Hypoxia inhibits myogenic differentiation of the mouse cell line C2C12 and primary mouse satellite cells, and also inhibits neuronal differentiation of primary neuronal stem cells derived from the embryonic rat cortex. The inhibitory effect of hypoxia on cellular differentiation is dependent on hypoxia-inducible factor 1-alpha (Hif1a) and transcriptional activity of the Notch intracellular domain, NICD. The half-life of NICD1 is prolonged by hypoxia, and this increased stability of NICD1 is dependent on Hif1a. A recombinant mouse NICD1 (mNICD1) and a recombinant human HIF1A interact in vitro. Cotransfection of mNICD1 and HIF1A into mouse embryonic teratocarcinoma cell line P19 results in increased transcription from a Notch target promoter.