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Robert Auerbach - One of the best experts on this subject based on the ideXlab platform.
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in vitro and in vivo differentiation into b cells t cells and myeloid cells of primitive Yolk Sac hematopoietic precursor cells expanded 100 fold by coculture with a clonal Yolk Sac endothelial cell line
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Shur Jen Wang, Robert AuerbachAbstract:The Yolk Sac, first site of hematopoiesis during mammalian development, contains not only hematopoietic stem cells but also the earliest precursors of endothelial cells. We have previously shown that a nonadherent Yolk Sac cell population (WGA+, density 100 fold within 8 days by coculture with irradiated C166 cells. Colony-forming ability was retained for at least three passages in vitro, with retention of the ability to differentiate into T-cell, B-cell, and myeloid lineages. Stem cell properties were maintained by a significant fraction of nonadherent cells in the third passage, although these stem cells expressed a somewhat more mature cell surface phenotype than the initial Yolk Sac stem cells. When reintroduced into adult allogeneic immunocompromised (scid) hosts, they were able to give rise to all of the leukocyte lineages, including T cells, B cells, and myeloid cells. We conclude that Yolk Sac endothelial cells can support the stable proliferation of multipotential hematopoietic stem cells, thus generating adequate numbers of cells for study of the mechanisms involved in their subsequent development and differentiation, for in vivo hematopoietic restitution, and for potential use as a vehicle for gene transfer.
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in vitro differentiation of b cells and myeloid cells from the early mouse embryo and its extraembryonic Yolk Sac
Experimental Hematology, 1994Co-Authors: Hua Huang, L D Zettergren, Robert AuerbachAbstract:The Yolk Sac is the first site of hematopoiesis during ontogeny. However, the source of early embryonic hematopoietic stem cells remains unresolved. Early studies have shown that cells obtained from day-8 and -9 extraembryonic Yolk Sacs can give rise to T cells and myeloid cells, whereas the embryo itself appears to lack such cells. Controversy remains as to whether it is the embryo itself or the extraembryonic Yolk Sac that contains the initial precursors capable of differentiating into B cells. This study used the approach of enriching hematopoietic stem cells by immunocytoadherence and studying cells isolated from within the embryo itself or from the Yolk Sac obtained at days 8 and 9 of mouse embryonic development. We report that on day 9, both Yolk Sac-derived and embryo-derived cells can give rise to B cells and myeloid cells in vitro. On day 8, however, cells isolated from the Yolk Sac but not from the embryo produce myeloid colonies in vitro; neither source of stem cells generates B cells. Our study suggests that myeloid precursors migrate from Yolk Sac to embryo earlier than has previously been reported but that the origin for B cell precursors remains to be determined.
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identification and characterization of hematopoietic stem cells from the Yolk Sac of the early mouse embryo
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Hua Huang, Robert AuerbachAbstract:Abstract The Yolk Sac is the first site of hematopoiesis in the mammalian embryo. However, little is known about the initial stem cells in the Yolk Sac. We have isolated hematopoietic stem cells from early mouse embryonic Yolk Sac by using a sequential protocol of nonadherence to plastic, density gradient centrifugation, immunocytoadherence, and cell sorting. Isolated, nonadherent, density < 1.077-g/cm3, surface antigen AA4.1+, wheat germ agglutinin bright (WGAbright) cells give rise to multiple lineages, including T cells, B cells, and myeloid cells, as detected by using fetal thymus organ culture, S17 stromal feeder layers, or methylcellulose culture colony-forming cells, respectively. AA4.1+, WGAbright cells expressed high levels of heat-stable antigen (HSA) and CD45 (Ly-5) but did not significantly express major histocompatibility complex antigens, CD44, or Sca-1. Peak stem cell concentration is reached by day 11, before stem cells can be found in the liver, omentum, or thymus. In vivo long-term reconstitution of lethally irradiated mice was effected by as few as 720 AA4.1+, WGAbright Yolk Sac cells, but it required addition of a subset of bone marrow cells capable of providing immediate (short-term) radiation protection. Yolk Sac donor-derived T cells, B cells, and macrophages were readily identified 6 months after transfer of Yolk Sac-derived stem cells. We suggest that, because of their cell surface phenotype as well as their capacity to differentiate in vitro and in vivo, the cells isolated from the mouse embryonic Yolk Sac may include the most primitive hematopoietic pluripotential stem cells yet identified.
