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Return to the hematopoietic stem cell origin.

Samokhvalov IM - Cell Regen (Lond) (2012)

Bottom Line: Studying embryonic hematopoiesis is complicated by diversity of its locations in the constantly changing anatomy and by the mobility of blood cell precursors.Non-invasive in vivo cell tracing methodology offers a better insight into complex processes of blood cell specification.Realistic knowledge of the blood origin is critical for safe and efficient recapitulation of hematopoietic development in culture.

View Article: PubMed Central - PubMed

Affiliation: South China Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530 China.

ABSTRACT
Studying embryonic hematopoiesis is complicated by diversity of its locations in the constantly changing anatomy and by the mobility of blood cell precursors. Embryonic hematopoietic progenitors are identified in traditional in vivo and in vitro cell potential assays. Profound epigenetic plasticity of mammalian embryonic cells combined with significant inductive capacity of the potential assays suggest that our understanding of hematopoietic ontogenesis is substantially distorted. Non-invasive in vivo cell tracing methodology offers a better insight into complex processes of blood cell specification. In contrast to the widely accepted view based on the cell potential assays, the genetic tracing approach identified the yolk sac as the source of adult hematopoietic stem cell lineage. Realistic knowledge of the blood origin is critical for safe and efficient recapitulation of hematopoietic development in culture.

No MeSH data available.


Yolk sac blood cells at E8.25-E8.5. Hematopoietic cells were visualized by Runx1/LacZ staining. (a) “Blood island” - like cell aggregations appear in the proximal yolk sac at around the start of blood circulation. The red arrow points to blood cells on their way through vitelline vein into embryonic vasculature. (b) Dense cell clusters in the proximal region of the yolk sac resist the circulation drive for some period of time. (c) In pre-circulation conceptus blood cells start to move distally before the yolk sac vascular plexus fuses with the embryo vasculature.
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Fig1: Yolk sac blood cells at E8.25-E8.5. Hematopoietic cells were visualized by Runx1/LacZ staining. (a) “Blood island” - like cell aggregations appear in the proximal yolk sac at around the start of blood circulation. The red arrow points to blood cells on their way through vitelline vein into embryonic vasculature. (b) Dense cell clusters in the proximal region of the yolk sac resist the circulation drive for some period of time. (c) In pre-circulation conceptus blood cells start to move distally before the yolk sac vascular plexus fuses with the embryo vasculature.

Mentions: During gastrulation the extraembryonic mesoderm moves towards the ectoplacental cone and builds up significant cell masses in the proximal yolk sac region at around E7.5. These mesodermal cell masses accumulate globin during the day 9 of gestation (E8.0-E9.0) and develop into structures which are called the “blood islands” which look like reddish spots in the proximal part of dissected yolk sac. It has long been thought that inner cells of the islands become blood cells, whereas the external ones develop into endothelium [69]. This, however, may not be the case. Detailed fluorescent immunohistochemical analysis of the early yolk sac revealed quite a different picture of extraembryonic mesoderm specification [70]. The proximal mesodermal cell masses turned out to specialize almost exclusively into blood cells. Apparently, the proximal yolk sac is the first anatomical site of active de novo hematopoiesis in the conceptus. Emerging more distally vascular plexus was found to expand proximally and envelop emerging blood cells squeezing them inside of the newly formed vessels. Massive red spots of blood islands probably correspond to big cell aggregations that become later vascularized and release blood cells into developing vascular plexus (Figure 1a). Some cell clusters still look quite dense even when yolk sac becomes well vascularized (Figure 1b). These transient aggregations may give rise to Runx1high clusters of definitive precursor cells, which presumably contain members of the HSC lineage [6]. A great majority of cells arising from the proximal mesodermal masses are primitive erythroblasts, and they start to spread distally before blood circulation is initiated (Figure 1c). These cells might be pushed by the large number of blood island cells which become non-adherent at E8.0-E8.5. Circulation significantly increases the spreading, but for some period of time most of red blood cells are still retained within the yolk sac [71], which suggests that development of vasculature in the yolk sac substantially outpaces it in the embryo proper. Importantly, the cells with the definitive progenitor potential have significantly higher affinity to the yolk sac microenvironment at E9.5-E10.5 suggesting that the yolk sac works as temporary pre-liver niche for immature blood cells precursors [71]. Some of those precursors can be visualized by staining with CD41, and clusters of CD41bright cells can be seen at the early somite stage within blood island [70]. It is possible that the CD41bright clusters correspond to the Runx1high cell aggregates detected at the same stage and in the same region by LacZ staining [6].Figure 1


Return to the hematopoietic stem cell origin.

