Rolling uphill: in vivo reacquisition of pluripotency during cranial neural crest differentiation

Conrad Waddington famously used his epigenetic landscape to describe the paths a cell might take during developmental differentiation. In this analogy, the undifferentiated stem cell begins at the highest elevation and proceeds to tumble downward towards its final resting place, representing terminal differentiation. This general concept elegantly captures the essence of developmental transitions, but recent single-cell studies by Dr. Joanna Wysocka’s research group indicate that an alternative strategy underlies development of cranial neural crest cells. Published in Science, Antoine Zalc, Rahul Sinha and colleagues discovered that ectoderm-derived cranial neural crest cells undergo a developmental reprogramming event in vivo, expanding their differentiation potential through the reactivation of pluripotency, in effect rolling backwards up Waddington’s development landscape before eventually differentiating into mesenchymal lineages.