Unknown,Transcriptomics,Genomics,Proteomics

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FGF2 sustains NANOG and switches the outcome of BMP4 induced human embryonic stem cell differentiation

ABSTRACT: NANOG has emerged as a central gatekeeper of pluripotency. Here we show that as human embryonic stem (ES) cells exit the pluripotent state, NANOG can play a key role in determining lineage outcome. It has previously been reported that BMPs can induce differentiation of human ES cells into extraembryonic lineages. Here we report that FGF2 switches BMP4 induced differentiation outcome to mesendoderm, characterized by the uniform expression of T (brachyury) and other primitive streak markers. Blocking the MEK-ERK pathway either by chemical inhibitors or by an ERK-specific phosphatase (DUSP6) blocks the FGF2-mediated lineage switch. Active MEK-ERK signaling prolongs NANOG expression during BMP-induced differentiation. Forced NANOG expression results in FGF independent BMP4 induction of mesendoderm, and knockdown of NANOG greatly reduces T induction. Together, our results demonstrate that FGF2 signaling switches the outcome of BMP4 induced differentiation of human ES cells by maintaining NANOG levels through the MEK-ERK pathway. There are three sets of expression data. Set 1 (14 samples) is 5day human ES cells (H1) differentiated with different concentrations of BMP4, in the presence or absence of FGF2. Set 2 (14 samples) is 50ng/mL of BMP4 induced H1 cells differentiation time course, with or without FGF2. Set 3 (22 samples) is 5ng/mL of BMP4 induced H1 cells differentiation time course, with or without FGF2.

ORGANISM(S): Homo sapiens

SUBMITTER: James Thomson

PROVIDER: E-GEOD-25973 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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