Transcriptome‐based profiling of yolk sac‐derived macrophages reveals a role for Irf8 in macrophage maturation

Recent studies have shown that tissue macrophages (MΦ) arise from embryonic progenitors of the yolk sac (YS) and fetal liver and colonize tissues before birth. Further studies have proposed that developmentally distinct tissue MΦ can be identified based on the differential expression of F4/80 and CD11b, but whether a characteristic transcriptional profile exists is largely unknown. Here, we took advantage of an inducible fate‐mapping system that facilitated the identification of CD45+c‐kit−CX3CR1+F4/80+ (A2) progenitors of the YS as the source of F4/80hi but not CD11bhi MΦ. Large‐scale transcriptional profiling of MΦ precursors from the YS stage to adulthood allowed for building computational models for F4/80hi tissue macrophages being direct descendants of A2 progenitors. We further identified a distinct molecular signature of F4/80hi and CD11bhi MΦ and found that Irf8 was vital for MΦ maturation. Our data provide new cellular and molecular insights into the origin and developmental pathways of tissue MΦ.

[1]  Y. Saeys,et al.  Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells , 2016, Nature Communications.

[2]  Jianpeng Sheng,et al.  Most Tissue-Resident Macrophages Except Microglia Are Derived from Fetal Hematopoietic Stem Cells. , 2015, Immunity.

[3]  I. Amit,et al.  Host microbiota constantly control maturation and function of microglia in the CNS , 2015, Nature Neuroscience.

[4]  F. Ginhoux,et al.  C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages. , 2015, Immunity.

[5]  W. Talbot,et al.  Differential Requirement for irf8 in Formation of Embryonic and Adult Macrophages in Zebrafish , 2015, PloS one.

[6]  Gérard Eberl,et al.  Liver-resident macrophage necroptosis orchestrates type 1 microbicidal inflammation and type-2-mediated tissue repair during bacterial infection. , 2015, Immunity.

[7]  J. Stender,et al.  Environment Drives Selection and Function of Enhancers Controlling Tissue-Specific Macrophage Identities , 2015, Cell.

[8]  I. Amit,et al.  Tissue-Resident Macrophage Enhancer Landscapes Are Shaped by the Local Microenvironment , 2014, Cell.

[9]  F. Geissmann,et al.  Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors , 2014, Nature.

[10]  N. Rosenthal,et al.  Progressive replacement of embryo-derived cardiac macrophages with age , 2014, The Journal of experimental medicine.

[11]  G. Randolph,et al.  Origin and functions of tissue macrophages. , 2014, Immunity.

[12]  F. Ginhoux,et al.  Monocytes and macrophages: developmental pathways and tissue homeostasis , 2014, Nature Reviews Immunology.

[13]  Marco Prinz,et al.  Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease , 2014, Nature Reviews Neuroscience.

[14]  M. Sieweke,et al.  Beyond Stem Cells: Self-Renewal of Differentiated Macrophages , 2013, Science.

[15]  T. Luedde,et al.  A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation , 2013, Nature Neuroscience.

[16]  F. Rosenbauer,et al.  PU.1 level-directed chromatin structure remodeling at the Irf8 gene drives dendritic cell commitment. , 2013, Cell reports.

[17]  M. Cybulsky,et al.  Faculty Opinions recommendation of Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. , 2013 .

[18]  M. Odenthal,et al.  Intrahepatic myeloid-cell aggregates enable local proliferation of CD8+ T cells and successful immunotherapy against chronic viral liver infection , 2013, Nature Immunology.

[19]  A. Mildner,et al.  Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. , 2013, Immunity.

[20]  F. Rosenbauer,et al.  Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways , 2013, Nature Neuroscience.

[21]  Amin R. Mazloom,et al.  Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages , 2012, Nature Immunology.

[22]  F. Ginhoux,et al.  Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac–derived macrophages , 2012, The Journal of experimental medicine.

[23]  J. Pollard,et al.  A Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells , 2012, Science.

[24]  Damien Chaussabel,et al.  IRF8 mutations and human dendritic-cell immunodeficiency. , 2011, The New England journal of medicine.

[25]  Gary D. Bader,et al.  WordCloud: a Cytoscape plugin to create a visual semantic summary of networks , 2011, Source Code for Biology and Medicine.

[26]  Gary D Bader,et al.  Enrichment Map: A Network-Based Method for Gene-Set Enrichment Visualization and Interpretation , 2010, PloS one.

[27]  F. Ginhoux,et al.  Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages , 2010, Science.

[28]  K. Nieselt,et al.  Mayday - integrative analytics for expression data , 2010, BMC Bioinformatics.

[29]  T. Taniguchi,et al.  The IRF family transcription factors in immunity and oncogenesis. , 2008, Annual review of immunology.

[30]  F. Rossi,et al.  Local self-renewal can sustain CNS microglia maintenance and function throughout adult life , 2007, Nature Neuroscience.

[31]  A. Mildner,et al.  Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions , 2007, Nature Neuroscience.

[32]  Ana Cumano,et al.  Ontogeny of the hematopoietic system. , 2007, Annual review of immunology.

[33]  Daniel G. Tenen,et al.  Transcription factors in myeloid development: balancing differentiation with transformation , 2007, Nature Reviews Immunology.

[34]  Steffen Jung,et al.  Three pathways to mature macrophages in the early mouse yolk sac. , 2005, Blood.

[35]  Martin Kuiper,et al.  BiNGO: a Cytoscape plugin to assess overrepresentation of Gene Ontology categories in Biological Networks , 2005, Bioinform..

[36]  A. Sher,et al.  Analysis of Fractalkine Receptor CX3CR1 Function by Targeted Deletion and Green Fluorescent Protein Reporter Gene Insertion , 2000, Molecular and Cellular Biology.

[37]  Robert V Farese,et al.  Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice. , 1997, The Journal of clinical investigation.

[38]  J. Waring,et al.  Immunodeficiency and Chronic Myelogenous Leukemia-like Syndrome in Mice with a Targeted Mutation of the ICSBP Gene , 1996, Cell.

[39]  A. Feeney,et al.  Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities. , 1996, The EMBO journal.

[40]  Y. Benjamini,et al.  More powerful procedures for multiple significance testing. , 1990, Statistics in medicine.

[41]  R. van Furth,et al.  THE ORIGIN AND KINETICS OF MONONUCLEAR PHAGOCYTES , 1968, The Journal of experimental medicine.

[42]  Ash A. Alizadeh,et al.  SUPPLEMENTARY NOTE , 1879, Botanical Gazette.

[43]  Hua Tang,et al.  Corrigendum: Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice , 2014, Nature Immunology.

[44]  Anton J. Enright,et al.  Network visualization and analysis of gene expression data using BioLayout Express3D , 2009, Nature Protocols.

[45]  K. Ozato,et al.  ICSBP/IRF-8: its regulatory roles in the development of myeloid cells. , 2002, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[46]  B T Grenfell,et al.  Generalized linear modelling for parasitologists. , 1997, Parasitology today.