Heparan Sulfation Dependent FGF Signalling Maintains ES Cells Primed for Differentiation in a Heterogeneous State

ABSTRACT: Embryonic stem (ES) cells continuously decide whether to maintain pluripotency or differentiate. While exogenous LIF and BMP4 perpetuate a pluripotent state, less is known about factors initiating differentiation. We show that heparan sulfate (HS) proteoglycans are critical co-receptors for signals inducing ES cell differentiation. Genetic targeting of NDST1 and 2, two enzymes required for N-sulfation of proteoglycans, blocked differentiation. This phenotype was rescued by HS presented in trans or by soluble heparin. NaClO3-, which reduces sulfation of proteoglycans, potently blocked differentiation of wild type cells. Mechanistically, N-sulfation was identified to be critical for functional autocrine FGF4 signalling. Micro array analysis identified the pluripotency maintaining transcripti

ORGANISM(S): Mus musculus

SUBMITTER: Lorenz Poellinger 

PROVIDER: E-GEOD-15974 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress