摘要
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.
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
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）.
