NUP98-HOXA10hd fusion protein sustains multi-lineage haematopoiesis of lineage-committed progenitors in transplant setting.
Cell Prolif
; 53(9): e12885, 2020 Sep.
Article
em En
| MEDLINE
| ID: mdl-32725842
ABSTRACT
OBJECTIVES:
Exploring approaches of extending the haematopoiesis time window of MPPs and lineage-committed progenitors might produce promising therapeutic effects. NUP98-HOXA10hd (NA) fusion protein can expand long-term haematopoietic stem cells (HSCs) and promote engraftment competitiveness without causing obvious oncogenesis. Our objectives were to investigate the roles of NA fusion protein in MPP and downstream lineage-committed progenitor context. MATERIAL ANDMETHODS:
300 sorted MPPs (Lin- CD48- c-kit+ Sca1+ CD135+ CD150- ) were mixed with 5 × 105 total BM helper/competitor cells and injected into irradiated recipients. For secondary transplantation, 5 × 106 total BM cells from primary recipient mice were injected into lethally irradiated recipients. NA-MPP recipient mice were sacrified for flow cytometric analysis of bone marrow progenitors at indicated time points. Sorted MPPs and myeloid progenitors were used for RNA-seq library preparation.RESULTS:
We showed that NA-expressing MPPs achieved significantly longer multi-lineage haematopoiesis (>44-week) than natural MPPs (20-week). NA upregulated essential genes regulating long-term haematopoiesis, cell cycle, epigenetic regulation and responses to stress in MPPs. These molecular traits are associated with the earlier appearance of a Sca1- c-kit+ myeloid progenitor population, and more abundant cellularity of lineage-committed progenitor as well as bone marrow nucleated cells. Further, the NA-derived primary bone marrow cells, which lack NA-LSK cells, successfully repopulated secondary multi-lineage haematopoiesis over 20 weeks.CONCLUSIONS:
This study unveiled that NA fusion protein promotes MPP and lineage-committed progenitor engraftment via extending long-term multi-lineage haematopoiesis.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transplante de Células-Tronco Hematopoéticas
/
Complexo de Proteínas Formadoras de Poros Nucleares
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Proteínas Homeobox A10
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Hematopoese
Limite:
Animals
Idioma:
En
Revista:
Cell Prolif
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China