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Ontogeny of Tissue-Resident Macrophages.

Hoeffel G, Ginhoux F - Front Immunol (2015)

Bottom Line: The origin of tissue-resident macrophages, crucial for homeostasis and immunity, has remained controversial until recently.These tissue-resident macrophages derive from sequential seeding of tissues by two precursors during embryonic development.Thus, hematopoietic stem cell-independent embryonic precursors transiently present in the YS and the FL give rise to long-lasting self-renewing macrophage populations.

View Article: PubMed Central - PubMed

Affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR) , Singapore , Singapore.

ABSTRACT
The origin of tissue-resident macrophages, crucial for homeostasis and immunity, has remained controversial until recently. Originally described as part of the mononuclear phagocyte system, macrophages were long thought to derive solely from adult blood circulating monocytes. However, accumulating evidence now shows that certain macrophage populations are in fact independent from monocyte and even from adult bone marrow hematopoiesis. These tissue-resident macrophages derive from sequential seeding of tissues by two precursors during embryonic development. Primitive macrophages generated in the yolk sac (YS) from early erythro-myeloid progenitors (EMPs), independently of the transcription factor c-Myb and bypassing monocytic intermediates, first give rise to microglia. Later, fetal monocytes, generated from c-Myb(+) EMPs that initially seed the fetal liver (FL), then give rise to the majority of other adult macrophages. Thus, hematopoietic stem cell-independent embryonic precursors transiently present in the YS and the FL give rise to long-lasting self-renewing macrophage populations.

No MeSH data available.


Related in: MedlinePlus

Fetal monopoiesis and macrophage ontogeny. At E8.5 as the blood circulation is established, the YS HE, possibly in conjunction with other hemogenic sites, generates EMPs expressing CD41 and c-Myb. These late EMPs seed the fetal liver around E9.5 where they expand rapidly to give rise to CSF-1R+ myeloid progenitors that are able to generate fetal monocytes through cMoP intermediates at E12.5. Fetal monocytes then spread via the blood circulation to all tissues, with the exception of the brain, which is isolated by the establishment of the blood–brain barrier at approximately E13.5. In the tissues, fetal monocytes begin to differentiate into macrophages, progressively outnumbering the previously established primitive macrophages. These fetal monocyte-derived macrophages maintain the capacity to self-renew throughout adulthood in certain tissues, such as the liver or the lung, where they will not be replaced by adult BM-derived monocytes.
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Figure 3: Fetal monopoiesis and macrophage ontogeny. At E8.5 as the blood circulation is established, the YS HE, possibly in conjunction with other hemogenic sites, generates EMPs expressing CD41 and c-Myb. These late EMPs seed the fetal liver around E9.5 where they expand rapidly to give rise to CSF-1R+ myeloid progenitors that are able to generate fetal monocytes through cMoP intermediates at E12.5. Fetal monocytes then spread via the blood circulation to all tissues, with the exception of the brain, which is isolated by the establishment of the blood–brain barrier at approximately E13.5. In the tissues, fetal monocytes begin to differentiate into macrophages, progressively outnumbering the previously established primitive macrophages. These fetal monocyte-derived macrophages maintain the capacity to self-renew throughout adulthood in certain tissues, such as the liver or the lung, where they will not be replaced by adult BM-derived monocytes.

Mentions: The quest to elucidate the origins of embryonic HSCs led to the discovery of earlier lineage-restricted HSC-independent progenitors seeding the FL at E10.5. These progenitors arise concurrently with the transition of primitive to definitive erythropoiesis and were thus considered to form a transient stage of definitive hematopoiesis (45, 47, 55). Transient definitive hematopoiesis consists of progenitors sequentially acquiring myeloid, then lymphoid potential, without exhibiting the long-term reconstitution potential of HSCs. Seminal work from Palis and colleagues on embryonic erythropoiesis in the YS described the parallel emergence of multiple myeloid lineage potential progenitors from E8.25 in the YS (45). Palis et al. first observed the emergence of definitive progenitors for mast cells and a bipotential granulocyte/macrophage progenitor. These progenitors then migrated to the FL through the bloodstream after E8.5, once circulation was established (44, 56). From this pattern of development, the authors concluded that definitive hematopoietic progenitors arise in the YS, migrate through the bloodstream, and seed the FL to rapidly initiate the first phase of intra-embryonic hematopoiesis. Similarly, primitive and definitive erythropoiesis, associated with myelopoiesis, was also shown to emerge prior to HSC in the zebrafish embryo (57). Bertrand et al. showed that definitive hematopoiesis initiates in the posterior blood island with only transient proliferative potential. Because these HSC-independent definitive progenitors were observed to produce definitive erythroid and myeloid cell types, but not to colonize the zebrafish thymus (implying that they are devoid of lymphoid potential), this population was termed EMPs (57). Interestingly, EMPs can also emerge from the hemogenic endothelium (HE) located in the placenta and umbilical cord (58) and colonize the FL from E9.5 (55) to participate in definitive hematopoiesis. Further studies advanced the field significantly by identifying CD41 as an early marker (pre-CD45) for defining hematopoietic progenitors, including EMPs, emerging from the YS (59, 60). Altogether, these important studies provided phenotypic and functional analyses of the first hematopoietic progenitors and demonstrated that definitive hematopoiesis proceeds through two distinct waves during embryonic development (Figure 3).