Ff Bruveris - One of the best experts on this subject based on the ideXlab platform.
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human Yolk Sac like haematopoiesis generates runx1 gfi1 and or gfi1b dependent blood and sox17 positive endothelium
Development, 2020Co-Authors: Ff Bruveris, Ar Leitoguinho, Ali Motazedian, Katerina Vlahos, Koula Sourris, Robyn Mayberry, Penelope McdonaldAbstract:The genetic regulatory network controlling early fate choices during human blood cell development are not well understood. We used human pluripotent stem cell reporter lines to track the development of endothelial and haematopoietic populations in an in vitro model of human Yolk-Sac development. We identified SOX17-CD34+CD43- endothelial cells at day 2 of blast colony development, as a haemangioblast-like branch point from which SOX17-CD34+CD43+ blood cells and SOX17+CD34+CD43- endothelium subsequently arose. Most human blood cell development was dependent on RUNX1. Deletion of RUNX1 only permitted a single wave of Yolk Sac-like primitive erythropoiesis, but no Yolk Sac myelopoiesis or aorta-gonad-mesonephros (AGM)-like haematopoiesis. Blocking GFI1/1B activity with a small molecule inhibitor abrogated all blood cell development, even in cell lines with an intact RUNX1 gene. Together, our data defines the hierarchical requirements for both RUNX1 and GFI1/1B during early human haematopoiesis arising from a Yolk Sac-like SOX17-negative haemogenic endothelial intermediate.
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Human Yolk Sac-like haematopoiesis generates RUNX1-, GFI1- and/or GFI1B-dependent blood and SOX17-positive endothelium
'The Company of Biologists', 2020Co-Authors: Ff Bruveris, Ar Leitoguinho, Motazedian A, Vlahos K, Sourris K, Mayberry R, Mcdonald P, Azzola L, Nm DavidsonAbstract:The genetic regulatory network controlling early fate choices during human blood cell development are not well understood. We used human pluripotent stem cell reporter lines to track the development of endothelial and haematopoietic populations in an in vitro model of human Yolk-Sac development. We identified SOX17-CD34+CD43- endothelial cells at day 2 of blast colony development, as a haemangioblast-like branch point from which SOX17-CD34+CD43+ blood cells and SOX17+CD34+CD43- endothelium subsequently arose. Most human blood cell development was dependent on RUNX1. Deletion of RUNX1 only permitted a single wave of Yolk Sac-like primitive erythropoiesis, but no Yolk Sac myelopoiesis or aorta-gonad-mesonephros (AGM)-like haematopoiesis. Blocking GFI1 and/or GFI1B activity with a small molecule inhibitor abrogated all blood cell development, even in cell lines with an intact RUNX1 gene. Together, our data define the hierarchical requirements for RUNX1, GFI1 and/or GFI1B during early human haematopoiesis arising from a Yolk Sac-like SOX17-negative haemogenic endothelial intermediate
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human Yolk Sac like haematopoiesis generates runx1 and gfi1 1b dependent blood and sox17 positive endothelium
Development, 2020Co-Authors: Ff Bruveris, Ar Leitoguinho, Ali Motazedian, Katerina Vlahos, Koula Sourris, Robyn Mayberry, Penelope McdonaldAbstract:The genetic regulatory network controlling early fate choices during human blood cell development are not well understood. We used human pluripotent stem cell reporter lines to track the development of endothelial and haematopoietic populations in an in vitro model of human Yolk-Sac development. We identified SOX17-CD34+CD43- endothelial cells at day 2 of blast colony development, as a haemangioblast-like branch point from which SOX17-CD34+CD43+ blood cells and SOX17+CD34+CD43- endothelium subsequently arose. Most human blood cell development was dependent on RUNX1. Deletion of RUNX1 only permitted a single wave of Yolk Sac-like primitive erythropoiesis, but no Yolk Sac myelopoiesis or aorta-gonad-mesonephros (AGM)-like haematopoiesis. Blocking GFI1/1B activity with a small molecule inhibitor abrogated all blood cell development, even in cell lines with an intact RUNX1 gene. Together, our data defines the hierarchical requirements for both RUNX1 and GFI1/1B during early human haematopoiesis arising from a Yolk Sac-like SOX17-negative haemogenic endothelial intermediate.
