Specification of tissue-resident macrophages during organogenesis

Abstract

Resident macrophages support embryonic development and tissue homeostasis and repair. The mechanisms that control their differentiation remain unclear. We report here that Erythro-Myeloid Progenitors generate pre-macrophages (pMacs) that simultaneously colonize the whole embryo from embryonic day (E)9.5 in a chemokine-receptor dependent manner. The core macrophage program initiated in pMacs is rapidly diversified as expression of transcriptional regulators becomes tissue-specific in early macrophages. This process appears essential for macrophage specification and maintenance, as inactivation of Id3 impairs the development of liver macrophages and results in selective Kupffer cell deficiency in adults. We propose that macrophage differentiation is an integral part of organogenesis as colonization of organ anlagen by pMacs is followed by their specification into tissue macrophages, hereby generating the macrophage diversity observed in postnatal tissues.

Thyroid hormone metabolism in innate immune cells

“…Until recently, these were thought to be continuously replenished from the circulating monocyte pool. Tissue-resident macrophages are now known to be derived from embryonic precursors that colonize the tissues prenatally (Mass et al 2016). These cells, which include Kupffer cells and microglia, are also able to maintain their populations in adult tissues due to local cell proliferation independently of circulating monocytes (Hashimoto et al 2013, Ginhoux & Jung 2014, Mass et al 2016.…”

“…Tissue-resident macrophages are now known to be derived from embryonic precursors that colonize the tissues prenatally (Mass et al 2016). These cells, which include Kupffer cells and microglia, are also able to maintain their populations in adult tissues due to local cell proliferation independently of circulating monocytes (Hashimoto et al 2013, Ginhoux & Jung 2014, Mass et al 2016. The various tissue-resident macrophages comprise distinct cell populations whose phenotype differs strongly between tissues (Murray & Wynn 2011).…”

“…Microglia Microglia are the resident macrophages of the central nervous system and are derived from myeloid progenitor cells that migrate to the brain during foetal development (Mass et al 2016). Due to the neurological phenotype associated with mutations in TH transporters, intracellular TH metabolism in brain cells has been assessed in detail.…”

Understanding development and stem cells using single cell-based analyses of gene expression

“…One of the most powerful outcomes of these methods is the identification of signaling pathways and genetic circuits that contribute to cell state transitions, which thereby generates specific and testable hypotheses. Some notable and recent examples of applying pseudotime analytics to diverse developmental contexts include the specification of human mesoderm (Loh et al, 2016) and endoderm (Chu et al, 2016) derivatives from pluripotent stem cells, and the specification of tissue-resident macrophages from erythroid-myeloid progenitors (Mass et al, 2016). Here, we discuss the application of temporal inference, or pseudotime, methods to explore the progression of quiescent neural stem cells (NSCs) to neurons.…”

Gene regulatory mechanisms underlying the intestinal innate immune response

“…In the steady state, they arise from two distinct sources: first, continuously recruited from circulating monocytes in the gut [10], the dermis [11] and the heart [12], and second, from fetal monocytes and yolk sac precursors that colonize the whole embryo between E8.5 and E10.5, becoming self-renewal differentiated tissue-resident macrophages [13,14,15 ]. Similar to other systems such as mammalian forebrain, heart and liver [16] as well as cells that arise from hematopoiesis [17 ], macrophage development involves substantial reorganization of the chromatin landscape [6 ,7 ].…”