Lineage-Specific Sox7 Expression In Hematopoietic Progenitor Cells Derived From Human Umbilical Cord Blood

The SOX (Sry-related HMG box) genes belong to a family of transcription factors containing a High-Mobility-Group box domain. In an initial screen of SOX genes in human leukemias, SOX7 is uniquely down-regulated in acute myeloid leukemia, myelodysplastic syndrome and chronic myelogenous leukemia but up-regulated in most cases of acute lymphoblastic leukemia. The observation led to the proposition that SOX7 may play a role in lineage differentiation in hematopoiesis. In this study, we examined SOX7 expression in human umbilical cord blood (UCB) with a view to understand its role in hematopoietic lineage specification.

Mononuclear cells (MNC) were isolated from UCB and fractionated into CD34⁺, CD34^-, CD34⁺CD38⁺ and CD34⁺CD38^- populations by immunomagnetic selection and fluorescence activated cell sorting (FACS). 0.1–0.4 × 10⁶ CD34⁺ UCB cells were transplanted intravenously into sub-lethally irradiated NOD/SCID mice with or without prior anti-CD122 antibody injection. Donor engraftment was assessed after 7–8 weeks and engrafting human cells were sorted for CD34⁺, CD33⁺, CD19⁺ expression. CD34⁺ UCB cells were also plated in colony-forming unit (CFU) assay. SOX7 expression was evaluated by quantitative real-time reverse-transcriptase polymerase chain reaction (Q-RT-PCR).

The relative SOX7 expression in CD34⁺ and CD34⁺CD38^- UCB cells was 9.15±2.18 and 4.53±1.09 fold higher than in CD34^- (P=0.0001) and CD34⁺CD38⁺ (P=0.014) respectively. SOX7 expression in CD34⁺ cells (arbitrarily set as 1.0) was down-regulated upon differentiation in CFU assay (CFU-GM/G: 0.09±0.06 fold, P=0.007; BFU-E: 0.05±0.03 fold, P=0.003). CD34⁺ cells engrafted into NOD/SCID mice as enumerated by human CD45⁺ cells in mouse BM (with anti-CD122: 51±6.3%; without anti-CD122: 28±9%; p=0.017) and gave rise to predominantly B-lymphoid (CD19⁺) (53.1±8.18%) and to a less extent myeloid (CD33⁺) (2.9±0.54%) differentiated cells. Prior injection with anti-CD122 antibody had no effect on lineage differentiation and the results were pooled. When SOX7 expression in engrafting myeloid and B-lymphoid differentiated cells (arbitrarily set as 1.0) were compared, it was significantly down-regulated in the myeloid series (0.28±0.08 fold, p = 0.036).

SOX7 is selectively expressed in human HSC from UCB. It is preferentially down-regulated during myeloid differentiation both in-vivo and in-vitro. The function of SOX7 during lineage specification and its link to myeloid malignancies is currently investigated in our laboratory.

The project was supported by a grant from the strategic Research Theme of cancer stem cells in the HKU.

No relevant conflicts of interest to declare.