathol. 1990 Jul;2(4):229-40
pubmed: 1703434
Blood. 2013 Apr 18;121(16):3246-53
pubmed: 23422750
Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):9638-43
pubmed: 26195758
J Immunol. 1995 May 1;154(9):4456-65
pubmed: 7722302
Front Physiol. 2014 Jan 28;5:3
pubmed: 24478716
Int J Mol Sci. 2020 Jul 24;21(15):
pubmed: 32722249