Ontogeny of Tissue-Resident Macrophages.

Hoeffel G, Ginhoux F - Front Immunol (2015)

Fetal monopoiesis and macrophage ontogeny. At E8.5 as the blood circulation is established, the YS HE, possibly in conjunction with other hemogenic sites, generates EMPs expressing CD41 and c-Myb. These late EMPs seed the fetal liver around E9.5 where they expand rapidly to give rise to CSF-1R+ myeloid progenitors that are able to generate fetal monocytes through cMoP intermediates at E12.5. Fetal monocytes then spread via the blood circulation to all tissues, with the exception of the brain, which is isolated by the establishment of the blood–brain barrier at approximately E13.5. In the tissues, fetal monocytes begin to differentiate into macrophages, progressively outnumbering the previously established primitive macrophages. These fetal monocyte-derived macrophages maintain the capacity to self-renew throughout adulthood in certain tissues, such as the liver or the lung, where they will not be replaced by adult BM-derived monocytes.
© Copyright Policy
Related In: Results  -  Collection

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Figure 3: Fetal monopoiesis and macrophage ontogeny. At E8.5 as the blood circulation is established, the YS HE, possibly in conjunction with other hemogenic sites, generates EMPs expressing CD41 and c-Myb. These late EMPs seed the fetal liver around E9.5 where they expand rapidly to give rise to CSF-1R+ myeloid progenitors that are able to generate fetal monocytes through cMoP intermediates at E12.5. Fetal monocytes then spread via the blood circulation to all tissues, with the exception of the brain, which is isolated by the establishment of the blood–brain barrier at approximately E13.5. In the tissues, fetal monocytes begin to differentiate into macrophages, progressively outnumbering the previously established primitive macrophages. These fetal monocyte-derived macrophages maintain the capacity to self-renew throughout adulthood in certain tissues, such as the liver or the lung, where they will not be replaced by adult BM-derived monocytes.
Mentions: The quest to elucidate the origins of embryonic HSCs led to the discovery of earlier lineage-restricted HSC-independent progenitors seeding the FL at E10.5. These progenitors arise concurrently with the transition of primitive to definitive erythropoiesis and were thus considered to form a transient stage of definitive hematopoiesis (45, 47, 55). Transient definitive hematopoiesis consists of progenitors sequentially acquiring myeloid, then lymphoid potential, without exhibiting the long-term reconstitution potential of HSCs. Seminal work from Palis and colleagues on embryonic erythropoiesis in the YS described the parallel emergence of multiple myeloid lineage potential progenitors from E8.25 in the YS (45). Palis et al. first observed the emergence of definitive progenitors for mast cells and a bipotential granulocyte/macrophage progenitor. These progenitors then migrated to the FL through the bloodstream after E8.5, once circulation was established (44, 56). From this pattern of development, the authors concluded that definitive hematopoietic progenitors arise in the YS, migrate through the bloodstream, and seed the FL to rapidly initiate the first phase of intra-embryonic hematopoiesis. Similarly, primitive and definitive erythropoiesis, associated with myelopoiesis, was also shown to emerge prior to HSC in the zebrafish embryo (57). Bertrand et al. showed that definitive hematopoiesis initiates in the posterior blood island with only transient proliferative potential. Because these HSC-independent definitive progenitors were observed to produce definitive erythroid and myeloid cell types, but not to colonize the zebrafish thymus (implying that they are devoid of lymphoid potential), this population was termed EMPs (57). Interestingly, EMPs can also emerge from the hemogenic endothelium (HE) located in the placenta and umbilical cord (58) and colonize the FL from E9.5 (55) to participate in definitive hematopoiesis. Further studies advanced the field significantly by identifying CD41 as an early marker (pre-CD45) for defining hematopoietic progenitors, including EMPs, emerging from the YS (59, 60). Altogether, these important studies provided phenotypic and functional analyses of the first hematopoietic progenitors and demonstrated that definitive hematopoiesis proceeds through two distinct waves during embryonic development (Figure 3).

Bottom Line: The origin of tissue-resident macrophages, crucial for homeostasis and immunity, has remained controversial until recently.These tissue-resident macrophages derive from sequential seeding of tissues by two precursors during embryonic development.Thus, hematopoietic stem cell-independent embryonic precursors transiently present in the YS and the FL give rise to long-lasting self-renewing macrophage populations.

View Article: PubMed Central - PubMed

Affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR) , Singapore , Singapore.

ABSTRACT
The origin of tissue-resident macrophages, crucial for homeostasis and immunity, has remained controversial until recently. Originally described as part of the mononuclear phagocyte system, macrophages were long thought to derive solely from adult blood circulating monocytes. However, accumulating evidence now shows that certain macrophage populations are in fact independent from monocyte and even from adult bone marrow hematopoiesis. These tissue-resident macrophages derive from sequential seeding of tissues by two precursors during embryonic development. Primitive macrophages generated in the yolk sac (YS) from early erythro-myeloid progenitors (EMPs), independently of the transcription factor c-Myb and bypassing monocytic intermediates, first give rise to microglia. Later, fetal monocytes, generated from c-Myb(+) EMPs that initially seed the fetal liver (FL), then give rise to the majority of other adult macrophages. Thus, hematopoietic stem cell-independent embryonic precursors transiently present in the YS and the FL give rise to long-lasting self-renewing macrophage populations.

No MeSH data available.


Related in: MedlinePlus