GSE116708
Aging alters the epigenetic asymmetry of HSC division [scRNA-Seq]
Hematopoietic stem cells (HSCs) balance self-renewal and differentiation to maintain homeostasis. With aging, the  frequency of polar HSCs decreases. Cell polarity in HSCs is controlled by the activity of the small RhoGTPase Cdc42. Here  we demonstrate, using a comprehensive set of paired daughter cell analyses that include single cell 3D-confocal imaging,  single cell transplants, single cell RNA-seq as well as single cell ATAC-seq, that the outcome of HSC divisions is strongly  linked to the polarity status before mitosis, which is in turn determined by the level of the activity Cdc42 in stem cells.  Aged apolar HSCs undergo preferentially self-renewing symmetric divisions, resulting in daughter stem cells with  reduced regenerative capacity and lymphoid potential, while young polar HSCs undergo preferentially asymmetric  divisions. Mathematical modeling in combination with experimental data implies a mechanistic role of the asymmetric  sorting of Cdc42 in determining the potential of daughter cells via epigenetic mechanisms. Therefore, molecules that  control HSC polarity might serve as modulators of the mode of stem cell division regulating the potential of daughter  cells. Overall design: Sorted single cells were cultured with and without treatment in the presence of cytokines until first cell division (40-44hrs). The daughter cells were manually separated, washed with PBS and collected for RNA sequencing.