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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

Primitive hematopoiesis and yolk sac macrophage ontogeny. Early EMPs emerge in the YS around E7.5 before establishment of the blood circulation. They express CD41 and CSF-1R and are independent of the transcription factor C-Myb. Upon establishment of the blood circulation around E8.5, EMPs differentiate into primitive macrophages as well as primitive erythrocytes and granulocytes. Primitive macrophages seed all fetal tissues, in particular the head where they will give rise to future brain microglia that are able to continuously self-renew throughout adulthood. EMPs seeding the fetal liver briefly expand to generate a local macrophage population, likely important for sustaining enucleation of primitive erythrocytes passing through the sinusoid prior to the establishment of definitive hematopoiesis and the generation of fetal monocyte-derived macrophages in the fetal liver.
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Figure 2: Primitive hematopoiesis and yolk sac macrophage ontogeny. Early EMPs emerge in the YS around E7.5 before establishment of the blood circulation. They express CD41 and CSF-1R and are independent of the transcription factor C-Myb. Upon establishment of the blood circulation around E8.5, EMPs differentiate into primitive macrophages as well as primitive erythrocytes and granulocytes. Primitive macrophages seed all fetal tissues, in particular the head where they will give rise to future brain microglia that are able to continuously self-renew throughout adulthood. EMPs seeding the fetal liver briefly expand to generate a local macrophage population, likely important for sustaining enucleation of primitive erythrocytes passing through the sinusoid prior to the establishment of definitive hematopoiesis and the generation of fetal monocyte-derived macrophages in the fetal liver.

Mentions: In mice, the first hematopoietic progenitors appear in the extra-embryonic YS blood islands at around embryonic age 7.25 (E7.25), where primitive hematopoiesis is initiated, producing mainly nucleated erythrocytes. This observation linked the myeloid progenitors observed in the YS at E7 with the emergence of YS macrophages after E9.0 [Figure 2; Ref. (42–45)]. Primitive hematopoiesis was also shown to produce megakaryocyte progenitors (46). The denomination “primitive” was given to reflect the production of embryonic erythroblasts, like those observed in lower species such as fish, amphibians, and birds, and remaining nucleated throughout their life span (47–49). This denomination was extended to macrophages in the YS due to their concomitant development prior to FL hematopoiesis. Interestingly, no clear evidence of monocytic intermediates was reported at this stage, although the seminal study of Cline and Moore did mention the existence of local intermediate cells between progenitors and functional macrophages (43). Studies by Naito and Takahashi et al. clarified the emergence of primitive macrophages in the YS blood islands in the mouse and rat, observing an absence of endogenous peroxidase activity as a surrogate marker for an absence of monocytic intermediates, such as those found in the BM (50–52), suggesting a unique developmental pathway for YS macrophages (53, 54).


Ontogeny of Tissue-Resident Macrophages.

Hoeffel G, Ginhoux F - Front Immunol (2015)

Primitive hematopoiesis and yolk sac macrophage ontogeny. Early EMPs emerge in the YS around E7.5 before establishment of the blood circulation. They express CD41 and CSF-1R and are independent of the transcription factor C-Myb. Upon establishment of the blood circulation around E8.5, EMPs differentiate into primitive macrophages as well as primitive erythrocytes and granulocytes. Primitive macrophages seed all fetal tissues, in particular the head where they will give rise to future brain microglia that are able to continuously self-renew throughout adulthood. EMPs seeding the fetal liver briefly expand to generate a local macrophage population, likely important for sustaining enucleation of primitive erythrocytes passing through the sinusoid prior to the establishment of definitive hematopoiesis and the generation of fetal monocyte-derived macrophages in the fetal liver.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585135&req=5

Figure 2: Primitive hematopoiesis and yolk sac macrophage ontogeny. Early EMPs emerge in the YS around E7.5 before establishment of the blood circulation. They express CD41 and CSF-1R and are independent of the transcription factor C-Myb. Upon establishment of the blood circulation around E8.5, EMPs differentiate into primitive macrophages as well as primitive erythrocytes and granulocytes. Primitive macrophages seed all fetal tissues, in particular the head where they will give rise to future brain microglia that are able to continuously self-renew throughout adulthood. EMPs seeding the fetal liver briefly expand to generate a local macrophage population, likely important for sustaining enucleation of primitive erythrocytes passing through the sinusoid prior to the establishment of definitive hematopoiesis and the generation of fetal monocyte-derived macrophages in the fetal liver.
Mentions: In mice, the first hematopoietic progenitors appear in the extra-embryonic YS blood islands at around embryonic age 7.25 (E7.25), where primitive hematopoiesis is initiated, producing mainly nucleated erythrocytes. This observation linked the myeloid progenitors observed in the YS at E7 with the emergence of YS macrophages after E9.0 [Figure 2; Ref. (42–45)]. Primitive hematopoiesis was also shown to produce megakaryocyte progenitors (46). The denomination “primitive” was given to reflect the production of embryonic erythroblasts, like those observed in lower species such as fish, amphibians, and birds, and remaining nucleated throughout their life span (47–49). This denomination was extended to macrophages in the YS due to their concomitant development prior to FL hematopoiesis. Interestingly, no clear evidence of monocytic intermediates was reported at this stage, although the seminal study of Cline and Moore did mention the existence of local intermediate cells between progenitors and functional macrophages (43). Studies by Naito and Takahashi et al. clarified the emergence of primitive macrophages in the YS blood islands in the mouse and rat, observing an absence of endogenous peroxidase activity as a surrogate marker for an absence of monocytic intermediates, such as those found in the BM (50–52), suggesting a unique developmental pathway for YS macrophages (53, 54).

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