Homing and engraftment of human hematopoietic stem/progenitor cells are regulated by R4 RGS family proteins
Refereed conference paper presented and published in conference proceedings


其它資訊
摘要Background and Aims
The homing and engraftment efficiency of haematopoietic stem/progenitor cells (HSC, marked by CD34 antigen in human) is an important determinant of successful clinical stem cell transplantation, but the mechanism regulating these processes remains insufficiently understood. Here, we characterised the expression pattern of R4 RGS proteins in human CD34+ cells and studied their functional roles in HSC homing and engraftment.
Methods
The mRNA expressions of R4 RGS family members in various sources of CD34+ cells were analysed by qRT-PCR. Homing-related functions of RGS proteins were tested in a series of in vitro assays. The NOD/SCID mouse model was used to study the role of RGS proteins in homing and engraftment of CD34+ cells in vivo.
Results
Our results showed that CD34+ HSC derived from cord blood (CB) expressed RGS1-3, 5, 13, 16 and 18 at mRNA level, whereas expressions of RGS4, 8 and 21 were undetectable. Exposure of CB CD34+ cells to the homing cytokine SDF-1 significantly increased RGS1, 2, 13 and 16 expressions and decreased RGS3 and 18 expressions. Consistently, expressions of RGS1, 13 and 16 were significantly higher in bone marrow (BM) CD34+ cells when compared to mobilised peripheral blood (MPB) CD34+ cells, while RGS3 and 18 expressions were lower in BM CD34+ cells, suggesting a SDF-1- and niche-dependent regulation of RGS expressions. We also showed that lentivirus-mediated overexpression of RGS1, 13 and 16 but not RGS2 significantly inhibited migration of CD34+ cells to a SDF-1 gradient. Similarly, RGS1, 13 and 16 overexpression suppressed SDF-1-induced Akt phosphorylation, but none of them affected SDF-1-mediated actin polymerisation. In the NOD/SCID mouse model, both short-term homing and long-term engraftment were impaired in RGS1-, RGS13- and RGS16-overexpressing CD34+ cells.
Conclusions
This study provided the first evidence that expressions of R4 RGS proteins are regulated by the SDF-1/CXCR4 axis in CD34+ HSC. We also presented evidence that specific R4 RGS proteins negatively regulate in vitro SDF-1-mediated responses and in vivo HSC homing/engraftment. Strategies to inhibit RGS signaling could thus be a potential method for enhancing HSC homing and engraftment efficiency, which is particularly important in the setting of CB transplantation.
著者Wong YT, Li CK, Chan KY, Ng PC, Li K, Leung TF, Leung KT
會議名稱4th Annual Meeting of the Hong Kong College of Paediatricians
會議開始日03.12.2016
會議完結日04.12.2017
會議地點Hong Kong
會議國家/地區香港
出版年份2016
月份12
語言美式英語

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