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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE75225 | GEO | 2015/11/21

SECONDARY ACCESSION(S): PRJNA302849

REPOSITORIES: GEO

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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

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

2016-03-01 | GSE76999 | GEO

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

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 of mouse alveolar macrophages sorted from CD11cCre/+ Tgfbr2fl/fl and control Tgfbr2fl/fl neonatal mice

Project description:Alveolar macrophages (AMs) are lung resident phagocytes. They derive from fetal liver monocytes, which colonize the lung during embryonic development and give rise to fully mature AMs perinatally. We have identified TGF- signaling as an indispensible regulator during this process. To analyze the impact of TGF- on the entire transcriptome of AMs, we performed RNA-seq on AMs deficient of Tgfbr2 in CD11cCre/+ Tgfbr2fl/fl mice at P3 with Tgfbr2fl/fl littermates as a control.

2017-11-08 | E-MTAB-6028 | biostudies-arrayexpress

Mus musculus

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

| PRJNA302849 | ENA

Expression data from wild type and Gata6-deficient tissue resident peritoneal macrophages

Project description:Tissue resident macrophages are notoriously heterogeneous, exhibiting discrete phenotypes as a consequence of tissue- and micro-anatomical niche-specific functions, but the molecular basis for this is not understood. We resolved a restricted transcriptional profile for the self-renewing population of peritoneal resident macrophages, which is expressed during homeostasis and inflammation and distinct from other MM-CM-^X. Prominent within this profile was the expression of Gata6. This study represents a characterisation of the role of Gata6 in peritoneal resident macrophage phenotype. We used microarrays to determine the patterns of gene expression in peritoneal resident MM-CM-^X in the absence of GATA-6 against wild type. Conditional 'floxed' Gata6 deficient sex-matched mice between 7 weeks old were compared against wild type

2014-05-09 | E-GEOD-47049 | biostudies-arrayexpress

DPPIV+ fibro-adipogenic progenitors form the niche of adult skeletal muscle self-renewing resident macrophages

Project description:Depending on the tissue, adult tissue-resident macrophages (RMs) are either maintained by blood monocytes or through self-renewal at steady state. While the presence of a nurturing-niche is likely crucial to support the survival and function of self-renewing RMs, evidence regarding its nature is limited. Here, we aimed to characterize the niche for skeletal muscle RMs. We found stromal cells called Fibro-Adipogenic Progenitors (FAPs) to be the main source of colony-stimulating factor 1 (CSF1) in resting skeletal muscle. By utilizing parabiosis in combination with transgenic lines that deplete FAPs (PdgfrαCreERT2 ´ DTA) or conditionally delete FAP-derived CSF1 (PdgfrαCreERT2 ´ Csf1flox/null), we showed that local CSF1 from FAPs is required for the survival of both TIM4- monocyte-derived and TIM4+ self-renewing RMs at steady state in adult skeletal muscle. Following pharmacological depletion of RMs, local CSF1 increases significantly to facilitate their replenishment. Indeed, TIM4- RMs get replaced by blood monocytes following depletion and their numbers increase significantly beyond the normal levels. While a noticeable fraction of TIM4+ RMs also gets replaced by blood monocytes following depletion, their numbers are tightly controlled, which indicates the presence of regulatory mechanisms exclusive to TIM4+ cells. The spatial distribution and number of TIM4+ RMs match with a subpopulation of Dipeptidyl peptidase IV (DPPIV)+ FAPs, suggesting their role as nurturing CSF1-producing niche cells for self-renewing RMs. This finding offers novel opportunities to precisely manipulate the function of self-renewing RMs in situ to further unravel their role in health and disease.

2023-10-24 | GSE241832 | GEO

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

Defining Murine Monocyte Differentiation into Colonic and Ileal Macrophages

Project description:Monocytes are circulating short-lived macrophage precursors that are recruited on demand from the blood to sites of inflammation and challenge. In steady state, classical monocytes give rise to vasculature-resident cells that patrol the luminal side of the endothelium. In addition, classical monocytes feed macrophage compartments of selected organs, including barrier tissues, such as the skin and intestine, as well as the heart. Monocyte differentiation under conditions of inflammation has been studied in considerable detail. In contrast, monocyte differentiation under non-inflammatory conditions remains less well understood. Here we took advantage of a combination of cell ablation and precursor engraftment to investigate the generation of gut macrophages from monocytes. Collectively, we identify factors associated with the gradual adaptation of monocytes to tissue residency. Moreover, comparison of monocyte differentiation into the colon and ileum-resident macrophages revealed the graduated acquisition of gut segment-specific gene expression signatures.

2020-01-01 | GSE140919 | GEO

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