- Myeloid tumor suppressor role for NOL3
Stanley et al. show that loss of Nol3 in mice leads to a myeloproliferative phenotype resembling primary myelofibrosis, with activation of JAK–STAT signaling and significant cellular and molecular resemblance to human disease. These findings provide a novel role for Nol3 in hematopoiesis and myeloid malignancies.
- Fli1 regulates immune tolerance and homeostasis
Takahashi et al. find that epithelial cell–conditional knockdown of transcription factor Fli1 in mice drives systemic autoimmunity derived from thymic defects as well as selective tissue fibrosis in the skin and esophagus, mimicking human scleroderma. This study unravels the unanswered question about the origin of autoimmunity and selective tissue fibrosis in this disease.
- Fibroblast heterogeneity 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.
- RUNX1 oncogenic function in AML
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.
- sTREM2 regulates microglial viability and function
Zhong et al. describe two novel roles for soluble TREM2 (sTREM2) in regulation of proinflammatory responses and prevention of cellular apoptosis in microglia.
- 27-OH impairs neuronal glucose uptake
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.
- Fh1 is essential for HSC 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.