Leukocyte differentiation antigens （LDAs） play important roles in the immune system, by serving as surface markers and participating in multiple biological activities, such as recognizing pathogens, mediating membra...Leukocyte differentiation antigens （LDAs） play important roles in the immune system, by serving as surface markers and participating in multiple biological activities, such as recognizing pathogens, mediating membrane signals, interacting with other cells or systems, and regulating cell differentiation and activation. Data mining is a powerful tool used to identify novel LDAs from whole genome. LRRC25 （leucine rich repeat-containing 25） was predicted to have a role in the function of myeloid cells by a large-scale ＂omics＂ data analysis. Further experimental validation showed that LRRC25 is highly expressed in primary myeloid cells, such as granulocytes and monocytes, and lowly/intermediately expressed in B cells, but not in T cells and almost all NK cells. It was down-regulated in multiple acute myeloid leukemia （AML） cell lines and bone marrow cells of AML patients and up-regulated after all-trans retinoic acid （ATRA）-mediated granulocytic differentiation in AML cell lines and acute promyelocytic leukemia （APL; AML-M3, FAB classification） cells. Localization analysis showed that LRRC25 is a type I transmembrane molecule. Although ectopic LRRC25 did not promote spontaneous differentiation of NB4 cells, knockdown of LRRC25 by siRNA or shRNA and knockout of LRRC25 by the CRISPR-Cas9 system attenuated ATRA-induced termi- nal granulocytic differentiation, and restoration of LRRC25 in knockout cells could rescue ATRA-induced granulocytic differentiation. Therefore, LRRC25, a potential leukocyte differentiation antigen, is a key regulator of ATRA-induced granulocytic differentiation.展开更多
A single-nucleotide polymorphism(SNP)is an alteration in one nucleotide in a certain position within a genome.SNPs are associated with disease susceptibility.However,the influences of SNPs on the pathogenesis of neona...A single-nucleotide polymorphism(SNP)is an alteration in one nucleotide in a certain position within a genome.SNPs are associated with disease susceptibility.However,the influences of SNPs on the pathogenesis of neonatal hypoxic-ischemic brain damage remain elusive.Seven-day-old rats were used to establish a hypoxic ischemic encephalopathy model.SNPs and expression profiles of mRNAs were analyzed in hypoxic ischemic encephalopathy model rats using RNA sequencing.Genes exhibiting SNPs associated with hypoxic ischemic encephalopathy were identified and studied by gene ontology and pathway analysis to identify their possible involvement in the disease mechanism.We identified 89 up-regulated genes containing SNPs that were mainly located on chromosome 1 and 2.Gene ontology analysis indicated that the up-regulated genes containing SNPs are mainly involved in angiogenesis,wound healing and glutamatergic synapse and biological processing of calcium-activated chloride channels.Signaling pathway analysis indicated that the differentially expressed genes play a role in glutamatergic synapses,long-term depression and oxytocin signaling.Moreover,intersection analysis of high throughput screening following PubMed retrieval and RNA sequencing for SNPs showed that CSRNP1,DUSP5 and LRRC25 were most relevant to hypoxic ischemic encephalopathy.Significant up-regulation of genes was confirmed by quantitative real-time polymerase chain reaction analysis of oxygen-glucose-deprived human fetal cortical neurons.Our results indicate that CSRNP1,DUSP5 and LRRC25,containing SNPs,may be involved in the pathogenesis of hypoxic ischemic encephalopathy.These findings indicate a novel direction for further hypoxic ischemic encephalopathy research.This animal study was approved on February 5,2017 by the Animal Care and Use Committee of Kunming Medical University,Yunnan Province,China(approval No.kmmu2019038).Cerebral tissue collection from a human fetus was approved on September 30,2015 by the Ethics Committee of Kunming Medical University,China(approval No.2015-9).展开更多
基金We appreciate the assistance and advice from Professor Dalong Ma from the Department of Immunology, Peking University Health Science Center and thank Hounan Wu, a technician in the Analytic Center of Peking University Health Science Center, for her professional and skilled help in micro-well single cell sorting. This work was supported by the National Natural Science Foundation of China （Grant Nos. 31400736 and 31670947）.
