Human hematopoietic stem cell engraftment in goat
Ontology highlight
ABSTRACT:
ORGANISM(S): Capra hircus Homo sapiens
PROVIDER: GSE1801 | GEO | 2004/10/14
SECONDARY ACCESSION(S): PRJNA90277
REPOSITORIES: GEO
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Project description:Robust human-goat chimerism was achieved by transplanting human CD34+Lin- cord blood cells into fetal goats. We observed a broad distribution of GFP-marked human cells in non-hematopoietic organs including kidney, muscle, lung, and heart of transplant goats. Various marker techniques indicated that human genes were expressed in chimeric livers and blood.
2007-07-19 | E-GEOD-1801 | biostudies-arrayexpress
Project description:To evaluate the long-term growth potential of BCR-ABL-transduced primitive human hematopoietic cells, lin- cord blood cells containing an MSCV-BCR-ABL-IRES-GFP (BCR-ABL) or control-GFP transgene (MIG) were injected IP into fetal goats at 45-55 days of gestation. Six transplant goats were born alive. One was examined three weeks after birth and showed GFP+ cells in the blood, bone marrow (BM), liver, kidney, lung, heart, and both skeletal and smooth muscle. FISH analysis also showed the liver of this goat contained BCR-ABL-GFP transgenic cells. The remaining five goats appear normal although, in some, the WBC count is elevated 3- to 5-fold. GFP+ cells, including cells identifiable by FACS as human CD34+ cells, have been detected in the blood of all these goats. The presence of BCR-ABL-GFP transgenic cells in the BM and liver was confirmed by FISH analysis, and quantitative real-time PCR analysis of genomic DNA isolated from unpurified BM cells obtained from three of the transplant goats demonstrated 3-5Ã104 copies of the transgene per microgram of DNA. Microarray transcript profiling was performed on blood and liver tissues of normal goats, BCR-ABL chimeric goats, MIG chimeric goats, and normal human samples. RNA for human genes was detected in goats transplanted with cord blood cells but not in normal goats, and the RNA abundance of some genes in BCR-ABL chimeric goat blood was similar to or greater than levels observed in MIG goat blood or normal human samples. Quantitative RT-PCR confirmed the differential expression of several genes in goats carrying the BCR-ABL vs. control transgene. These results demonstrate long-term engraftment but slow expansion in a large animal model of primitive human hematopoietic cells transduced with a BCR-ABL fusion gene and transplanted in utero. This novel xenotransplant goat model should be useful for analyzing the initial phases of development of human CML and for assessing new therapies with potential long-term benefits. Experiment Overall Design: Total RNA was extracted from liver (L) and blood (B) samples of normal goats (ng), humans (hu), chimeric goats engrafted with human cord blood stem cells containing control (mig) vector, and chimeric goats engrafted with CML (bcrabl) vector. RNA samples were profiled on Affymetrix human U133A GeneChips and examined for differentially expressed genes in CML vs control goats, filtering for signals significantly above background levels observed in normal goat to select for specific human gene expression.
2009-08-23 | E-GEOD-17588 | biostudies-arrayexpress
Project description:To evaluate the long-term growth potential of BCR-ABL-transduced primitive human hematopoietic cells, lin- cord blood cells containing an MSCV-BCR-ABL-IRES-GFP (BCR-ABL) or control-GFP transgene (MIG) were injected IP into fetal goats at 45-55 days of gestation. Six transplant goats were born alive. One was examined three weeks after birth and showed GFP+ cells in the blood, bone marrow (BM), liver, kidney, lung, heart, and both skeletal and smooth muscle. FISH analysis also showed the liver of this goat contained BCR-ABL-GFP transgenic cells. The remaining five goats appear normal although, in some, the WBC count is elevated 3- to 5-fold. GFP+ cells, including cells identifiable by FACS as human CD34+ cells, have been detected in the blood of all these goats. The presence of BCR-ABL-GFP transgenic cells in the BM and liver was confirmed by FISH analysis, and quantitative real-time PCR analysis of genomic DNA isolated from unpurified BM cells obtained from three of the transplant goats demonstrated 3-5×104 copies of the transgene per microgram of DNA. Microarray transcript profiling was performed on blood and liver tissues of normal goats, BCR-ABL chimeric goats, MIG chimeric goats, and normal human samples. RNA for human genes was detected in goats transplanted with cord blood cells but not in normal goats, and the RNA abundance of some genes in BCR-ABL chimeric goat blood was similar to or greater than levels observed in MIG goat blood or normal human samples. Quantitative RT-PCR confirmed the differential expression of several genes in goats carrying the BCR-ABL vs. control transgene. These results demonstrate long-term engraftment but slow expansion in a large animal model of primitive human hematopoietic cells transduced with a BCR-ABL fusion gene and transplanted in utero. This novel xenotransplant goat model should be useful for analyzing the initial phases of development of human CML and for assessing new therapies with potential long-term benefits.
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Project description:The aim of the study was to investigate differences in the gene expression profiles of selected tissues in two most popular goat’s breeds in Poland: Polish White Improved (PWI) and Polish Fawn Improved (PFI). Three different types of tissue samples were selected: somatic cells isolated from goats’ milk (MSC), milk fat globules (MFG) and peripheral nuclear blood cells (PBNC) Since there were no earlier genetic studies focused on genetic differences between these two goat breeds we decided to evaluate hypothetical genomic differences assuming that such a differences should be the consequence of genetic differences. We created the hypothesis that if genomic differences exist they should be revealed in hierarchical clustering of transcriptomic profiles of selected tissues. Should the genomic differences exist the clusters obtained are grouping goat breeds and not goat’s tissues. The results of hierarchical clustering however show something completely different. The clusters are grouping goat tissues (milk fat globules, milk somatic cells, peripheral blood nuclear cells) without any relation with goat breed. So the analytical tool does not recognize the goat breed as a driver of transcriptomic difference. Moreover, we were not able to find significantly regulated genes between two breeds
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Project description:We have used RNA-Seq to examine long non-coding RNAs (lncRNAs) and mRNAs from PPRV infected goat tissues (Lung, Spleen and Caecum). Our study reveals the prevalence of lncRNAs in goats, and has identified lncRNAs differentially expressed in different tissues of PPRV (Izatnagar94) infected goats, suggesting its important functions during virus infection.
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Project description:Human hematopoietic stem cell engraftment in goat
| PRJNA90277 | ENA
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