H2AX deficiency is associated with erythroid dysplasia and compromised haematopoietic stem cell function

Baobing Zhao, Timothy L. Tan, Yang Mei, Jing Yang, Yiting Yu, Amit Verma, Ying Liang, Juehua Gao, Peng Ji

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Myelodysplastic syndromes (MDS) are clonal disorders of haematopoiesis characterised by dysplastic changes of major myeloid cell lines. However, the mechanisms underlying these dysplastic changes are poorly understood. Here, we used a genetically modified mouse model and human patient data to examine the physiological roles of H2AX in haematopoiesis and how the loss of H2AX contributes to dyserythropoiesis in MDS. H2AX knockout mice showed cell-autonomous anaemia and erythroid dysplasia, mimicking dyserythropoiesis in MDS. Also, dyserythropoiesis was increased in MDS patients with the deletion of chromosome 11q23, where H2AX is located. Although loss of H2AX did not affect the early stage of terminal erythropoiesis, enucleation was decreased. H2AX deficiency also led to the loss of quiescence of hematopoietic stem and progenitor cells, which dramatically compromised their bone marrow engraftment. These results reveal important roles of H2AX in late-stage terminal erythropoiesis and hematopoietic stem cell function.

Original languageEnglish
Article number19589
JournalScientific Reports
Volume6
DOIs
StatePublished - Jan 21 2016

Bibliographical note

Funding Information:
We thank Dr. Lin Li of the Mouse Histology and Phenotyping Laboratory of Northwestern University for help with mouse histology, and Bella Shmaltsuyeva of the Pathology Core Facility of Northwestern University for help with H2AX immunohistochemistry. This work is supported by the National Institutes of Health Pathway to Independence award (R00HL102154), the National Institute of Diabetes and Digestive and Kidney Diseases grant (R01DK102718), and the American Society for Hematology scholar award to P.J.

ASJC Scopus subject areas

  • General

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