Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep29454
Title: Maintenance of the functional integrity of mouse hematopoiesis by EED and promotion of leukemogenesis by EED haploinsufficiency
Authors: Ikeda, K
Ueda, T
Yamasaki, N
Nakata, Y
Sera, Y
Nagamachi, A
Miyama, T
Kobayashi, H
Takubo, K
Kanai, A
Oda, H
Wolff, L
Honda, Z.-I
Ichinohe, T
Matsubara, A
Suda, T 
Inaba, T
Honda, H
Keywords: CD34 antigen
Eed protein, mouse
fibronectin
histone
polycomb repressive complex 2
small interfering RNA
animal
C57BL mouse
cell adhesion
cell cycle
cell differentiation
cell proliferation
cell transformation
chemistry
cytology
extracellular matrix
female
fetus blood
flow cytometry
gene transfer
genetics
haploinsufficiency
hematologic disease
hematopoiesis
hematopoietic stem cell
heterozygote
leukemia
male
metabolism
mouse
physiology
Animals
Antigens, CD34
Cell Adhesion
Cell Cycle
Cell Differentiation
Cell Proliferation
Cell Transformation, Neoplastic
Extracellular Matrix
Female
Fetal Blood
Fibronectins
Flow Cytometry
Gene Transfer Techniques
Haploinsufficiency
Hematologic Neoplasms
Hematopoiesis
Hematopoietic Stem Cells
Heterozygote
Histones
Leukemia
Male
Mice
Mice, Inbred C57BL
Polycomb Repressive Complex 2
RNA, Small Interfering
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Ikeda, K, Ueda, T, Yamasaki, N, Nakata, Y, Sera, Y, Nagamachi, A, Miyama, T, Kobayashi, H, Takubo, K, Kanai, A, Oda, H, Wolff, L, Honda, Z.-I, Ichinohe, T, Matsubara, A, Suda, T, Inaba, T, Honda, H (2016). Maintenance of the functional integrity of mouse hematopoiesis by EED and promotion of leukemogenesis by EED haploinsufficiency. Scientific Reports 6 : 29454. ScholarBank@NUS Repository. https://doi.org/10.1038/srep29454
Rights: Attribution 4.0 International
Abstract: Polycomb repressive complex 2 (PRC2) participates in transcriptional repression through methylation of histone H3K27. The WD-repeat protein embryonic ectoderm development (EED) is a non-catalytic but an essential component of PRC2 and its mutations were identified in hematopoietic malignancies. To clarify the role(s) of EED in adult hematopoiesis and leukemogenesis, we generated Eed conditional knockout (Eed "/ ") mice. Eed "/ " mice died in a short period with rapid decrease of hematopoietic cells. Hematopoietic stem/progenitor cells (HSPCs) were markedly decreased with impaired bone marrow (BM) repopulation ability. Cell cycle analysis of HSPCs demonstrated increased S-phase fraction coupled with suppressed G0/G1 entry. Genes encoding cell adhesion molecules are significantly enriched in Eed "/ " HSPCs, and consistently, Eed "/ " HSPCs exhibited increased attachment to a major extracellular matrix component, fibronectin. Thus, EED deficiency increases proliferation on one side but promotes quiescence possibly by enhanced adhesion to the hematopoietic niche on the other, and these conflicting events would lead to abnormal differentiation and functional defect of Eed "/ " HSPCs. In addition, Eed haploinsufficiency induced hematopoietic dysplasia, and Eed heterozygous mice were susceptible to malignant transformation and developed leukemia in cooperation with Evi1 overexpression. Our results demonstrated differentiation stage-specific and dose-dependent roles of EED in normal hematopoiesis and leukemogenesis.
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/182444
ISSN: 2045-2322
DOI: 10.1038/srep29454
Rights: Attribution 4.0 International
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