M1-type microglia can induce astrocytes to deposit chondroitin sulfate proteoglycan after spinal cord injury

After spinal cord injury(SCI),astrocytes gradually migrate to and surround the lesion,depositing chondroitin sulfate proteoglycan-rich extracellular matrix and forming astrocytic scar,which limits the spread of inflammation but hinders axon regeneration.Meanwhile,microglia gradually accumulate at the lesion border to form microglial scar and can polarize to generate a pro-inflammatory M1 phenotype or an anti-inflammatory M2 phenotype.However,the effect of microglia polarization on astrocytes is unclear.Here,we found that both microglia(CX3 CR1^(+))and astrocytes(GFAP^(+))gathered at the lesion border at 14 days post-injury(dpi).The microglia accumulated along the inner border of and in direct contact with the astrocytes.M1-type microglia(i NOS^(+)CX3 CR1^(+))were primarily observed at 3 and 7 dpi,while M2-type microglia(Arg1^(+)CX3 CR1^(+))were present at larger numbers at 7 and 14 dpi.Transforming growth factor-β1(TGFβ1)was highly expressed in M1 microglia in vitro,consistent with strong expression of TGFβ1 by microglia in vivo at 3 and 7 dpi,when they primarily exhibited an M1 phenotype.Furthermore,conditioned media from M1-type microglia induced astrocytes to secrete chondroitin sulfate proteoglycan in vitro.This effect was eliminated by knocking down sex-determining region Y-box 9(SOX9)in astrocytes and could not be reversed by treatment with TGFβ1.Taken together,our results suggest that microglia undergo M1 polarization and express high levels of TGFβ1 at 3 and 7 dpi,and that M1-type microglia induce astrocytes to deposit chondroitin sulfate proteoglycan via the TGFβ1/SOX9 pathway.The study was approved by the Institutional Animal Care and Use Committee of Anhui Medical University,China(approval No.LLSC20160052)on March 1,2016.

SOX13 gene downregulation in peripheral blood mononuclear cells of patients with Klinefelter syndrome

Klinefelter syndrome(KS)is the most common sex chromosome disorder in men.It is characterized by germ cell loss and other variable clinical features,including autoimmunity.The sex-determining region of Y(SRY)-box 13(Sox13)gene is expressed in mouse spermatogonia.In addition,it has been identified as islet cell autoantigen 12(ICA12),which is involved in the pathogenesis of autoimmune diseases,including type 1 diabetes mellitus(DM)and primary biliary cirrhosis.SOX13 expression has never been investigated in patients with KS.In this age-matched,case-control study performed on ten patients with KS and ten controls,we found that SOX13 is significantly downregulated in peripheral blood mononuclear cells of patients with KS compared to controls.This finding might be consistent with the germ cell loss typical of patients with KS.However,the role of SOX13 in the pathogenesis of germ cell loss and humoral autoimmunity in patients with KS deserves to be further explored.

Emerging signals regulating liver tumor initiating cells

Tumor initiating cells(TICs)have been identified as cells that account for tumor heterogeneity.Recent studies demonstrated that genes controlling stem cell biology play key roles in maintaining TICs and promote their development into cancer.In this review,we summarize findings from human and animal studies that indicate the presence of TICs during liver cancer development.Markers identified for liver development and regeneration are used to identify liver cancer TICs.Expression of these markers is often upregulated in human hepatocellular carcinoma(HCC)specimen.Using flow cytometry analysis and lineage tracing approaches,the presence of TICs is confirmed.Expression of TIC markers and the presence of TICs are also observed in genetically modified animals that target genes that are frequently altered in human HCC.The presence of these TICs represents a major challenge for therapeutic development.Elucidating signals that can regulate the fate,transformation and growth of liver TICs is an emerging need in liver research.Sex-determining region Y-box 9(SOX9)has recently become an important marker for liver TICs.Here,we summarize the role of SOX9 in TICs and its potential interaction with other signals.This includes the Notch-Numb signal that controls asymmetrical-symmetrical cell division,Wnt-b-catenin signal that maintains cell fate and transforming growth factor(TGF)-b signal that acts as upstream inducers.