Comprehensive phenotyping of erythropoiesis in human bone marrow: Evaluation of normal and ineffective erythropoiesis
Hongxia Yan
(1)
,
Abdullah Ali
(2)
,
Lionel Blanc
(3, 4)
,
Anupama Narla
(5)
,
Joseph Lane
(6)
,
Erjing Gao
(1)
,
Julien Papoin
(4)
,
John Hale
,
Christopher Hillyer
(1)
,
Naomi Taylor
(7)
,
Patrick Gallagher
(8)
,
Azra Raza
(9)
,
Sandrina Kinet
(7)
,
Narla Mohandas
(1)
1
New York Blood Center
2 Columbia University [New York]
3 Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
4 The Feinstein Institute for Medical Research
5 Stanford University
6 Hospital for Special Surgery
7 Hematopoïèse et Immunothérapie
8 YSM - Yale School of Medicine [New Haven, Connecticut]
9 CUIMC - Columbia University Irving Medical Center
2 Columbia University [New York]
3 Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
4 The Feinstein Institute for Medical Research
5 Stanford University
6 Hospital for Special Surgery
7 Hematopoïèse et Immunothérapie
8 YSM - Yale School of Medicine [New Haven, Connecticut]
9 CUIMC - Columbia University Irving Medical Center
Julien Papoin
- Fonction : Auteur
- PersonId : 1226620
- ORCID : 0000-0002-5446-6469
John Hale
- Fonction : Auteur
Naomi Taylor
- Fonction : Auteur
- PersonId : 857337
- ORCID : 0000-0002-2459-4558
- IdRef : 069480672
Sandrina Kinet
- Fonction : Auteur
- PersonId : 740239
- IdHAL : sandrina-kinet
- ORCID : 0000-0003-0699-108X
- IdRef : 195695437
Narla Mohandas
- Fonction : Auteur
- PersonId : 762283
- ORCID : 0000-0003-2271-5296
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.
Domaines
HématologieFormat du dépôt | Fichier |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Comprehensive phenotyping of erythropoiesis in human bone marrow: Evaluation of normal and ineffective erythropoiesis
|
Résumé |
en
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.
|
Auteur(s) |
Hongxia Yan
1
, Abdullah Ali
2
, Lionel Blanc
3, 4
, Anupama Narla
5
, Joseph Lane
6
, Erjing Gao
1
, Julien Papoin
4
, John Hale
, Christopher Hillyer
1
, Naomi Taylor
7
, Patrick Gallagher
8
, Azra Raza
9
, Sandrina Kinet
7
, Narla Mohandas
1
1
New York Blood Center
( 345810 )
- 310 E 67th St
New York, NY 10065
- États-Unis
2
Columbia University [New York]
( 75524 )
- Columbia University in the City of New York, 2960 Broadway, New York, NY 10027-6902
- États-Unis
3
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
( 1007733 )
- New Hyde Park, New York
- États-Unis
4
The Feinstein Institute for Medical Research
( 533372 )
- 350 Community Dr, Manhasset, NY 11030, États-Unis
- États-Unis
5
Stanford University
( 73500 )
- 450 Serra Mall, Stanford, CA 94305-2004
- États-Unis
6
Hospital for Special Surgery
( 358726 )
- 535 E 70th St, New York, NY 10021, États-Unis
- États-Unis
7
Hematopoïèse et Immunothérapie
( 1077717 )
- France
8
YSM -
Yale School of Medicine [New Haven, Connecticut]
( 51214 )
- Yale University School of Medicine - 333 Cedar Street - New Haven, CT 06510
- États-Unis
9
CUIMC -
Columbia University Irving Medical Center
( 320799 )
- Columbia University Medical Center
622 W 168th St, New York, NY 10032, États-Unis
- États-Unis
|
Langue du document |
Anglais
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Volume |
96
|
Numéro |
9
|
Page/Identifiant |
1064-1076
|
Date de publication |
2021
|
Mots-clés (Mesh) |
|
Domaine(s) |
|
DOI | 10.1002/ajh.26247 |
Pubmed Id | 34021930 |
PubMed Central | PMC8355124 |
Origine :
Fichiers produits par l'(les) auteur(s)
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