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 K. Verma, Ying Liang, Juehua Gao, Peng Ji

Research output: Contribution to journalArticle

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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 (US)
Article number19589
JournalScientific Reports
Volume6
DOIs
StatePublished - Jan 21 2016

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Myelodysplastic Syndromes
Hematopoietic Stem Cells
Erythropoiesis
Hematopoiesis
Chromosome Deletion
Myeloid Cells
Knockout Mice
Anemia
Bone Marrow
Cell Line

ASJC Scopus subject areas

  • General

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H2AX deficiency is associated with erythroid dysplasia and compromised haematopoietic stem cell function. / Zhao, Baobing; Tan, Timothy L.; Mei, Yang; Yang, Jing; Yu, Yiting; Verma, Amit K.; Liang, Ying; Gao, Juehua; Ji, Peng.

In: Scientific Reports, Vol. 6, 19589, 21.01.2016.

Research output: Contribution to journalArticle

Zhao, Baobing ; Tan, Timothy L. ; Mei, Yang ; Yang, Jing ; Yu, Yiting ; Verma, Amit K. ; Liang, Ying ; Gao, Juehua ; Ji, Peng. / H2AX deficiency is associated with erythroid dysplasia and compromised haematopoietic stem cell function. In: Scientific Reports. 2016 ; Vol. 6.
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AU - Gao, Juehua

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