Hua Huang - One of the best experts on this subject based on the ideXlab platform.
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in vitro differentiation of b cells and myeloid cells from the early mouse embryo and its extraembryonic Yolk Sac
Experimental Hematology, 1994Co-Authors: Hua Huang, L D Zettergren, Robert AuerbachAbstract:The Yolk Sac is the first site of hematopoiesis during ontogeny. However, the source of early embryonic hematopoietic stem cells remains unresolved. Early studies have shown that cells obtained from day-8 and -9 extraembryonic Yolk Sacs can give rise to T cells and myeloid cells, whereas the embryo itself appears to lack such cells. Controversy remains as to whether it is the embryo itself or the extraembryonic Yolk Sac that contains the initial precursors capable of differentiating into B cells. This study used the approach of enriching hematopoietic stem cells by immunocytoadherence and studying cells isolated from within the embryo itself or from the Yolk Sac obtained at days 8 and 9 of mouse embryonic development. We report that on day 9, both Yolk Sac-derived and embryo-derived cells can give rise to B cells and myeloid cells in vitro. On day 8, however, cells isolated from the Yolk Sac but not from the embryo produce myeloid colonies in vitro; neither source of stem cells generates B cells. Our study suggests that myeloid precursors migrate from Yolk Sac to embryo earlier than has previously been reported but that the origin for B cell precursors remains to be determined.
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identification and characterization of hematopoietic stem cells from the Yolk Sac of the early mouse embryo
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Hua Huang, Robert AuerbachAbstract:Abstract The Yolk Sac is the first site of hematopoiesis in the mammalian embryo. However, little is known about the initial stem cells in the Yolk Sac. We have isolated hematopoietic stem cells from early mouse embryonic Yolk Sac by using a sequential protocol of nonadherence to plastic, density gradient centrifugation, immunocytoadherence, and cell sorting. Isolated, nonadherent, density < 1.077-g/cm3, surface antigen AA4.1+, wheat germ agglutinin bright (WGAbright) cells give rise to multiple lineages, including T cells, B cells, and myeloid cells, as detected by using fetal thymus organ culture, S17 stromal feeder layers, or methylcellulose culture colony-forming cells, respectively. AA4.1+, WGAbright cells expressed high levels of heat-stable antigen (HSA) and CD45 (Ly-5) but did not significantly express major histocompatibility complex antigens, CD44, or Sca-1. Peak stem cell concentration is reached by day 11, before stem cells can be found in the liver, omentum, or thymus. In vivo long-term reconstitution of lethally irradiated mice was effected by as few as 720 AA4.1+, WGAbright Yolk Sac cells, but it required addition of a subset of bone marrow cells capable of providing immediate (short-term) radiation protection. Yolk Sac donor-derived T cells, B cells, and macrophages were readily identified 6 months after transfer of Yolk Sac-derived stem cells. We suggest that, because of their cell surface phenotype as well as their capacity to differentiate in vitro and in vivo, the cells isolated from the mouse embryonic Yolk Sac may include the most primitive hematopoietic pluripotential stem cells yet identified.
