Melania Barile

Abstract A defining characteristic of all metazoan organisms is the existence of different cell states or cell types, driven by changes in gene expression kinetics, principally transcription, splicing and degradation rates. The RNA velocity framework utilizes both spliced and unspliced reads in sin- gle cell mRNA preparations to predict future cellular states and estimate transcriptional kinetics.

Abstract Recent lineage tracing single-cell techniques (LT-scSeq), e.g., the Lineage And RNA RecoverY (LARRY) barcoding system, have enabled clonally resolved interpretation of differentiation trajectories. However, the heterogeneity of clone-specific kinetics remains understudied, both quantitatively and in terms of interpretability, thus limiting the power of bar-coding systems to unravel how heterogeneous stem cell clones drive overall cell population dynamics.

Highlights • Unperturbed hematopoiesis can be sustained long term while the HSC pool is depleted • CITED2 promotes HSC survival but not quiescence under homeostatic conditions • CITED2 maintains the HSC pool by controlling Mcl1 and Pten expression Summary Hematopoietic stem cells (HSCs) reside at the apex of the hematopoietic differentiation hierarchy and sustain multilineage hematopoiesis. Here, we show that the transcriptional regulator CITED2 is essential for life-long HSC maintenance.