Alpha-5 Laminin and Self-Renewal

 α-5 Laminin Synthesized by Human Pluripotent Stem Cells Promotes Self-Renewal

Laperle A., Hsiao C., Lampe M., Mortier J., Saha K., Palecek S.P., Masters K.S., Stem Cell Reports 2015

The authors study the role of endogenously produced extracellular matrix (ECM) components in regulating hPSC fates. They identify α-5 laminin as a signature ECM component endogenously synthesized by undifferentiated hESC and hiPSC cultured on defined substrates. Knockdown and disruption of the LAMA5 gene dramatically reduced hPSC self-renewal and increased apoptosis without affecting the expression of pluripotency markers. Self-renewal and survival was restored to wild-type levels by culturing the LAMA5-deficient cells on exogenous laminin-521. Synthemax or Vitronectin could not restore survival. Treatment of LAMA5-deficient cells with blebbistatin or a ROCK inhibitor partially restored self-renewal and diminished apoptosis. These results demonstrate that endogenous α-5 laminin promotes hPSC survival and self-renewal in an autocrine and paracrine manner.