- Fumarate hydratase is a critical metabolic regulator of hematopoietic stem cell functions
Guitart et al. performed an in vivo genetic dissection of the Krebs cycle enzyme fumarate hydratase (Fh1) in the hematopoietic system. Their investigations revealed multifaceted functions of Fh1 in the regulation of hematopoietic stem cell biology and leukemic transformation.
- 27-Hydroxycholesterol impairs neuronal glucose uptake through an IRAP/GLUT4 system dysregulation
Ismail et al. show that 27-hydroxycholesterol, a peripheral cholesterol metabolite capable of passing the blood–brain barrier, reduces brain glucose uptake by upregulating the renin-angiotensin system and inhibiting GLUT4. This alteration affects memory processes and is likely to have implications on neurodegenerative diseases.
- RUNX1 cooperates with FLT3-ITD to induce leukemia
Behrens et al. establish the interplay of activated FLT3 receptor and the phosphorylated RUNX1 transcription factor in uncoupling proliferation and differentiation signals in acute leukemia. These findings demonstrate that RUNX1 is a viable therapeutic target in FLT3-mutated AML.
- Conserved IKAROS-regulated genes associated with B-progenitor acute lymphoblastic leukemia outcome
Analysis of mouse and human B lineage acute lymphoblastic leukemia identifies evolutionarily conserved targets of the tumor-suppressive transcription factor IKAROS, implicating CTNND1 in leukemia maintenance.
- Genetic analysis of Ikaros target genes and tumor suppressor function in BCR-ABL1+ pre–B ALL
Schjerven et al. compare mouse and human models of pre–B ALL to define conserved target genes and pathways of the tumor suppressor Ikaros, revealing CTNND1 and the early hematopoietic cell-surface receptors SPN (CD43) and CD34 as novel Ikaros targets that each confer oncogenic growth advantage.
- Neuronal CTGF/CCN2 negatively regulates myelination in a mouse model of tuberous sclerosis complex
One of the brain manifestations of tuberous sclerosis complex (TSC) is reduced myelination, but the underlying mechanism remains unclear. Ercan et al. demonstrate that mutant neurons overexpress a protein, connective tissue growth factor (CTGF), which impairs oligodendrocyte maturation and myelination.
- The Eph-related tyrosine kinase ligand Ephrin-B1 marks germinal center and memory precursor B cells
Laidlaw et al. show that Ephrin-B1 is a specific marker of mature germinal center (GC) B cells. Use of Ephrin-B1 allows for the identification of phenotypically distinct GC B cell subsets, including a population that may represent memory precursor B cells.
- Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer
Öhlund et al. develop a three-dimensional co-culture platform of neoplastic pancreatic ductal organoids and pancreatic stellate cells (PSCs) to characterize the dynamic crosstalk between cancer cells and stromal cells, and to address stromal heterogeneity. The co-cultures reveal the co-existence of two phenotypically distinct populations of PSCs, providing insights into PDA biology and prompting a reconsideration of interventional strategies.
- RAG1/2 induces genomic insertions by mobilizing DNA into RAG1/2-independent breaks
Rommel et al. reveal a novel RAG1/2-mediated insertion pathway, which has the potential to destabilize the lymphocyte genome and shares features with DNA insertions observed in human cancer.
- Soluble TREM2 induces inflammatory responses and enhances microglial survival
Zhong et al. describe two novel roles for soluble TREM2 (sTREM2) in regulation of proinflammatory responses and prevention of cellular apoptosis in microglia.