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

Blood
Daisuke KurotakiTomohiko Tamura

Abstract

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 i...Continue Reading

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Citations

Apr 27, 2019·Blood·Martin Guilliams, Charlotte L Scott
May 1, 2019·Cancers·Maria Rosaria SapienzaStefano Pileri
Aug 14, 2019·Nature Immunology·Martin Guilliams, Tomohiko Tamura
Sep 11, 2020·Nature Reviews. Immunology·David A AndersonKenneth M Murphy
Sep 6, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cindy Audiger, Sylvie Lesage
Dec 9, 2020·Nature Metabolism·Masayuki TsukasakiHiroshi Takayanagi
Aug 18, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Amitabh DasVivek Thumbigere-Math
Apr 4, 2021·Science Immunology·Shengbo ZhangStephen L Nutt
Oct 31, 2020·Molecular Immunology·Heike Chauvistré, Kristin Seré
Jun 20, 2020·Immunity·Stephen L Nutt, Michaël Chopin
Jun 17, 2021·International Immunology·Toshiaki OhtekiNobuyuki Onai
Sep 5, 2021·Cellular & Molecular Immunology·Theresa L Murphy, Kenneth M Murphy
Nov 26, 2021·Immunological Reviews·Zewen Kelvin TuongMenna R Clatworthy

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