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Journal ArticleDOI

Ontogeny of the haemopoietic system: yolk sac origin of in vivo and in vitro colony forming cells in the developing mouse embryo.

01 Mar 1970-British Journal of Haematology (Blackwell Publishing Ltd)-Vol. 18, Iss: 3, pp 279-296
TL;DR: The mouse yolk sac has been shown to contain in‐vivo colony forming cells capable of producing granulocytic, megakaryocytic and erythroid spleen colonies, and haemopoietic precursor cells demonstrated in the blood at the time of initiation of the circulation and in the early embryonic liver.
Abstract: Summary. The mouse yolk sac has been shown to contain in-vivo colony forming cells capable of producing granulocytic, megakaryocytic and erythroid spleen colonies; in-vitro colony forming cells producing granulocytic and mononuclear-macrophage colonies in agar; and cells capable of repopuiating the lymphoid and myeloid tissue of lethally irradiated hosts. Similar haemopoietic precursor cells were also demonstrated in the blood at the time of initiation of the circulation and in the early embryonic liver. Organ cultures of 7 day embryos with intact yolk sacs, and embryos or yolk sacs after separation have shown the autonomous nature of the development of haemopoiesis in the yolk sac and the dependence of intra-embryonic haemopoiesis, particularly in embryonic liver, on colonization by yolk sac haemopoietic cells. Both in-vivo and in-vitro colony forming cells have been involved in the first migration stream, between yolk sac and embryonic liver, and evidence has been presented for the role of local environmental factors in controlling the differentiation of these cell types. These results support the view that development of haemopoietic organs in both embryo and adult is dependent on colonization by circulating cells and that these circulating stem cells originate initially in the yolk sac. This indicates that the yolk sac is the only site of genuine de novo formation of haemopoietic stem cells.
Citations
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Journal ArticleDOI
22 Feb 2008-Cell
TL;DR: Studies of hematopoiesis provide critical insights of general relevance to other areas of stem cell biology including the role of cellular interactions in development and tissue homeostasis, lineage programming and reprogramming by transcription factors, and stage- and age-specific differences in cellular phenotypes.

2,266 citations


Cites background from "Ontogeny of the haemopoietic system..."

  • ...5 mouse embryos from which the yolk sac had been removed (Moore and Metcalf, 1970)....

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Journal ArticleDOI
07 Jan 2000-Cell
TL;DR: The review begins with a detailed examination of hematopoi-via the umbilical vein to the fetal liver between dpc 8.5 etic (blood-forming) stem cells, and the transcription pro-The earliest stem cells in ontogeny are totipotent, ex- files of each of these populations are quite distinct.

1,890 citations

Journal ArticleDOI
26 Feb 2015-Nature
TL;DR: It is shown in mice that the vast majority of adult tissue-resident macrophages originate from a Tie2+ (also known as Tek) cellular pathway generating Csf1r+ erythro-myeloid progenitors (EMPs) distinct from HSCs.
Abstract: Most haematopoietic cells renew from adult haematopoietic stem cells (HSCs), however, macrophages in adult tissues can self-maintain independently of HSCs. Progenitors with macrophage potential in vitro have been described in the yolk sac before emergence of HSCs, and fetal macrophages can develop independently of Myb, a transcription factor required for HSC, and can persist in adult tissues. Nevertheless, the origin of adult macrophages and the qualitative and quantitative contributions of HSC and putative non-HSC-derived progenitors are still unclear. Here we show in mice that the vast majority of adult tissue-resident macrophages in liver (Kupffer cells), brain (microglia), epidermis (Langerhans cells) and lung (alveolar macrophages) originate from a Tie2(+) (also known as Tek) cellular pathway generating Csf1r(+) erythro-myeloid progenitors (EMPs) distinct from HSCs. EMPs develop in the yolk sac at embryonic day (E) 8.5, migrate and colonize the nascent fetal liver before E10.5, and give rise to fetal erythrocytes, macrophages, granulocytes and monocytes until at least E16.5. Subsequently, HSC-derived cells replace erythrocytes, granulocytes and monocytes. Kupffer cells, microglia and Langerhans cells are only marginally replaced in one-year-old mice, whereas alveolar macrophages may be progressively replaced in ageing mice. Our fate-mapping experiments identify, in the fetal liver, a sequence of yolk sac EMP-derived and HSC-derived haematopoiesis, and identify yolk sac EMPs as a common origin for tissue macrophages.

