Twist1 regulates embryonic hematopoietic differentiation through binding to Myb and Gata2 promoter regions

Kasem Kulkeaw, Tomoko Inoue, Tadafumi Iino, Kenzaburo Tani, Koichi Akashi, Nancy A. Speck, Yoichi Nakanishi, Daisuke Sugiyama

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Mechanisms underlying differentiation of embryonic hematopoietic stem/progenitor cells (HSPCs) remain unclear. In mouse, intra-aortic clusters (IACs) form in the aorta-gonad-mesonephros region and acquire HSPC potential after 9.5 days postcoitum (dpc). In this study we demonstrate that Twist1 is highly expressed in c-Kit1CD311CD341 IACs, which are equivalent to embryonic HSPCs, compared with adult HSPCs. Progenitor activities of colony-forming unit (CFU) of granulocytes and macrophages, CFU of macrophages, burst-forming unit of erythroid, and B lymphopoiesis were impaired in IACs of Twist12/2 relative to wild-type embryos. Microarray analysis and real-time polymerase chain reaction showed downregulated expression of Myb and Gata2 transcripts in Twist12/2 IACs. Chromatin immunoprecipitation and promoter binding assays indicated that Twist1 directly binds the Myb and Gata2 promoters in 10.5-dpc IACs. We conclude that Twist1 is a novel transcriptional regulator of HSPC differentiation through direct binding to promoter regions of key regulators of the process.

Original languageEnglish
Pages (from-to)1672-1681
Number of pages10
JournalBlood Advances
Volume1
Issue number20
DOIs
Publication statusPublished - Sep 12 2017

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All Science Journal Classification (ASJC) codes

  • Hematology

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