Fig. 6: TANGO6-RPB2 axis is critical for mice HSCs expansion in vivo.
From: TANGO6 regulates cell proliferation via COPI vesicle-mediated RPB2 nuclear entry
The immunofluorescent staining images of TANGO6 and COPA in human cord blood stem cells (CBSC) (a) and mice bone marrow cells (BM) (b). The white arrowheads indicate co-localized signals. E, Embryonic. cKO, conditional knock out. Scale bar, 20 μm (a), 10 μm (b). c Photographic images of WT and cKO embryos at E15.5. Scale bar, 20 mm. d WISH of Tango6 in E12.5-E16.5 fetal livers. Scale bar, 20 μm. e Appearance of the E15.5 fetal livers. Scale bar, 2 mm. f Representative FACS profiles of the frequency of LSK (Lin-sca-1+c-kit+) cells in the fetal livers. g The frequency of LSK cells within total fetal liver cells at E15.5. h Representative FACS profiles of the frequency of SLAM-HSC within fetal liver cells. i The statistical graph of proportion of SLAM-HSC cells in E15.5 fetal livers. n = 3 mice in each group). j qRT-PCR result in the LSK cells from E15.5 fetal livers. n = 3. Each dot represents an independent experiment. k The immunofluorescent staining images of Runx1 and RPB2. Scale bar, 10 μm. l Cell-cycle analysis of E15.5 WT and cKO in the LSK cells. m The statistical graph of the cell-cycle distributions in LSK cells. n = 3 mice in each group. The immunofluorescent staining images of Runx1 in WT and cOV (conditional overexpression) mice (n) and corresponding statistical graph (o). (n = 7 visual field in each group). Each point in o denotes the number of Runx1+ cells in a visual field. Scale bar, 20 μm. p Our working model. TANGO6 and RPB2 distribution during various interphases of cell cycle and their interaction mainly occurs at G1/S phase to assure RPB2 nuclear import (left). TANGO6 is anchored to COPI vesicle (purple) via its TM domains (blue). And its N- and C- fragments expose to the cell cytoplasm to capture RPB2 (dark red). TANGO6 carries RPB2 to the nucleus via assistance of ER and KPNB1 (gray) (right). TANGO6-RPB2 axis is functionally conserved in controlling tumor cells and mice HSCs expansion. The models were created with BioRender.com. Source data are provided as a Source Data file.
