LIN28 is an RNA-binding protein that is best known for its roles in promoting pluripotency via regulation of the microRNA let-7. However, recent studies have uncovered new roles for LIN28 and have revealed how it functions, suggesting that it is more than just a regulator of miRNA biogenesis. Together, these findings imply a new paradigm for LIN28 -as a gatekeeper molecule that regulates the transition between pluripotency and committed cell lineages, in both let-7-dependent and let-7-independent manners. Here, we provide an overview of LIN28 function in development and disease.

The RNA-binding protein LIN28 is known to regulate cell fate, tissue growth, and pluripotency; however, a unified understanding of its role at the cellular level has not been achieved. Here, we address its developmental activity in mammalian postnatal neurogenesis. Constitutive expression of LIN28 in progenitor cells of the mouse subventricular zone (SVZ) caused several distinct effects: 1 ) the number of differentiated neurons in the olfactory bulb was dramatically reduced, whereas the relative abundance of 2 neuronal subtypes was significantly altered, 2 ) the population of proliferating neural progenitors in the SVZ was reduced, whereas the proportion of neuroblasts was increased, and 3 ) the number of astrocytes was reduced, occasionally causing them to appear early. Thus, LIN28 acts at a poststem cell/predifferentiation step, and its continuous expression caused a precocious phenotype unlike in other experimental systems. Furthermore, for the first time in a vertebrate system, we separate the majority of the biologic role of LIN28 from its known activity of blocking the microRNA let-7 by using a circular RNA sponge. We find that although LIN28 has a multifaceted role in the number and types of cells produced during postnatal neurogenesis, it appears that its action through let-7 is responsible for only a fraction of these effects.—Romer-Seibert, J. S., Hartman, N. W., Moss, E. G. The RNA-binding protein LIN28 controls progenitor and neuronal cell fate during postnatal neurogenesis.

Purpose of review Clonal heterogeneity is a significant obstacle to successful treatment of patients with acute myeloid leukemia (AML). Here, we review new advances in the understanding of genetic heterogeneity in AML using single-cell DNA-sequencing technology. Recent findings New genomics and immunologic discovery tools have provided single-cell resolution maps of the clonal architecture of AML. The use of these technologies reveals the mutational landscape of AML at diagnosis, during treatment, and at relapse has an enormous degree of clonal complexity and diversity that is poised to adapt and evolve under environmental pressures. Summary AML is a complex ecosystem of competing and cooperating clones undergoing constant evolution and selection.

The authors have declared no conflicts of interest for this article.