Περίληψη:
Previous microarray analyses of RNAs from 8-cell (8C) human embryos revealed a lack of cell cycle checkpoints and overexpression of core circadian oscillators and cell cycle drivers relative to pluripotent human stem cells [human embryonic stem cells/induced pluripotent stem (hES/iPS)] and fibroblasts, suggesting growth factor independence during early cleavage stages. To explore this possibility, we queried our combined microarray database for expression of 487 growth factors and receptors. Fifty-one gene elements were overdetected on the 8C arrays relative to hES/iPS cells, including 14 detected at least 80-fold higher, which annotated to multiple pathways: six cytokine family (CSF1R, IL2RG, IL3RA, IL4, IL17B, IL23R), four transforming growth factor beta (TGFB) family (BMP6, BMP15, GDF9, ENG), one fibroblast growth factor (FGF) family [FGF14(FH4)], one epidermal growth factor member (GAB1), plus CD36, and CLEC10A. 8C-specific gene elements were enriched (73%) for reported circadian-controlled genes in mouse tissues. High-level detection of CSF1R, ENG, IL23R, and IL3RA specifically on the 8C arrays suggests the embryo plays an active role in blocking immune rejection and is poised for trophectoderm development; robust detection of NRG1, GAB1,-2, GRB7, and FGF14(FHF4) indicates novel roles in early development in addition to their known roles in later development. Forty-four gene elements were underdetected on the 8C arrays, including 11 at least 80-fold under the pluripotent cells: two cytokines (IFITM1, TNFRSF8), five TGFBs (BMP7, LEFTY1, LEFTY2, TDGF1, TDGF3), two FGFs (FGF2, FGF receptor 1), plus ING5, and WNT6. The microarray detection patterns suggest that hES/iPS cells exhibit suppressed circadian competence, underexpression of early differentiation markers, and more robust expression of generic pluripotency genes, in keeping with an artificial state of continual uncommitted cell division. In contrast, gene expression patterns of the 8C embryo suggest that it is an independent circadian rhythm-competent equivalence group poised to signal its environment, defend against maternal immune rejection, and begin the rapid commitment events of early embryogenesis. © 2015 Antonis Vlismas, et al.
Συγγραφείς:
Vlismas, A.
Bletsa, R.
Mavrogianni, D.
Mamali, G.
Pergamali, M.
Dinopoulou, V.
Partsinevelos, G.
Drakakis, P.
Loutradis, D.
Kiessling, A.A.
Λέξεις-κλειδιά:
bone morphogenetic protein 15; bone morphogenetic protein 6; CD36 antigen; colony stimulating factor receptor; endoglin; fibroblast growth factor 14; fibroblast growth factor receptor 1; fibroblast growth factor receptor 2; growth differentiation factor 9; growth factor; growth factor receptor; growth factor receptor bound protein 2; growth factor receptor bound protein 7; insulin receptor; interleukin 2 receptor gamma; interleukin 23 receptor; interleukin 3 receptor; interleukin 4; left right determination factor 1; left right determination factor 2; nerve growth factor; neu differentiation factor; osteogenic protein 1; platelet derived growth factor; platelet derived growth factor receptor; teratocarcinoma derived growth factor 1; teratocarcinoma derived growth factor 3; unclassified drug; vasculotropin; Wnt6 protein; fibroblast growth factor, animal experiment; animal tissue; Article; cell cycle checkpoint; cell differentiation; cell division; circadian rhythm; controlled study; ectoderm; embryo development; embryonic stem cell; female; fibroblast; gene expression; gene overexpression; genetic analysis; human; human cell; human embryonic stem cell; immune response; microarray analysis; nonhuman; pluripotent stem cell; priority journal; protein expression; cell culture; cell cycle; cytology; DNA microarray; human embryonic stem cell; metabolism; physiology; pluripotent stem cell; pregnancy; tissue microarray, Cell Cycle; Cell Differentiation; Cell Division; Cells, Cultured; Female; Fibroblast Growth Factors; Fibroblasts; Gene Expression; Human Embryonic Stem Cells; Humans; Oligonucleotide Array Sequence Analysis; Pluripotent Stem Cells; Pregnancy; Tissue Array Analysis
