論文

査読有り 国際誌
2019年4月25日

Epigenetic control of early dendritic cell lineage specification by the transcription factor IRF8 in mice.

Blood
  • Daisuke Kurotaki
  • ,
  • Wataru Kawase
  • ,
  • Haruka Sasaki
  • ,
  • Jun Nakabayashi
  • ,
  • Akira Nishiyama
  • ,
  • Herbert C Morse 3rd
  • ,
  • Keiko Ozato
  • ,
  • Yutaka Suzuki
  • ,
  • Tomohiko Tamura

133
17
開始ページ
1803
終了ページ
1813
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1182/blood-2018-06-857789

Dendritic cells (DCs), which are vital for immune responses, are derived from bone marrow hematopoietic stem cells via common DC progenitors (CDPs). DC lineage fate decisions occurring at stages much earlier than CDPs have recently been recognized, yet the mechanism remains elusive. By single-cell RNA-sequencing, in vivo cell transfer experiments, and an assay for transposase-accessible chromatin sequencing using wild-type, IRF8-GFP chimera knock-in or IRF8-knockout mice, we demonstrate that IRF8 regulates chromatin at the lymphoid-primed multipotent progenitor (LMPP) stage to induce early commitment toward DCs. A low but significant expression of IRF8, a transcription factor essential for DC and monocyte development, was initiated in a subpopulation within LMPPs. These IRF8+ LMPPs were derived from IRF8- LMPPs and predominantly produced DCs, especially classical DC1s, potentially via known progenitors, such as monocyte-DC progenitors, CDPs, and preclassical DCs. IRF8+ LMPPs did not generate significant numbers of monocytes, neutrophils, or lymphocytes. Although IRF8- and IRF8+ LMPPs displayed very similar global gene expression patterns, the chromatin of enhancers near DC lineage genes was more accessible in IRF8+ LMPPs than in IRF8- LMPPs, an epigenetic change dependent on IRF8. The majority of the genes epigenetically primed by IRF8 were still transcriptionally inactive at the LMPP stage, but were highly expressed in the downstream DC lineage populations such as CDPs. Therefore, early expression of the key transcription factor IRF8 changes chromatin states in otherwise multipotent progenitors, biasing their fate decision toward DCs.

リンク情報
DOI
https://doi.org/10.1182/blood-2018-06-857789
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30796024
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484390
ID情報
  • DOI : 10.1182/blood-2018-06-857789
  • ISSN : 0006-4971
  • PubMed ID : 30796024
  • PubMed Central 記事ID : PMC6484390

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