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Transcriptome-based profiling reveals a macrophage pedigree and identifies Irf8 as pivotal for macrophage homeostasis and function

ABSTRACT: Recent studies have shown that tissue macrophages (MF) arise from embryonic progenitors of the yolk sac (YS) and fetal liver and colonize the tissues before birth. Further studies have proposed that developmentally distinct tissue MF 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 established an inducible fate mapping system that facilitated the identification of A2 progenitors of the YS as source of F4/80hi but not CD11bhi MF. Large-scale transcriptional profiling of MF precursors from the YS until adulthood allowed the description of a complex MF pedigree. We further identified a distinct molecular signature of F4/80hi and CD11bhi MF and found that Irf8 was vital for MF maturation and the innate immune response. Our data provide new cellular and molecular insights into the origin and developmental pathways of tissue MF.

ORGANISM(S): Mus musculus

PROVIDER: GSE73125 | GEO | 2016/07/28

SECONDARY ACCESSION(S): PRJNA296084

REPOSITORIES: GEO

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Transcriptome-based profiling reveals a macrophage pedigree and identifies Irf8 as pivotal for macrophage homeostasis and function

Project description:Recent studies have shown that tissue macrophages (MF) arise from embryonic progenitors of the yolk sac (YS) and fetal liver and colonize the tissues before birth. Further studies have proposed that developmentally distinct tissue MF 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 established an inducible fate mapping system that facilitated the identification of A2 progenitors of the YS as source of F4/80hi but not CD11bhi MF. Large-scale transcriptional profiling of MF precursors from the YS until adulthood allowed the description of a complex MF pedigree. We further identified a distinct molecular signature of F4/80hi and CD11bhi MF and found that Irf8 was vital for MF maturation and the innate immune response. Our data provide new cellular and molecular insights into the origin and developmental pathways of tissue MF. All samples are from mouse tissue at early developmental stages (E8, E9.5, E14) and from adulthood (6 weeks old). For the early developmental time points timed matings were performed. Macrophage populations were isolated from each tissue. RNA was isolated using Arcturus PicoPure isolation kit from yolk sac, brain, liver, kidney and skin samples after FACS sorting. Three replicates per cell population were included. Wildtype and Irf8 knockout samples were analyzed.

2016-07-28 | E-GEOD-73125 | biostudies-arrayexpress

RNAseq of renal dendritic cells from adult Clec9a-Cre Rosa-YFP mice

Project description:We use bulk RNA sequencing of sorted cells to characterize the gene expression profiles of renal dendritic cell (DC) subsets, cDC1 and cDC2, as well as MHCII+CD64+ F4/80hi and MHCII+CD64+ CD11bhi cells. Splenic DCs and red pulp macrophages serve as reference populations for a macrophage-like or DC-like phenotype. By sorting YFP+/YFP- F4/80hi or YFP+/YFP- CD11bhi cells from Clec9a-Cre Rosa-YFP mice we aim to reveal transcriptional differences between YFP-labelled and unlabelled cells. We showed that F4/80hi cells resemble macrophages on a transcriptional level, despite their DC origin, and that renal CD11bhi cells are a transcriptionally unique subset. However, we were not able to reveal differences between YFP+ and YFP- populations.

2020-01-31 | GSE131751 | GEO

Critical Role of Synovial Tissue-resident Macrophage Niche in Joint Homeostasis and Suppression of Chronic Inflammation

Project description:During synovial tissue homeostasis, both monocyte-derived F4/80int, and self-renewing F4/80hi tissue-resident, macrophage populations were identified. In contrast, in HUPO mice, decreased synovial tissue-resident macrophages preceded chronic arthritis, opened a niche permitting the influx of activated monocytes, which differentiated into F4/80hi macrophages.

