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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

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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

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.

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

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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

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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

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