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Capacity of yolk sac macrophages, fetal liver and adult monocytes to colonize an empty niche and develop into functional tissue resident macrophages

ABSTRACT: Tissue-resident macrophages can derive from yolk sac macrophages, fetal liver monocytes or adult bone marrow monocytes. Whether these precursors can give rise to transcriptionally identical alveolar macrophages is unknown. Here, we transferred traceable yolk sac macrophages, fetal liver monocytes, adult bone marrow monocytes or adult alveolar macrophages as a control, into the empty alveolar macrophage niche of neonatal Csf2rb-/- mice. All precursors efficiently colonized the alveolar niche and generated alveolar macrophages that were transcriptionally almost identical, with only 22 genes that could be linked to their origin. Underlining the physiological relevance of our findings, all transfer-derived alveolar macrophages self-maintained within the lungs for up to 1 year and durably prevented alveolar proteinosis. Thus, precursor origin does not affect the development of functional self-maintaining tissue-resident macrophages.

ORGANISM(S): Mus musculus

PROVIDER: GSE76999 | GEO | 2016/03/01

SECONDARY ACCESSION(S): PRJNA309234

REPOSITORIES: GEO

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Capacity of yolk sac macrophages, fetal liver and adult monocytes to colonize an empty niche and develop into functional tissue resident macrophages

Project description:Tissue-resident macrophages can derive from yolk sac macrophages, fetal liver monocytes or adult bone marrow monocytes. Whether these precursors can give rise to transcriptionally identical alveolar macrophages is unknown. Here, we transferred traceable yolk sac macrophages, fetal liver monocytes, adult bone marrow monocytes or adult alveolar macrophages as a control, into the empty alveolar macrophage niche of neonatal Csf2rb-/- mice. All precursors efficiently colonized the alveolar niche and generated alveolar macrophages that were transcriptionally almost identical, with only 22 genes that could be linked to their origin. Underlining the physiological relevance of our findings, all transfer-derived alveolar macrophages self-maintained within the lungs for up to 1 year and durably prevented alveolar proteinosis. Thus, precursor origin does not affect the development of functional self-maintaining tissue-resident macrophages. CD45.1+CD45.2+ yolk sac macrophages, fetal liver monocytes, adult bone marrow monocytes or adult alveolar macrophages from the bronchoalveolar lavage were sorted from wild type CD45.1+CD45.2+ mice of indicated ages. From part of these samples RNA was isolated. The other part was transferred intranasally into the lungs of neonate Csf2rb-/- mice. 6 weeks post-transfer, transfer-derived CD45.1+CD45.2+ alveolar macrophages were sorted from the bronchoalveolar lavage. Wild type CD45.1+CD45.2 alveolar macrophages from the bronchoalveolar lavage of 6 week old mice were sorted as control. 36 samples (arrays) in total. RNA was isolated, amplified with Nugene pico kit, converted to cDNA and then hybridised on Affymetrix GeneChip Mouse Gene 1.0 ST Arrays.

2016-03-01 | E-GEOD-76999 | biostudies-arrayexpress

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. 12 samples of progenitors, monocytes or macrophages are analyzed from 2 to 4 replicate. Each replicate derived from at least 5 embryos or adult mice

2015-04-23 | E-GEOD-66970 | biostudies-arrayexpress

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

2015-04-23 | GSE66970 | GEO

Human induced pluripotent stem cell-derived macrophages share ontogeny with MYB-independent tissue-resident macrophages

Project description:Tissue-resident macrophages such as microglia, Kupffer and Langerhans cells derive from Myb-independent yolk sac (YS) progenitors generated before the emergence of hematopoietic stem cells (HSCs). Myb-independent YS-derived resident macrophages self-renew locally, independently of circulating monocytes and HSCs. In contrast, adult blood monocytes as well as infiltrating, gut and dermal macrophages derive from Myb-dependent HSCs. These findings are derived from the mouse, using gene knock-outs and lineage tracing, but their applicability to human development has not been formally demonstrated. Here we use human induced pluripotent stem cells (iPSCs) as a tool to model human hematopoietic development. By using a CRISPR-Cas9 knock-out strategy we show that human iPSC-derived monocytes/macrophages develop in a MYB-independent, RUNX1 and SPI1 (PU.1)-dependent fashion. This result makes human iPSC-derived macrophages developmentally related to and a good model for MYB-independent tissue-resident macrophages such as alveolar and kidney macrophages, microglia, Kupffer and Langerhans cells.