2021-01-13 | GSE158446 | GEO

RNA-seq analysis of gene expression in macrophages progenitors from the yolk sac of murine embryos at embryonic days 9 and 10, and the modifications resulting from a defective expression of the transcription factor Lyl-1

Project description:Most resident macrophages (MF) populations in adult tissues arise from MF progenitors populations that emerge during ontogeny, either from haematopoietic stem cells (HSC), or from Yolk Sac (YS) progenitors produced prior to HSC development. The YS generates two populations of MF progenitors. In the earliest one, called primitive, MF progenitors arise from monopotent/uni-lineage progenitors, while in the second one they derive from multipotent erythro-myeloid progenitors. These two populations soon mix in the blood circulation, and as they are highly similar in phenotype, the specific features and function of the two MF progenitors populations are still unclear. When investigating the function of the bHLH transcription factor Lyl-1 during the development of blood cells in mouse embryos, we observed that Lyl-1 expression marks YS primitive MF progenitors. Lyl-1 bHLH disruption leads to an increased production and a defective differentiation of primitive MF progenitors. To gain a better insight into primitive MF progenitors specificity and function, we performed a RNA-seq analysis of these progenitors sorted from the YS at embryonic day (E) 9, when the YS only contains primitive MF progenitors, and at E10, when it contains both primitive MF progenitors and those produced by erythro-myeloid progenitors. At both stages, MF progenitors were collected from the YS of either wild-type or Lyl-1-deficient embryos, to better understand the role of Lyl-1 in the development of Lyl-1-expressing resident macrophage populations.

2020-12-31 | E-MTAB-9618 | biostudies-arrayexpress

Murine macrophages: Peritoneal exudate macrophages (PECs) vs tumor-associated macrophages (TAMs)

Project description:Transcriptional landscape of two different TAMs subsets (F4/80hi and F4/80lo) FACS-sorted from fibrosarcoma-bearing WT mice in comparison with control macrophages (PEC)

2021-04-01 | GSE167413 | GEO

RNAseq of renal CD64+CD11b+F4/80hi from adult mice after cisplatin-induced acute kidney injury

Project description:We use bulk RNA sequencing of sorted cells to characterize the gene expression profiles of renal MHCII+/-D11b+F4/80hi cells 72 hours after cisplatin-induced acute kidney injury (AKI). F4/80hi cells are activated after cisplatin induced AKI and start to downregulate MHCII on transcriptional level. Downregulation of MHCII is probably caused by a downregulation/inhibition of its most important transcriptional activator Ciita

2020-01-31 | GSE135921 | GEO

Induced pluripotent stem cell-derived primitive macrophages as a cellular platform to model tissue-resident macrophage differentiation and function

Project description:Specialized tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that migrate into developing tissues and terminally differentiate in situ. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMac) can terminally differentiate into specialized macrophages using growth factors and organ-specific cues. Co-culturing murine iMac with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMac differentiated in vivo into microglia following injection into the brain, and functional alveolar macrophages after engraftment in the lung.

2017-07-20 | GSE99078 | GEO

chimpanzee pedigree sequencing

Project description:Whole genome sequencing of an extended Western chimpanzee pedigree

| PRJEB5937 | ENA

C-Myb+ erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages

Project description:Although classified as hematopoietic cells, tissue-resident macrophages are selfrenewing and maintained independently of adult hematopoiesis. While most macrophages originate from embryonic precursors that seed tissues prior to birth, their exact origin is unknown. Using an in utero macrophage depletion strategy and fatemapping of yolk sac (YS) and fetal liver (FL) hematopoiesis, we found that YS macrophages are the main precursors of microglia, while most other macrophages derive from fetal monocytes. Both YS macrophages and fetal monocytes arise from erythro-myeloid progenitors (EMP) generated in the YS. In the YS, EMP gave rise to macrophages without monocytic intermediates, while EMP seeding the FL upon the establishment of blood circulation acquired c-Myb expression and gave rise to fetal monocytes that then seed embryonic tissues to differentiate into macrophages. Thus, adult tissue-resident macrophages established from HSC-independent embryonic precursors arise from two different developmental programs.

2015-04-23 | GSE66970 | GEO

Tissue macrophage subsets derived from regenerating muscle

Project description:Muscle injury was elicited by cardiotoxin injection into the tibialis anterior muscle. Macrophages were isolated 2 days post-injury from the regenerating muscle. We used microarray to obtain global gene expression data of muscle-derived tissue macrophage subsets. Tissue macrophages were collected from regenerating muscle samples of three animals, Ly6C+ F4/80low and Ly6C- F4/80high macrophage subsets were sorted. The global gene expression patterns of distinct macrophage subsets were analyzed on Affymetrix microarrays.

2014-01-02 | E-GEOD-44057 | biostudies-arrayexpress

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