Group 2 innate lymphoid cells(ILC2s)play important tissue resident roles in anti-parasite immunity,allergic immune response,tissue homeostasis,and tumor immunity.ILC2s are considered tissue resident cells with little ...Group 2 innate lymphoid cells(ILC2s)play important tissue resident roles in anti-parasite immunity,allergic immune response,tissue homeostasis,and tumor immunity.ILC2s are considered tissue resident cells with little proliferation at steady state.Recent studies have shown that a subset of small intestinal ILC2s could leave their residing tissues,circulate and migrate to different organs,including lung,liver,mesenteric LN and spleen,upon activation.However,it remains unknown whether other ILC populations with migratory behavior exist.In this study,we find two major colon ILC2 populations with potential to migrate to the lung in response to IL-25 stimulation.One subset expresses IL-17A and resembles inflammatory ILC2s(iILC2s)but lacks CD27 expression,whereas the other expresses CD27 but not IL-17A.In addition,the IL-17A^(+)ILC2s express lower levels of CD127,CD25,and ST2 than CD27^(+)ILC2s,which express higher levels of IL-5 and IL-13.Surprisingly,we found that both colon ILC2 populations still maintained their colonic features of preferential expression of IL-17A and CD27,IL-5/IL-13,respectively.Together,our study identifies two migratory colon ILC2 subsets with unique surface markers and cytokine profiles which are critical in regulating lung and colon immunity and homeostasis.展开更多
The Chouchani lab recently reported in Nature that a dynamic intracellular lactate is a physiological regulator for cell cycle progress.They also showed that accumulated lactate in cell mitosis directly binds and inhi...The Chouchani lab recently reported in Nature that a dynamic intracellular lactate is a physiological regulator for cell cycle progress.They also showed that accumulated lactate in cell mitosis directly binds and inhibits Sentrin/SUMO-specific pro-tease 1 to enrich SUMO2/3-modification of anaphase-promot-ing complex 4(APC4),which promotes the degradation of APC/C complexes,leading to mitosis exit.展开更多
Transplantation of oligodendrocyte progenitor cells (OPCs) is a promising way for treating demyelinating diseases. However, generation of scalable and autologous sources of OPCs has proven difficult. We previously est...Transplantation of oligodendrocyte progenitor cells (OPCs) is a promising way for treating demyelinating diseases. However, generation of scalable and autologous sources of OPCs has proven difficult. We previously established a chemical condition M9 that could specifically initiate neural program in mouse embryonic fibroblasts. Here we found that M9 could induce the formation of colonies that undergo mesenchymal-to-epithelial transition at the early stage of reprogramming. These colonies may represent unstable and neural lineage-restricted intermediates that have not established a neural stem cell identity. By modulating the culture signaling recapitulating the principle of OPC development, these intermediate cells could be reprogrammed towards OPC fate. The chemical-induced OPC-like cells (ciOPLCs) resemble primary neural stem cell-derived OPCs in terms of their morphology, gene expression, and the ability of self-renewal. Upon differentiation, ciOPLCs could produce functional oligodendrocytes and myelinate the neuron axons in vitro, validating their OPC identity molecularly and functionally. Therefore, our study provides a non-integrating approach to OPC reprogramming that may ultimately provide an avenue to patient-specific cell-based or in situ regenerative therapy.展开更多
Microtubules (MTs) are regulated by a number of known posttranslational modifications (PTMs) on α/β-tubulin to fulfill diverse cellular functions. Here, we showed that SUMOylation is a novel PTM on α-tubulin in viv...Microtubules (MTs) are regulated by a number of known posttranslational modifications (PTMs) on α/β-tubulin to fulfill diverse cellular functions. Here, we showed that SUMOylation is a novel PTM on α-tubulin in vivo and in vitro. The SUMOylation on α-tubulin mainly occurred at Lys 96 (K96), K166, and K304 of soluble α-tubulin and could be removed by small ubiquitin-related modifier (SUMO)-specific peptidase 1. In vitro experiments showed that tubulin SUMOylation could reduce interprotofilament interaction, promote MT catastrophe, and impede MT polymerization. In cells, mutation of the SUMOylation sites on α-tubulin reduced catastrophe frequency and increased the proportion of polymerized α-tubulin, while upregulation of SUMOylation with fusion of SUMO1 reduced α-tubulin assembly into MTs. Additionally, overexpression of SUMOylation-deficient α-tubulin attenuated the neurite extension in Neuro-2a cells. Thus, SUMOylation on α-tubulin represents a new player in the regulation of MT properties.展开更多
Dear Editor,Mucin 1(MUC1)contains N-and C-subunit that forms a heterodimer on the apical surface of luminal epithelial cells.Nevertheless,MUC1 is aberrantly overexpressed in various cancers,such as breast cancer,lung ...Dear Editor,Mucin 1(MUC1)contains N-and C-subunit that forms a heterodimer on the apical surface of luminal epithelial cells.Nevertheless,MUC1 is aberrantly overexpressed in various cancers,such as breast cancer,lung cancer,and prostatic cancer,which critically contributes to tumorigenesis and poor clinical outcomes.1 Several strategies have been developed for targeted-inhibition of MUC1 including vaccines,monoclonal antibodies(MAb),and polypeptide.展开更多
基金supported by the National Natural Science Foundation of China(31930035,91942311,32061143028)Shanghai Science and Technology Commission(20410714000)+1 种基金the National Key Research and Developmental Program of China(2021YFA1301400)generous support from Flow cytometry Core and Sequencing Core at Shanghai Institute of Immunology and animal facility of Shanghai Jiao Tong University School of Medicine。
文摘Group 2 innate lymphoid cells(ILC2s)play important tissue resident roles in anti-parasite immunity,allergic immune response,tissue homeostasis,and tumor immunity.ILC2s are considered tissue resident cells with little proliferation at steady state.Recent studies have shown that a subset of small intestinal ILC2s could leave their residing tissues,circulate and migrate to different organs,including lung,liver,mesenteric LN and spleen,upon activation.However,it remains unknown whether other ILC populations with migratory behavior exist.In this study,we find two major colon ILC2 populations with potential to migrate to the lung in response to IL-25 stimulation.One subset expresses IL-17A and resembles inflammatory ILC2s(iILC2s)but lacks CD27 expression,whereas the other expresses CD27 but not IL-17A.In addition,the IL-17A^(+)ILC2s express lower levels of CD127,CD25,and ST2 than CD27^(+)ILC2s,which express higher levels of IL-5 and IL-13.Surprisingly,we found that both colon ILC2 populations still maintained their colonic features of preferential expression of IL-17A and CD27,IL-5/IL-13,respectively.Together,our study identifies two migratory colon ILC2 subsets with unique surface markers and cytokine profiles which are critical in regulating lung and colon immunity and homeostasis.