2017-01-07 | GSE93285 | GEO

Comparative genomic analysis of basal and LPS-induced expression patterns of bone marrow derived macrophages and bone marrow resident macrophages

Project description:Comparative genomic analysis of basal and LPS-induced expression patterns of bone marrow derived macrophages and bone marrow resident macrophages demonstrates completely divergent transcriptome profile and indicates/confirms the existance of two distinct monocyte/macrophage populations in murine bone marrow. Most resident tissue macrophages descent from embryonic precursors of the yolk sac but inflammatory and bone marrow (BM) macrophages are considered to develop from hematopoietic stem cells (HSCs) in the BM. We now identified a novel subpopulation of resident CD163+ macrophages in the BM which were phenotypically and functionally distinct from classical BM-derived macrophages. Bioinformatics analysis of transcriptoms indicated a unique immune-modulatory phenotype of CD163+ macrophages. Cell fate studies in Csf1rMer-iCre-Mer;RosaLSL-GFP mice demonstrated that resident CD163+ macrophages of the BM do not develop from HSCs but descent from embryonic progenitors in the yolk sac strictly dependent on transcription factor IRF8. In contrast to other yolk sac derived tissue macrophages CD163+ cells seem to play a relevant role in infections and sterile inflammation. IRF8-/- mice lacking this population are highly sensible to S. aureus infections. Thus, CD163 defines a macrophage population resident in the bone marrow but originating from yolk sac progenitors which exhibits immune-modulatory properties under different inflammatory conditions. We used quantitative RNA-seq to perform whole transcriptome analysis and compare the transcriptomes of resident CD163+ BM macrophages and classical CD163- BMDM in steady state and after LPS stimulation.

2017-01-31 | GSE92618 | GEO

Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells

Project description:Self-renewing tissue-resident macrophages are thought to be exclusively derived from embryonic progenitors. However, whether circulating monocytes can also give rise to such macrophages has not been formally investigated. Here we use a new model of diphtheria toxin-mediated depletion of liver-resident Kupffer cells to generate niche availability and show that circulating monocytes engrafted in the liver, gradually adopt the transcriptional profile of their depleted counterparts and become long-lived self-renewing cells. Underlining the physiological relevance of our findings, circulating monocytes also contribute to the expanding pool of macrophages in the liver shortly after birth, when macrophage niches become available during normal organ growth. Thus, like embryonic precursors, monocytes can and do give rise to self-renewing tissue-resident macrophages if the niche is available to them. Clec4F+ Kupffer cells were isolated and sorted from livers from adult WT mice or KC-DTR or KC-DTR littermate control mice +/- 50ng DT at indicated timepoints. 19 samples (arrays) in total. RNA was isolated, amplified with Nugene pico kit, converted to cDNA and then hybridised on Affymetrix GeneChip Mouse Gene 1.0 ST Arrays.

2015-11-21 | E-GEOD-75225 | biostudies-arrayexpress

Mus musculus

Project description:Capacity of yolk sac macrophages, fetal liver and adult monocytes to colonize an empty niche and develop into functional tissue resident macrophages

| PRJNA309234 | ENA

Heterogeneous Origins and Functions of Mouse Skeletal Muscle Resident Macrophages

Project description:Tissue resident macrophages can arise from either embryonic or adult hematopoiesis and play important roles in a wide range of biological processes, such as tissue remodeling during organogenesis, tissue homeostasis in the steady state, tissue repair following injury, and immune response to pathogens. Although the origins and tissue-specific functions of resident macrophages have been extensively studied in many other tissues, they are not well characterized in skeletal muscle. In the present study, we have characterized for the first time the ontogeny of skeletal muscle resident macrophages, showing evidence that they arise from both embryonic hematopoietic progenitors, including yolk sac primitive macrophages and fetal liver monocytes, and adult bone marrow hematopoietic stem cells. Single cell-based transcriptome analysis revealed that skeletal muscle resident macrophages were highly distinctive from resident macrophages in other tissues, expressing a specific set of transcription factors and containing functionally diverse subsets correlating to their origins. They appear more active in maintaining tissue homeostasis and promoting muscle growth and regeneration.

2020-07-29 | GSE142480 | GEO

Erythro-myeloid progenitors contribute endothelial cells to developing blood vessels

Project description:The earliest blood vessels in the mammalian embryo are formed when endothelial cells (ECs) differentiate from angioblasts and coalesce into tubular networks. Thereafter, the en-dothelium is thought to expand solely by proliferation of pre-existing ECs. Here we show that the earliest precursors of erythrocytes, megakaryocytes and macrophages, the yolk sac-derived erythro-myeloid progenitors (EMPs), provide a complementary source of ECs that are recruited into pre-existing vasculature. Whereas a first wave of yolk sac-resident EMPs contributes ECs to the yolk sac endothelium, a second wave of EMPs colonises the embryo and contributes ECs to intraembryonic endothelium in multiple organs, where they persist into adulthood. By demonstrating that EMPs constitute a hitherto unrecognised source of ECs, we reveal that embryonic blood vascular endothelium expands in a dual mechanism that involves both the proliferation of pre-existing ECs and the incorporation of ECs derived from hematopoietic precursors.

2018-08-02 | GSE117978 | GEO

Expression data from different types of human alveolar macrophage (AM) precursors

Project description:Despite their importance in lung health and disease, it remains unknown how human alveolar macrophages develop early in life. In this study we identified the fetal progenitor of human alveolar macrophages. We used microarray to define the gene signatures of human CD14+ blood monocytes (adult AM precursors), CD116+CD64+ fetal liver monocytes, and CD116+CD64- fetal AM precursors.

2021-12-08 | GSE190256 | GEO

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