1,626 citations

Journal ArticleDOI
20 Sep 1996-Cell
TL;DR: A novel in vitro organ culture system is presented demonstrating that, at day 10 in gestation, hematopoietic stem cells initiate autonomously and exclusively within the aorta-gonad-mesonephros (AGM) region, suggesting that the AGM region is the source of the definitive adult hematosynthesis system, which subsequently colonizes the liver.

1,498 citations


Cites background or methods from "Ontogeny of the haemopoietic system..."

  • ...Donor male cell contribugeous test system for identifying specific developmental tion was assessed semiquantitatively by PCR using YMT2/B primers hematopoietic defects in numerous recently reported and myogenin gene–specific oligonucleotides as the DNA normalhomologous recombination knockout mice (Pandolfi et ization control (Müller and Dzierzak, 1993)....

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  • ...We will continue to use the in fragments on a phosphorimager (Molecular Dynamics) and plottingvitro organ culture system for pre-LTR-HSC identificaagainst a graph derived from control samples of serial dilutions of tion within chimeric organs, for tracing the migration male DNA as described previously (Müller et al., 1994). and differentiation of LTR-HSCs, and for the study of the molecules involved in LTR-HSC initiation, expansion, Multilineage Analysis of Donor Cell Contribution and maturation....

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  • ...At 2 and 8 months about 2 embryo equivalents) when compared with the direct transplantation (3%; 3 positive out of 96 trans-posttransplantation, recipient peripheral blood DNAwas tested for the presence of the donor male marker....

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  • ...Hence, the At more than 6 months posttransplantation, recipients receiving 11 dpc cultured AGM region, YS, liver, and body remnant cells were analyzed for donor cell contribution by peripheral blood DNA PCR specific for YMT2/B and myogenin....

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  • ...(A) At 6 months posttransplantation, peripheral blood DNA samples were prepared as previously described, and donor male cell contribution was assessed semiquantitatively using myogenin gene–specific oligonucleotides as the DNA normalization control (Müller and Dzierzak, 1993; Medvinsky et al., 1993)....

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Journal ArticleDOI
15 Sep 1994-Nature
TL;DR: It is demonstrated that the transcription factor GATA-2 plays a critical role in haematopoiesis, particularly of an adult type, and proposed that it regulates genes controlling growth factor responsiveness or the proliferative capacity of early haem atopoietic cells.
Abstract: Blood cell development relies on the expansion and maintenance of haematopoietic stem and progenitor cells in the embryo. By gene targeting in mouse embryonic stem cells, we demonstrate that the transcription factor GATA-2 plays a critical role in haematopoiesis, particularly of an adult type. We propose that GATA-2 regulates genes controlling growth factor responsiveness or the proliferative capacity of early haematopoietic cells.

1,414 citations

References
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Journal ArticleDOI
TL;DR: Counts of macroscopic splenic colonies were used to obtain an estimate of the radiation sensitivity of normal mouse bone marrow progenitor cells.
Abstract: Counts of macroscopic splenic colonies were used to obtain an estimate of the radiation sensitivity of normal mouse bone marrow progenitor cells. Reproduced from Radiation Research 1961(Feb); 14(2): 213-222 by copyright permission of the Radiation Research Society (www.radres.org).

4,451 citations

Journal ArticleDOI
TL;DR: A simple in vitro technique for the growth of colonies from single cell suspensions of mouse bone marrow involves the plating of marrow cells in agar on feeder layers of other cells, those from 8-day-old mouse kidney and 17th day mouse embryo being shown to be the most efficient types of feeder layer.
Abstract: A simple in vitro technique is described for the growth of colonies from single cell suspensions of mouse bone marrow. The system involves the plating of marrow cells in agar on feeder layers of other cells, those from 8-day-old mouse kidney and 17th day mouse embryo being shown to be the most efficient types of feeder layers.

1,903 citations

Journal ArticleDOI
TL;DR: The spleen colony method is a quantitative method for the detection of progenitor cells that are capable of self-renewal and extensive proliferation in the spleens of irradiated mice as mentioned in this paper.
Abstract: Progenitor cells that are recognized by their ability to form colonies of descendants in the spleens of irradiated mice have the capacity for self-renewal. The distribution of new colony-forming cells per colony is extremely heterogeneous, indicating lax control of self-renewal. The capacities of colony-forming cells for self-renewal, for extensive proliferation, and for giving rise to differentiated descendants, fulfill three requirements for studies of stem cells. Thus, colony-forming cells may be considered to be class (though not necessarily the only class) of such progenitor cells, and the spleen colony method is a quantitative method for their detection. Journal of Cellular and Comparative Physiology copyright 1963 Wiley-Liss, Inc., A Wiley Company (www.interscience.Wiley.com).

922 citations