Chromatin-state barriers enforce an irreversible mammalian cell fate decision

• DOI: 10.1016/j.celrep.2021.109967
• Publication Date: 2021-11-09T17:51:59Z
• Authors: M. Andrés Blanco; David B. Sykes; Lei Gu; Mengjun Wu; Ricardo Petroni; Rahul Karnik; Mathias Wawer; Joshua Rico; Haitao Li; William D. Jacobus; Ashwini Jambhekar; Sihem Cheloufi; Alexander Meissner; Konrad Hochedlinger; David T. Scadden; Yang Shi
• Keywords: Cell fate determination

Stem and progenitor cells have the capacity to balance self-renewal differentiation. Hematopoietic myeloid progenitors replenish more than 25 billion terminally differentiated neutrophils every day under homeostatic conditions can increase this output in response stress or infection. At what point along spectrum of maturation do lose for become irreversibly committed differentiation? Using a system conditional development that be toggled between differentiation, we interrogate determinants "point no return" differentiation commitment. Irreversible commitment is due primarily loss open regulatory site access disruption positive feedback transcription factor activation loop. Restoration loop extends window cell plasticity alters return. These findings demonstrate how chromatin state enforces perpetuates fate identify potential avenues manipulating identity.