Samokhvalov IM - Cell Regen (Lond) (2012)

Yolk sac blood cells at E8.25-E8.5. Hematopoietic cells were visualized by Runx1/LacZ staining. (a) “Blood island” - like cell aggregations appear in the proximal yolk sac at around the start of blood circulation. The red arrow points to blood cells on their way through vitelline vein into embryonic vasculature. (b) Dense cell clusters in the proximal region of the yolk sac resist the circulation drive for some period of time. (c) In pre-circulation conceptus blood cells start to move distally before the yolk sac vascular plexus fuses with the embryo vasculature.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230910&req=5

Fig1: Yolk sac blood cells at E8.25-E8.5. Hematopoietic cells were visualized by Runx1/LacZ staining. (a) “Blood island” - like cell aggregations appear in the proximal yolk sac at around the start of blood circulation. The red arrow points to blood cells on their way through vitelline vein into embryonic vasculature. (b) Dense cell clusters in the proximal region of the yolk sac resist the circulation drive for some period of time. (c) In pre-circulation conceptus blood cells start to move distally before the yolk sac vascular plexus fuses with the embryo vasculature.
Mentions: During gastrulation the extraembryonic mesoderm moves towards the ectoplacental cone and builds up significant cell masses in the proximal yolk sac region at around E7.5. These mesodermal cell masses accumulate globin during the day 9 of gestation (E8.0-E9.0) and develop into structures which are called the “blood islands” which look like reddish spots in the proximal part of dissected yolk sac. It has long been thought that inner cells of the islands become blood cells, whereas the external ones develop into endothelium [69]. This, however, may not be the case. Detailed fluorescent immunohistochemical analysis of the early yolk sac revealed quite a different picture of extraembryonic mesoderm specification [70]. The proximal mesodermal cell masses turned out to specialize almost exclusively into blood cells. Apparently, the proximal yolk sac is the first anatomical site of active de novo hematopoiesis in the conceptus. Emerging more distally vascular plexus was found to expand proximally and envelop emerging blood cells squeezing them inside of the newly formed vessels. Massive red spots of blood islands probably correspond to big cell aggregations that become later vascularized and release blood cells into developing vascular plexus (Figure 1a). Some cell clusters still look quite dense even when yolk sac becomes well vascularized (Figure 1b). These transient aggregations may give rise to Runx1high clusters of definitive precursor cells, which presumably contain members of the HSC lineage [6]. A great majority of cells arising from the proximal mesodermal masses are primitive erythroblasts, and they start to spread distally before blood circulation is initiated (Figure 1c). These cells might be pushed by the large number of blood island cells which become non-adherent at E8.0-E8.5. Circulation significantly increases the spreading, but for some period of time most of red blood cells are still retained within the yolk sac [71], which suggests that development of vasculature in the yolk sac substantially outpaces it in the embryo proper. Importantly, the cells with the definitive progenitor potential have significantly higher affinity to the yolk sac microenvironment at E9.5-E10.5 suggesting that the yolk sac works as temporary pre-liver niche for immature blood cells precursors [71]. Some of those precursors can be visualized by staining with CD41, and clusters of CD41bright cells can be seen at the early somite stage within blood island [70]. It is possible that the CD41bright clusters correspond to the Runx1high cell aggregates detected at the same stage and in the same region by LacZ staining [6].Figure 1

Bottom Line: Studying embryonic hematopoiesis is complicated by diversity of its locations in the constantly changing anatomy and by the mobility of blood cell precursors.Non-invasive in vivo cell tracing methodology offers a better insight into complex processes of blood cell specification.Realistic knowledge of the blood origin is critical for safe and efficient recapitulation of hematopoietic development in culture.

View Article: PubMed Central - PubMed

Affiliation: South China Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530 China.

ABSTRACT
Studying embryonic hematopoiesis is complicated by diversity of its locations in the constantly changing anatomy and by the mobility of blood cell precursors. Embryonic hematopoietic progenitors are identified in traditional in vivo and in vitro cell potential assays. Profound epigenetic plasticity of mammalian embryonic cells combined with significant inductive capacity of the potential assays suggest that our understanding of hematopoietic ontogenesis is substantially distorted. Non-invasive in vivo cell tracing methodology offers a better insight into complex processes of blood cell specification. In contrast to the widely accepted view based on the cell potential assays, the genetic tracing approach identified the yolk sac as the source of adult hematopoietic stem cell lineage. Realistic knowledge of the blood origin is critical for safe and efficient recapitulation of hematopoietic development in culture.

No MeSH data available.