CD74 is a cell-surface receptor for the cytokine macrophage migration inhibitory factor. Macrophage migration inhibitory factor binding to CD74 induces its intramembrane cleavage and the release of its cytosolic intracellular domain (CD74-ICD), which regulates cell survival. In the present study, we characterized the transcriptional activity of CD74-ICD in chronic lymphocytic B cells. We show that following CD74 activation, CD74-ICD interacts with the transcription factors RUNX (Runt related transcription factor) and NF-κB and binds to proximal and distal regulatory sites enriched for genes involved in apoptosis, immune response, and cell migration. This process leads to regulation of expression of these genes. Our results suggest that identifying targets of CD74 will help in understanding of essential pathways regulating B-cell survival in health and disease.CD74 | transcription | CLL | NF-κB | RUNX

Plants continuously form new organs in different developmental contexts in response to environmental cues. Underground lateral roots initiate from prepatterned cells in the main root, but cells can also bypass the root-shoot trajectory separation and generate shoot-borne roots through an unknown mechanism. We mapped tomato ( Solanum lycopersicum ) shoot-borne root development at single-cell resolution and showed that these roots initiate from phloem-associated cells through a unique transition state. This state requires the activity of a transcription factor that we named SHOOTBORNE ROOTLESS ( SBRL ) . Evolutionary analysis reveals that SBRL ’s function and cis regulation are conserved in angiosperms and that it arose as an ancient duplication, with paralogs controlling wound-induced and lateral root initiation. We propose that the activation of a common transition state by context-specific regulators underlies the plasticity of plant root systems.

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During plant post-embryonic growth new meristems and associated stem cells form in different development contexts in order to respond to environmental cues. While underground lateral roots initiate from designated cells in the main root, an unknown mechanism allows cells to bypass the root/shoot identity trajectory and generate shoot-borne-roots. Using single-cell profiling of tomato (Solanum lycoperiscum) stems we isolated a rare transient cell population that serve as progenitors for shoot-borne-root meristems. Analysis of this population identified a transcription factor required for the formation of shoot-borne-roots which we named SHOOT BORNE ROOTLESS (SBRL). Evolutionary analysis revealed that SBRL function is deeply conserved in angiosperms and that it arose as part of an ancient duplicated superlocus, only lost in root-less plants, containing both shoot-borne and lateral root initiation regulators. We propose that the ability to activate a common transition state with context-specific regulators allows the remarkable developmental plasticity found in plants.One Sentence SummaryHighly conserved superlocus of LBD genes, acting within an early transition identity, regulates shoot-borne and lateral root formation.

Hematopoietic stem and progenitor cells (HSPCs) are a small population of undifferentiated cells that have the capacity for self-renewal and differentiate into all blood cell lineages. These cells are the most useful cells for clinical transplantations and for regenerative medicine. So far, it has not been possible to expand adult hematopoietic stem cells (HSCs) without losing their self-renewal properties. CD74 is a cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF), and its mRNA is known to be expressed in HSCs. Here, we demonstrate that mice lacking CD74 exhibit an accumulation of HSCs in the bone marrow (BM) due to their increased potential to repopulate and compete for BM niches. Our results suggest that CD74 regulates the maintenance of the HSCs and CD18 expression. Its absence leads to induced survival of these cells and accumulation of quiescent and proliferating cells. Furthermore, in in vitro experiments, blocking of CD74 elevated the numbers of HSPCs. Thus, we suggest that blocking CD74 could lead to improved clinical insight into BM transplant protocols, enabling improved engraftment.