文摘The Chouchani lab recently reported in Nature that a dynamic intracellular lactate is a physiological regulator for cell cycle progress.They also showed that accumulated lactate in cell mitosis directly binds and inhibits Sentrin/SUMO-specific pro-tease 1 to enrich SUMO2/3-modification of anaphase-promot-ing complex 4(APC4),which promotes the degradation of APC/C complexes,leading to mitosis exit.
基金This work was supported by grants from the National Natural Science Foundation of China （91019021 and 81430069 to J.C.）, the National Basic Research Program of China （973 Program） （2013CB910902 to J.C.）, Shanghai Committee of Science and Technology （15ZR1424500 to T.W. and 15140904300）, Shanghai Municipal Education Commission （ZZjdyx15003 to T.W. and 2017-01-07-00-01-E00050 to J.C.）, and Shanghai Jiao Tong University School of Medicine （14XJ10001 to T.W.）.
基金the Startup Fund from Shanghai Jiao Tong University (SJTU) School of Medicine, the National Natural Science Foundation of China (31771643)Shanghai Pujiang Program (17PJ1405200)the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, Funding from Shanghai Key Laboratory of Reproductive Medicine to M.Z., and S)TU Researcher program for M.Z. and C.L., respectively.
文摘Transplantation of oligodendrocyte progenitor cells (OPCs) is a promising way for treating demyelinating diseases. However, generation of scalable and autologous sources of OPCs has proven difficult. We previously established a chemical condition M9 that could specifically initiate neural program in mouse embryonic fibroblasts. Here we found that M9 could induce the formation of colonies that undergo mesenchymal-to-epithelial transition at the early stage of reprogramming. These colonies may represent unstable and neural lineage-restricted intermediates that have not established a neural stem cell identity. By modulating the culture signaling recapitulating the principle of OPC development, these intermediate cells could be reprogrammed towards OPC fate. The chemical-induced OPC-like cells (ciOPLCs) resemble primary neural stem cell-derived OPCs in terms of their morphology, gene expression, and the ability of self-renewal. Upon differentiation, ciOPLCs could produce functional oligodendrocytes and myelinate the neuron axons in vitro, validating their OPC identity molecularly and functionally. Therefore, our study provides a non-integrating approach to OPC reprogramming that may ultimately provide an avenue to patient-specific cell-based or in situ regenerative therapy.
基金This work was supported by grants from the National Natural Science Foundation of China(31991194 and 31330046)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19000000)Shanghai Science and Technology Committee(18JC1420301).
文摘Microtubules (MTs) are regulated by a number of known posttranslational modifications (PTMs) on α/β-tubulin to fulfill diverse cellular functions. Here, we showed that SUMOylation is a novel PTM on α-tubulin in vivo and in vitro. The SUMOylation on α-tubulin mainly occurred at Lys 96 (K96), K166, and K304 of soluble α-tubulin and could be removed by small ubiquitin-related modifier (SUMO)-specific peptidase 1. In vitro experiments showed that tubulin SUMOylation could reduce interprotofilament interaction, promote MT catastrophe, and impede MT polymerization. In cells, mutation of the SUMOylation sites on α-tubulin reduced catastrophe frequency and increased the proportion of polymerized α-tubulin, while upregulation of SUMOylation with fusion of SUMO1 reduced α-tubulin assembly into MTs. Additionally, overexpression of SUMOylation-deficient α-tubulin attenuated the neurite extension in Neuro-2a cells. Thus, SUMOylation on α-tubulin represents a new player in the regulation of MT properties.
基金This work was supported by National Natural Science Foundation of China(grant numbers 82073111 and 81874197)to L.H.and Chinese Universities Scientific FundCAMS Innovation Fund for Medical Sciences(2019-I2M-5-051)to G.C.
文摘Dear Editor,Mucin 1(MUC1)contains N-and C-subunit that forms a heterodimer on the apical surface of luminal epithelial cells.Nevertheless,MUC1 is aberrantly overexpressed in various cancers,such as breast cancer,lung cancer,and prostatic cancer,which critically contributes to tumorigenesis and poor clinical outcomes.1 Several strategies have been developed for targeted-inhibition of MUC1 including vaccines,monoclonal antibodies(MAb),and polypeptide.
