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Transplanting FVIII/ET3-Secreting Cells in Fetal Sheep Increases FVIII Levels Long-Term Without Inducing Immunity or Toxicity

ABSTRACT: To investigate the differentiative fate of human PLCs following transplantation into fetal sheep and engraftment in various tissues/organs, we performed gene expression profiling analysis using data obtained from RNA-seq of human PLCs prior to in utero transplantation and of each engrafted fetal sheep tissue after filtering to remove any cross-reactivity with orthologous sheep transcripts

ORGANISM(S): Homo sapiens Ovis aries

PROVIDER: GSE230081 | GEO | 2023/06/01

REPOSITORIES: GEO

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Project description:Expression data from Sheep longissimus dorsi (LD) muscle during development; fetal lambs (80, 100, 120 days gestation), new born lambs at birth (150 d) and lambs at 12 weeks (230 d) The fetal to neonatal developmental transition corresponds with profound changes in skeletal muscle function as it adapts to the new physiological demands of locomotion and postural support against gravity. The mechanisms underpinning this adaption process are unclear but are likely to be initiated by changes in hormone levels occurring during the major developmental transition. We tested the hypothesis that this period is associated with changes in the transcription of skeletal muscle genes, particularly genes involved in oxidative metabolism. Using an ovine model, transcriptional profiling was performed on longissimus dorsi skeletal muscle taken at three fetal developmental time points (80, 100 and 120 d of fetal development) as well as two postnatal time points, one within 3 days after birth and a second at 12 weeks of age. The developmental time course was dominated by large changes in the expression of 2471 genes during the period from late fetal development (120 d fetal development) to birth (within 1-3 days of birth). Analysis of the functions of the genes that were uniquely up-regulated in this period showed strong enrichment for oxidative metabolism and the TCA cycle indicating enhanced mitochondrial activity. Indeed, histological examination of tissues from these developmental time points directly demonstrated a marked increase in mitochondrial activity between the late fetal and early post-natal samples. The genes that were down-regulated in this period suggested de-emphasis of an array of biological functions including Wnt signaling, cell adhesion and differentiation. There were also changes in the expression of genes prior to this late fetal â postnatal transition and between the two postnatal time points that involved a variety of biological functions. It is concluded that there is substantial and coordinated changes in the transcription of a large number of genes in skeletal muscle which underpin the adaption of muscle to the new physiological demands in the postnatal environment. Microarrays were used for transcription profiling of skeletal muscle samples taken from fetal lambs (80, 100, 120 days gestation), new born lambs at birth (150 d) and lambs at 12 weeks (230 d) Sheep used in this experiment were bred from a research flock of Dorset/Suffolk/Rambouillet cross-bred sheep raised at Utah State University and cared for and euthanased for sample collection in accordance with the animal ethics guidelines of Utah State University (Utah, USA). Longissimus dorsi (LD) skeletal muscle samples were taken from fetal lambs at 80, 100 and 120 days of gestation, new born lambs within 1 to 3 days of birth (i.e. 150 days of development) and young lambs at 12 weeks of age (230 days of development). Three individuals were sampled at each developmental time

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Transplanting FVIII/ET3-Secreting Cells in Fetal Sheep Increases FVIII Levels Long-Term Without Inducing Immunity or Toxicity

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