title: Oxygen tension regulates NK cells differentiation from hematopoietic stem cells in vitro.
abstract: Natural killer (NK) cells are differentiated from hematopoietic stem cells (HSCs) which are located at the lowest end of an oxygen gradient within the bone marrow (BM). In this report, we investigated whether oxygen tension could affect NK cell differentiation from hematopoietic cells in vitro. We found that hypoxia led to an inhibition of differentiation in NK cells, and increased oxygen supply alleviated this inhibition and restored NK cell differentiation under hypoxic condition. Hypoxia-treated cells demonstrated reduced mRNA expression of transcription factors (TFs) that have important roles in NK cell differentiation, such as EOMES, T-bet, GATA-3 and ETS-1. Moreover, hypoxia-pretreated cells recovered mRNA expression of TFs when the oxygen tension was changed to normoxia. Our findings suggest that oxygen tension modulates in vitro differentiation of NK cells through the regulation of TF expression.
authors.affiliation: Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Republic of Korea.
authors.forename: Sohyun
authors.initials: S
authors.lastname: Yun
authors.forename: Suk Hyung
authors.initials: SH
authors.lastname: Lee
authors.forename: Suk-Ran
authors.initials: SR
authors.lastname: Yoon
authors.forename: Pyung-Keun
authors.initials: PK
authors.lastname: Myung
authors.forename: Inpyo
authors.initials: I
authors.lastname: Choi
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D010100:Oxygen / Q000008:administration & dosage* / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D000098815:T-bet Transcription Factor
chemical_list: C491199:EOMES protein, human; C494041:ETS1 protein, human; D050990:GATA3 Transcription Factor; D050784:Proto-Oncogene Protein c-ets-1; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D010100:Oxygen