Hemp, an mbt domain-containing protein, plays essential roles in hematopoietic stem cell function and skeletal formation

Hiroaki Honda, Keiyo Takubo, Hideaki Oda, Kenjiro Kosaki, Tatsuya Tazaki, Norimasa Yamasaki, Kazuko Miyazaki, Kateri A. Moore, Zen Ichiro Honda, Toshio Suda, Ihor R. Lemischka

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

To clarify the molecular pathways governing hematopoietic stem cell (HSC) development, we screened a fetal liver (FL) HSC cDNA library and identified a unique gene, hematopoietic expressed mammalian polycomb (hemp), encoding a protein with a zinc-finger domain and four malignant brain tumor (mbt) repeats. To investigate its biological role, we generated mice lacking Hemp (hemp -/-). Hemp-/- mice exhibited a variety of skeletal malformations and died soon after birth. In the FL, hemp was preferentially expressed in the HSC and early progenitor cell fractions, and analyses of fetal hematopoiesis revealed that the number of FL mononuclear cells, including HSCs, was reduced markedly in hemp-/- embryos, especially during early development. In addition, colony-forming and competitive repopulation assays demonstrated that the proliferative and reconstitution abilities of hemp -/- FL HSCs were significantly impaired. Microarray analysis revealed alterations in the expression levels of several genes implicated in hematopoietic development and differentiation in hemp-/- FL HSCs. These results demonstrate that Hemp, an mbt-containing protein, plays essential roles in HSC function and skeletal formation. It is also hypothesized that Hemp might be involved in certain congenital diseases, such as Klippel-Feil anomaly.

Original languageEnglish
Pages (from-to)2468-2473
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number6
DOIs
Publication statusPublished - 2011 Feb 8

Keywords

  • Fetal liver hematopoiesis
  • Skeletal abnormality

ASJC Scopus subject areas

  • General

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