文摘Leukocyte differentiation antigens （LDAs） play important roles in the immune system, by serving as surface markers and participating in multiple biological activities, such as recognizing pathogens, mediating membrane signals, interacting with other cells or systems, and regulating cell differentiation and activation. Data mining is a powerful tool used to identify novel LDAs from whole genome. LRRC25 （leucine rich repeat-containing 25） was predicted to have a role in the function of myeloid cells by a large-scale ＂omics＂ data analysis. Further experimental validation showed that LRRC25 is highly expressed in primary myeloid cells, such as granulocytes and monocytes, and lowly/intermediately expressed in B cells, but not in T cells and almost all NK cells. It was down-regulated in multiple acute myeloid leukemia （AML） cell lines and bone marrow cells of AML patients and up-regulated after all-trans retinoic acid （ATRA）-mediated granulocytic differentiation in AML cell lines and acute promyelocytic leukemia （APL; AML-M3, FAB classification） cells. Localization analysis showed that LRRC25 is a type I transmembrane molecule. Although ectopic LRRC25 did not promote spontaneous differentiation of NB4 cells, knockdown of LRRC25 by siRNA or shRNA and knockout of LRRC25 by the CRISPR-Cas9 system attenuated ATRA-induced termi- nal granulocytic differentiation, and restoration of LRRC25 in knockout cells could rescue ATRA-induced granulocytic differentiation. Therefore, LRRC25, a potential leukocyte differentiation antigen, is a key regulator of ATRA-induced granulocytic differentiation.
基金supported by the program Innovative Research Team in Science and Technology in Yunnan Province of China(to THW)the National Natural Science Foundation of China,No.81601074Sichuan Provincial Scientific Foundation Grant of China,No.2017SZ0145
文摘A single-nucleotide polymorphism(SNP)is an alteration in one nucleotide in a certain position within a genome.SNPs are associated with disease susceptibility.However,the influences of SNPs on the pathogenesis of neonatal hypoxic-ischemic brain damage remain elusive.Seven-day-old rats were used to establish a hypoxic ischemic encephalopathy model.SNPs and expression profiles of mRNAs were analyzed in hypoxic ischemic encephalopathy model rats using RNA sequencing.Genes exhibiting SNPs associated with hypoxic ischemic encephalopathy were identified and studied by gene ontology and pathway analysis to identify their possible involvement in the disease mechanism.We identified 89 up-regulated genes containing SNPs that were mainly located on chromosome 1 and 2.Gene ontology analysis indicated that the up-regulated genes containing SNPs are mainly involved in angiogenesis,wound healing and glutamatergic synapse and biological processing of calcium-activated chloride channels.Signaling pathway analysis indicated that the differentially expressed genes play a role in glutamatergic synapses,long-term depression and oxytocin signaling.Moreover,intersection analysis of high throughput screening following PubMed retrieval and RNA sequencing for SNPs showed that CSRNP1,DUSP5 and LRRC25 were most relevant to hypoxic ischemic encephalopathy.Significant up-regulation of genes was confirmed by quantitative real-time polymerase chain reaction analysis of oxygen-glucose-deprived human fetal cortical neurons.Our results indicate that CSRNP1,DUSP5 and LRRC25,containing SNPs,may be involved in the pathogenesis of hypoxic ischemic encephalopathy.These findings indicate a novel direction for further hypoxic ischemic encephalopathy research.This animal study was approved on February 5,2017 by the Animal Care and Use Committee of Kunming Medical University,Yunnan Province,China(approval No.kmmu2019038).Cerebral tissue collection from a human fetus was approved on September 30,2015 by the Ethics Committee of Kunming Medical University,China(approval No.2015-9).
