Project description:Tissue resident macrophages are functionally diverse cells that share an embryonic mesodermal origin. However, the mechanism(s) that control their specification remain unclear. We performed transcriptional, molecular and in situ spatio-temporal analyses of macrophage development in mice. We report that Erythro-Myeloid Progenitors generate pre-macrophages (pMacs) that simultaneously colonize the head and caudal embryo from embryonic day (E)9.5 in a chemokine-receptor dependent manner, to further differentiate into tissue F4/80+ macrophages. The core macrophage transcriptional program initiated in pMacs, is rapidly diversified in early macrophages as expression of transcriptional regulators becomes tissue-specific. For example, the preferential expression of the transcriptional regulator Id3 initiated in early fetal liver macrophages appears critical for Kupffer cell differentiation, as inactivation of Id3 causes a selective Kupffer cell deficiency that persists in adults. We propose that colonization of developing tissues by differentiating macrophages is immediately followed by their specification as they establish residence, hereby generating the macrophage diversity observed in post-natal tissues. RNA-sequencing of sorted macrophage cell populations (Mac) and progenitors (EMP, pMac) from various tissues and collected at different time points, including technical and biological replicates
Project description:Tissue resident macrophages are functionally diverse cells that share an embryonic mesodermal origin. However, the mechanism(s) that control their specification remain unclear. We performed transcriptional, molecular and in situ spatio-temporal analyses of macrophage development in mice. We report that Erythro-Myeloid Progenitors generate pre-macrophages (pMacs) that simultaneously colonize the head and caudal embryo from embryonic day (E)9.5 in a chemokine-receptor dependent manner, to further differentiate into tissue F4/80+ macrophages. The core macrophage transcriptional program initiated in pMacs, is rapidly diversified in early macrophages as expression of transcriptional regulators becomes tissue-specific. For example, the preferential expression of the transcriptional regulator Id3 initiated in early fetal liver macrophages appears critical for Kupffer cell differentiation, as inactivation of Id3 causes a selective Kupffer cell deficiency that persists in adults. We propose that colonization of developing tissues by differentiating macrophages is immediately followed by their specification as they establish residence, hereby generating the macrophage diversity observed in post-natal tissues. RNA-sequencing of sorted macrophage cell populations (Mac) and progenitors (EMP, pMac) from various tissues and collected at different time points, including technical and biological replicates
Project description:Tissue resident macrophages are functionally diverse cells that share an embryonic mesodermal origin. However, the mechanism(s) that control their specification remain unclear. We performed transcriptional, molecular and in situ spatio-temporal analyses of macrophage development in mice. We report that Erythro-Myeloid Progenitors generate pre-macrophages (pMacs) that simultaneously colonize the head and caudal embryo from embryonic day (E)9.5 in a chemokine-receptor dependent manner, to further differentiate into tissue F4/80+ macrophages. The core macrophage transcriptional program initiated in pMacs, is rapidly diversified in early macrophages as expression of transcriptional regulators becomes tissue-specific. For example, the preferential expression of the transcriptional regulator Id3 initiated in early fetal liver macrophages appears critical for Kupffer cell differentiation, as inactivation of Id3 causes a selective Kupffer cell deficiency that persists in adults. We propose that colonization of developing tissues by differentiating macrophages is immediately followed by their specification as they establish residence, hereby generating the macrophage diversity observed in post-natal tissues. RNA-sequencing of ID3+/- and ID3-/- Kupffer cells
Project description:Tissue resident macrophages are functionally diverse cells that share an embryonic mesodermal origin. However, the mechanism(s) that control their specification remain unclear. We performed transcriptional, molecular and in situ spatio-temporal analyses of macrophage development in mice. We report that Erythro-Myeloid Progenitors generate pre-macrophages (pMacs) that simultaneously colonize the head and caudal embryo from embryonic day (E)9.5 in a chemokine-receptor dependent manner, to further differentiate into tissue F4/80+ macrophages. The core macrophage transcriptional program initiated in pMacs, is rapidly diversified in early macrophages as expression of transcriptional regulators becomes tissue-specific. For example, the preferential expression of the transcriptional regulator Id3 initiated in early fetal liver macrophages appears critical for Kupffer cell differentiation, as inactivation of Id3 causes a selective Kupffer cell deficiency that persists in adults. We propose that colonization of developing tissues by differentiating macrophages is immediately followed by their specification as they establish residence, hereby generating the macrophage diversity observed in post-natal tissues.
