Affordable Access

deepdyve-link
Publisher Website

Disruption of erythroid nuclear opening and histone release in myelodysplastic syndromes.

Authors
  • Zhao, Baobing1, 2
  • Liu, Hui3
  • Mei, Yang1
  • Liu, Yijie1
  • Han, Xu1
  • Yang, Jing1
  • Wickrema, Amittha3
  • Ji, Peng1
  • 1 Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
  • 2 Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Shandong University, Jinan, China. , (China)
  • 3 Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois.
Type
Published Article
Journal
Cancer Medicine
Publisher
Wiley
Publication Date
Mar 01, 2019
Volume
8
Issue
3
Pages
1169–1174
Identifiers
DOI: 10.1002/cam4.1969
PMID: 30701702
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Mammalian terminal erythropoiesis involves several characteristic phenomena including chromatin condensation and enucleation. One of the newly identified features of terminal erythropoiesis in mouse is a dynamic nuclear opening and histone release process, which is required for chromatin condensation. However, it is unclear whether the same feature is present in human. Here, we use an in vitro human CD34-positive hematopoietic stem and progenitor cell culture system and reveal that nuclear openings and histone release are also identified during human terminal erythropoiesis. In contrast to mouse in which each erythroblast contains a single opening, multiple nuclear openings are present in human erythroblast, particularly during the late-stage differentiation. The nuclear opening and histone release process is mediated by caspase-3. Inhibition of caspase-3 blocks nuclear opening, histone release, chromatin condensation, and terminal differentiation. We confirm the finding of histone cytosolic release in paraffin-embedded human bone marrow in vivo. Importantly, we find that patients with myelodysplastic syndrome (MDS) exhibit significant defects in histone release in the dysplastic erythroblasts. Our results reveal developmentally conserved nuclear envelop and histone dynamic changes in human terminal erythropoiesis and indicate that disruption of the histone release process plays a critical role in the pathogenesis of dyserythropoiesis in MDS. © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Report this publication

Statistics

Seen <100 times