Stephen G Matthews - One of the best experts on this subject based on the ideXlab platform.
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breast cancer resistance protein bcrp abcg2 is selectively modulated by lipopolySaccharide lps in the mouse Yolk Sac
Reproductive Toxicology, 2020Co-Authors: Lilian M Martinelli, Mila W Reginatto, Klaus N Fontes, Cherley Borba Vieira De Andrade, Victoria R S Monteiro, Hanailly Ribeiro Gomes, F R C L Almeida, Flavia Fonseca Bloise, Stephen G Matthews, Tânia M OrtigacarvalhoAbstract:Bacterial infection alters placental ABC transporters expression. These transporters provide fetal protection against circulating xenobiotics and environmental toxins present in maternal blood. We hypothesized that lipopolySaccharide (LPS-bacterial mimic) alters the Yolk Sac morphology and expression of key ABC transporters in a gestational-age dependent manner. Yolk Sac samples from C57BL/6 mice were obtained at gestational ages (GD) 15.5 and GD18.5, 4 or 24 hours after LPS exposure (150ug/kg; n = 8/group). Samples underwent morphometrical, qPCR and immunohistochemistry analysis. The volumetric proportions of the histological components of the Yolk Sac did not change in response to LPS. LPS increased Abcg2 expression at GD15.5, after 4 h of treatment (p < 0.05). No changes in Abca1, Abcb1a/b, Abcg1, Glut1, Snat1, Il-1β, Ccl2 and Mif were observed. Il-6 and Cxcl1 were undetectable in the Yolk Sac throughout pregnancy. Abca1, breast cancer resistance protein (Bcrp, encoded by Abcg2) and P-glycoprotein (P-gp/ Abcb1a/b) were localized in the endodermal (uterine-facing) epithelium and to a lesser extent in the mesothelium (amnion-facing), whereas Abca1 was also localized to the endothelium of the Yolk Sac blood vessels. LPS increased the labeling area and intensity of Bcrp in the Yolk Sac's mesothelial cells at GD15.5 (4 h), whereas at GD18.5, the area of Bcrp labeling in the mesothelium (4 and 24 h) was decreased (p < 0.05). Bacterial infection has the potential to change Yolk Sac barrier function by affecting Bcrp and Abcg2 expression in a gestational-age dependent-manner. These changes may alter fetal exposure to xenobiotics and toxic substances present in the maternal circulation and in the uterine cavity.
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breast cancer resistance protein bcrp1 abcg2 in mouse placenta and Yolk Sac ontogeny and its regulation by progesterone
Placenta, 2007Co-Authors: Grazyna M Kalabis, Sophie Petropoulos, W Gibb, Stephen G MatthewsAbstract:Breast Cancer Resistance Protein (BCRP), a recently-discovered transporter belonging to ABC superfamily, is highly expressed within the labyrinth of the placenta, the primary site of exchange between the maternal and fetal circulation. It has been proposed to function as an efflux pump protecting the fetus from a wide range of xenobiotics. It has also been recently shown that the Yolk Sac, in addition to the placenta, may be involved in transport of certain substances to and from the fetus. We hypothesised that there are changes in placental Bcrp1 (the mouse orthologue of human BCRP) expression during pregnancy and that these correlate with changes in progesterone production that occur in late gestation. We also hypothesised that Bcrp1 is expressed in the Yolk Sac, and that levels change with advancing gestation. Either whole concepti, or placenta and Yolk Sac, were collected from pregnant mice and analysed at embryonic (E) day 9.5, 12.5, 15.5 and 18.5 (term approximately E19.5). Peak expression of Bcrp1 mRNA was detected using in situ hybridisation within the placenta at E9.5 and the Yolk Sac at E12.5. There was a significant decrease thereafter in both tissues (p<0.001). In contrast, expression of Bcrp1 protein as assessed by immunohistochemistry and Western immunoblots did not change significantly during gestation either in the placenta nor the Yolk Sac, and no sex difference in Bcrp1 protein expression in either tissue was observed at E12.5. Daily progesterone treatment starting at E14.5 and continuing until E18.5 significantly increased maternal progesterone levels, but did not elicit any changes in the Bcrp1 mRNA or Bcrp1 protein expression either in the placenta or the Yolk Sac. Significant expression of Bcrp1 protein in fetal tissue was evident at the end of gestation, while expression in the fetal brain endothelium was evident as early as E12.5. We suggest that the placenta and the Yolk Sac, both of which express Bcrp1, may limit fetal exposure to the potentially adverse effects of xenobiotics including therapeutic drugs which the mother may be exposed to during pregnancy. The significant decrease in Bcrp1 mRNA expression in both the Yolk Sac and the placenta from mid to late gestation may be counter-balanced by an increase in Bcrp1 expression in fetal organs involved in absorption, excretion and protection.