Project description:Tissue resident macrophages are functionally diverse cells that share an embryonic mesodermal origin. However, the mechanism(s) that control their specification remain unclear. We performed transcriptional, molecular and in situ spatio-temporal analyses of macrophage development in mice. We report that Erythro-Myeloid Progenitors generate pre-macrophages (pMacs) that simultaneously colonize the head and caudal embryo from embryonic day (E)9.5 in a chemokine-receptor dependent manner, to further differentiate into tissue F4/80+ macrophages. The core macrophage transcriptional program initiated in pMacs, is rapidly diversified in early macrophages as expression of transcriptional regulators becomes tissue-specific. For example, the preferential expression of the transcriptional regulator Id3 initiated in early fetal liver macrophages appears critical for Kupffer cell differentiation, as inactivation of Id3 causes a selective Kupffer cell deficiency that persists in adults. We propose that colonization of developing tissues by differentiating macrophages is immediately followed by their specification as they establish residence, hereby generating the macrophage diversity observed in post-natal tissues.
Project description:Tissue resident macrophages are functionally diverse cells that share an embryonic mesodermal origin. However, the mechanism(s) that control their specification remain unclear. We performed transcriptional, molecular and in situ spatio-temporal analyses of macrophage development in mice. We report that Erythro-Myeloid Progenitors generate pre-macrophages (pMacs) that simultaneously colonize the head and caudal embryo from embryonic day (E)9.5 in a chemokine-receptor dependent manner, to further differentiate into tissue F4/80+ macrophages. The core macrophage transcriptional program initiated in pMacs, is rapidly diversified in early macrophages as expression of transcriptional regulators becomes tissue-specific. For example, the preferential expression of the transcriptional regulator Id3 initiated in early fetal liver macrophages appears critical for Kupffer cell differentiation, as inactivation of Id3 causes a selective Kupffer cell deficiency that persists in adults. We propose that colonization of developing tissues by differentiating macrophages is immediately followed by their specification as they establish residence, hereby generating the macrophage diversity observed in post-natal tissues.
Project description:Genes expression in Ly6C+/F4/80+ inflammatory macrophages, CX3CR1+/F4/80+ tissue resident macrophages and Ly6G+/F4/80- neutrophils which were isolated from day 3 wounds in C57/B6 mice aged 8 weeks by cell sorting Ly6C+ macrophages expressed higher (over 5 folds) levels of 241 genes compared to CX3CR1+ macrophages, and 3382 genes compared to neutrophils
Project description:Macrophages are hematopoietic cells critical for innate immune defense, but also control organ homeostasis in a tissue-specific manner. Tissue-resident macrophages, therefore, provide a well-defined model to study the impact of ontogeny and microenvironment on chromatin state. Here, we profile the dynamics of four histone modifications across seven tissue-resident macrophage populations, as well as monocytes and neutrophils. We identify 12,743 macrophage-specific enhancers and establish that tissue-resident macrophages have distinct enhancer landscapes. Our work suggests that a combination of tissue and lineage-specific transcription factors form the regulatory networks controlling chromatin specification in tissue-resident macrophages. The environment has the capacity to alter the chromatin landscape of macrophages derived from transplanted adult bone marrow in vivo and even differentiated macrophages are reprogrammed when transferred into a new tissue. Altogether, these data provide a comprehensive view of macrophage regulation and highlight the importance of microenvironment along with pioneer factors in orchestrating macrophage identity and plasticity. 7 tissue-resident macrophage populations were isolated, as well as monocytes and neutrophils, and transcriptome analysis was performed. Experiment was done in duplicates.
Project description:microRNA transcriptome data from wild type and Gata6-deficient tissue resident peritoneal macrophages. 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. Gata6 itself has been shown to be a target of multiple miR. However, microRNA transcriptome and its dependence on tissue-specific macrophage programming, such as effected by GATA6, has not been explored. We used microRNA sequencing to determine the patterns of microRNA expression in peritoneal resident macrophages at homeostasis in the absence of GATA-6 against wild type.