Stem cells balance their self-renewal with their differentiation into mature cells. An intriguing question is when during the process of maturation a progenitor cell reaches a point of no return, losing its capacity to self-renew and becoming committed to generating a specific cell type. Ludwig Oxford’s Yang Shi and colleagues reported in a paper published in November in Cell Reports that a combination of remodeling of chromatin structure, activation of gene control elements (enhancers) and changes in transcription factor usage contribute to an irreversible commitment to differentiation. The researchers examined how progenitor cells become committed to the production of terminally differentiated neutrophils, a type of white blood cell, from blood stem cells known as hematopoietic myeloid progenitors. They found that the changes they identified result in reduced accessibility to regulatory DNA sites and disruption of a positive feedback transcription factor activation loop that prevents differentiation. The new findings have relevance for acute myeloid leukemia (AML), in which differentiation is arrested. By helping to define the molecular processes involved in differentiation, the researchers hope to identify targets against which to develop new AML therapies.
This article appeared in the February 2022 issue of Ludwig Link. Click here to download a PDF (1 MB).