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This Review discusses current approaches to disc regeneration, with a particular focus on cell-based therapeutic strategies, including ongoing challenges, and attempts to provide a framework to interpret current data and guide future investigational studies.Extensive allelic variation in agronomically important genes serves as the basis of rice breeding. Here, we present a comprehensive map of rice quantitative trait nucleotides (QTNs) and inferred QTN effects based on eight genome-wide association study cohorts. Population genetic analyses revealed that domestication, local adaptation and heterosis are all associated with QTN allele frequency changes. A genome navigation system, RiceNavi, was developed for QTN pyramiding and breeding route optimization, and implemented in the improvement of a widely cultivated indica variety. This work presents an efficient platform that bridges ever-increasing genomic knowledge and diverse improvement needs in rice.Naive epiblast and embryonic stem cells (ESCs) give rise to all cells of adults. Such developmental plasticity is associated with genome hypomethylation. Here, we show that LIF-Stat3 signaling induces genomic hypomethylation via metabolic reconfiguration. Stat3-/- ESCs show decreased α-ketoglutarate production from glutamine, leading to increased Dnmt3a and Dnmt3b expression and DNA methylation. Notably, genome methylation is dynamically controlled through modulation of α-ketoglutarate availability or Stat3 activation in mitochondria. Alpha-ketoglutarate links metabolism to the epigenome by reducing the expression of Otx2 and its targets Dnmt3a and Dnmt3b. Genetic inactivation of Otx2 or Dnmt3a and Dnmt3b results in genomic hypomethylation even in the absence of active LIF-Stat3. Stat3-/- ESCs show increased methylation at imprinting control regions and altered expression of cognate transcripts. Single-cell analyses of Stat3-/- embryos confirmed the dysregulated expression of Otx2, Dnmt3a and Dnmt3b as well as imprinted genes. Several cancers display Stat3 overactivation and abnormal DNA methylation; therefore, the molecular module that we describe might be exploited under pathological conditions.Noncoding RNAs are exquisitely titrated by the cellular RNA surveillance machinery for regulating diverse biological processes. The RNA exosome, the predominant 3' RNA exoribonuclease in mammalian cells, is composed of nine core and two catalytic subunits. Here, we developed a mouse model with a conditional allele to study the RNA exosome catalytic subunit DIS3. In DIS3-deficient B cells, integrity of the immunoglobulin heavy chain (Igh) locus in its topologically associating domain is affected, with accumulation of DNA-associated RNAs flanking CTCF-binding elements, decreased CTCF binding to CTCF-binding elements and disorganized cohesin localization. DIS3-deficient B cells also accumulate activation-induced cytidine deaminase-mediated asymmetric nicks, altering somatic hypermutation patterns and increasing microhomology-mediated end-joining DNA repair. Altered mutation patterns and Igh architectural defects in DIS3-deficient B cells lead to decreased class-switch recombination but increased chromosomal translocations. Our observations of DIS3-mediated architectural regulation at the Igh locus are reflected genome wide, thus providing evidence that noncoding RNA processing is an important mechanism for controlling genome organization.Fibrosis is a common pathological response to inflammation in many peripheral tissues and can prevent tissue regeneration and repair. Here, we identified persistent fibrotic scarring in the CNS following immune cell infiltration in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Using lineage tracing and single-cell sequencing in EAE, we determined that the majority of the fibrotic scar is derived from proliferative CNS fibroblasts, not pericytes or infiltrating bone marrow-derived cells. Ablating proliferating fibrotic cells using cell-specific expression of herpes thymidine kinase led to an increase in oligodendrocyte lineage cells within the inflammatory lesions and a reduction in motor disability. We further identified that interferon-gamma pathway genes are enriched in CNS fibrotic cells, and the fibrotic cell-specific deletion of Ifngr1 resulted in reduced fibrotic scarring in EAE. These data delineate a framework for understanding the CNS fibrotic response.Myeloid-derived suppressor cells (MDSCs) are pathologically activated neutrophils and monocytes with potent immunosuppressive activity. They are implicated in the regulation of immune responses in many pathological conditions and are closely associated with poor clinical outcomes in cancer. Recent studies have indicated key distinctions between MDSCs and classical neutrophils and monocytes, and, in this Review, we discuss new data on the major genomic and metabolic characteristics of MDSCs. AR-13324 We explain how these characteristics shape MDSC function and could facilitate therapeutic targeting of these cells, particularly in cancer and in autoimmune diseases. Additionally, we briefly discuss emerging data on MDSC involvement in pregnancy, neonatal biology and COVID-19.Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative option in MF. There is no consensus on the optimal conditioning regimen. We report outcomes of 187 patients with MF transplanted between 2010 and 2017 conditioned with TBF. Median age was 58 years. Median interval from diagnosis to allo-HCT was 44 months. Donors were haploidentical (41%), unrelated (36%) or HLA-identical siblings (23%). Stem cell source was PB in 60%. Conditioning was myeloablative in 48% of cases. Antithymocyte globulin (ATG) was used in 41% of patients. At 100 days, neutrophil and platelet engraftment were 91% and 63% after a median of 21 and 34 days, respectively. Grade II-IV and III-IV acute GVHD occurred in 24% and 12%, while at 3 years, all grade chronic GVHD and chronic extensive GVHD had been diagnosed in 38% and 11%. At 3 years, OS, RFS and GRFS were 55%, 49% and 43%, respectively. RI and NRM were 17% and 33%. On multivariate analysis, poor KPS and the use of unrelated donors were associated with worse GRFS and a higher grade II-IV acute GVHD, respectively.