title: Low-oxygen tension and IGF-I promote proliferation and multipotency of placental mesenchymal stem cells (PMSCs) from different gestations via distinct signaling pathways.
abstract: The microenvironment of placental mesenchymal stem cells (PMSCs) is dynamic throughout gestation and determines changes in cell fate. In vivo, PMSCs initially develop in low-oxygen tension and low IGF-I concentrations, and both increase gradually with gestation. The impact of varying concentrations of IGF-I and changing oxygen tension on PMSC signaling and multipotency was investigated in PMSCs from early (preterm) and late (term) gestation human placentae. Preterm PMSCs had greater proliferative response to IGF-I, which was further enhanced by low-oxygen tension. Low-oxygen tension alone was sufficient to induce ERK1/2 phosphorylation, whereas IGF-I was required for AKT (protein kinase B) phosphorylation. Low-oxygen tension prolonged ERK1/2 and AKT phosphorylation with a slowed phosphorylation decay even in presence of IGF-I. Low-oxygen tension maintained higher levels of IGF-I receptor and insulin receptor substrate 1 that were otherwise decreased by exposure to IGF-I and induced a differential phosphorylation pattern on IGF-I receptorβ and insulin receptor substrate 1. Phosphorylation of ERK1/2 and AKT was different between the preterm and term PMSCs, and phospho-AKT, and not phospho-ERK1/2, was the major determinant of PMSC proliferation and octamer-4 levels. These studies demonstrate that low-oxygen tension regulates the fate of PMSCs from early and late gestations in response to IGF-I, both independently and dependently, via specific signal transduction mechanisms.
authors: Departments of Biochemistry (A.Y., V.K.M.H.) and Paediatrics (C.I., V.K.M.H.), Schulich School of Medicine and Dentistry; Children's Health Research Institute (A.Y., C.I., V.K.M.H.); and Lawson Health Research Institute (A.Y., C.I., V.K.M.H.); Western University, London, Ontario, Canada N6C 2V5.
authors: Amer
authors: A
authors: Youssef
authors: Cristiana
authors: C
authors: Iosef
authors: Victor K M
authors: VK
authors: Han
mesh_terms: D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010766:Phosphorylation; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D007334:Insulin-Like Growth Factor I; D011505:Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D010100:Oxygen