Penelope Mcdonald - One of the best experts on this subject based on the ideXlab platform.
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human Yolk Sac like haematopoiesis generates runx1 gfi1 and or gfi1b dependent blood and sox17 positive endothelium
Development, 2020Co-Authors: Ff Bruveris, Ar Leitoguinho, Ali Motazedian, Katerina Vlahos, Koula Sourris, Robyn Mayberry, Penelope McdonaldAbstract:The genetic regulatory network controlling early fate choices during human blood cell development are not well understood. We used human pluripotent stem cell reporter lines to track the development of endothelial and haematopoietic populations in an in vitro model of human Yolk-Sac development. We identified SOX17-CD34+CD43- endothelial cells at day 2 of blast colony development, as a haemangioblast-like branch point from which SOX17-CD34+CD43+ blood cells and SOX17+CD34+CD43- endothelium subsequently arose. Most human blood cell development was dependent on RUNX1. Deletion of RUNX1 only permitted a single wave of Yolk Sac-like primitive erythropoiesis, but no Yolk Sac myelopoiesis or aorta-gonad-mesonephros (AGM)-like haematopoiesis. Blocking GFI1/1B activity with a small molecule inhibitor abrogated all blood cell development, even in cell lines with an intact RUNX1 gene. Together, our data defines the hierarchical requirements for both RUNX1 and GFI1/1B during early human haematopoiesis arising from a Yolk Sac-like SOX17-negative haemogenic endothelial intermediate.
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human Yolk Sac like haematopoiesis generates runx1 and gfi1 1b dependent blood and sox17 positive endothelium
Development, 2020Co-Authors: Ff Bruveris, Ar Leitoguinho, Ali Motazedian, Katerina Vlahos, Koula Sourris, Robyn Mayberry, Penelope McdonaldAbstract:The genetic regulatory network controlling early fate choices during human blood cell development are not well understood. We used human pluripotent stem cell reporter lines to track the development of endothelial and haematopoietic populations in an in vitro model of human Yolk-Sac development. We identified SOX17-CD34+CD43- endothelial cells at day 2 of blast colony development, as a haemangioblast-like branch point from which SOX17-CD34+CD43+ blood cells and SOX17+CD34+CD43- endothelium subsequently arose. Most human blood cell development was dependent on RUNX1. Deletion of RUNX1 only permitted a single wave of Yolk Sac-like primitive erythropoiesis, but no Yolk Sac myelopoiesis or aorta-gonad-mesonephros (AGM)-like haematopoiesis. Blocking GFI1/1B activity with a small molecule inhibitor abrogated all blood cell development, even in cell lines with an intact RUNX1 gene. Together, our data defines the hierarchical requirements for both RUNX1 and GFI1/1B during early human haematopoiesis arising from a Yolk Sac-like SOX17-negative haemogenic endothelial intermediate.
