mortality/aging
• acute lethality by E18.5
• no gross defects detected from E14.5-E16.5
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hematopoietic system
• HSCs from E14.5 mice are less than doubled in number after 7 days in culture compared to over 1000-fold increase for wild-type cells
• HSCs from E17.5 mice in culture for 7 days fail to produce any viable cells
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• fetal liver cellularity is significantly decreased from E14.5 to E17.5
• at E16.5 and E17.5 there are significantly fewer fetal liver CD45+ leukocytes
• by E17.5, both lymphoid and myeloid lineages are dramatically depleted
• decrease in the number of lymphoid-primed multipotent progenitors and myeloerythroid progenitors at E16.5 and E17.5 in the fetal liver
• unlike in controls, no increase in hematopoietic progenitor cells between E16.5 and E17.5
• near complete failure of establishment of bone marrow hematopoiesis
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• at E16.5 and E17.5 in the fetal liver
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• by E17.5, both lymphoid and myeloid lineages are dramatically depleted
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• by E17.5, both lymphoid and myeloid lineages are dramatically depleted
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• near-complete failure to establish hematopoiesis in the bone marrow
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• at E16.5 and E17.5 in the fetal liver
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• at E16.5 and E17.5 in the fetal liver
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• absence of LSK cells in the bone marrow at E16.5-E17.5 accompanied by few, if any, bone marrow located committed progenitors and significantly fewer mature lineage progenitors
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• more than double the number of LSK multipotent progenitors at E14.5, however, this difference levels off between E16.5 and E17.5
• there are also more HSCs at E14.5 and this difference is sustained through E17.5
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• RNAseq analysis indicates HSCs lack the erythroid primed subpopulation
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cellular
• at E17.5 a greater proportion of fetal liver LSK multipotent progenitors accumulate in G1
• significant increase in the proportion of granulocyte lineage cells in G0 and decrease in the proportion in S/M phase
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• in a transplantation assay HSCs fail to home to either the bone marrow, spleen, or liver
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• HSCs from E14.5 mice are less than doubled in number after 7 days in culture compared to over 1000-fold increase for wild-type cells
• HSCs from E17.5 mice in culture for 7 days fail to produce any viable cells
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liver/biliary system
• fetal liver cellularity is significantly decreased from E14.5 to E17.5
• at E16.5 and E17.5 there are significantly fewer fetal liver CD45+ leukocytes
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growth/size/body
• significant growth retardation at E17.5 and E18.5 but not from E14.5 to E16.5
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immune system
• by E17.5, both lymphoid and myeloid lineages are dramatically depleted
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• by E17.5, both lymphoid and myeloid lineages are dramatically depleted
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