Early Committed Clockwise Cell Chirality Upregulates Adipogenic Differentiation of Mesenchymal Stem Cells

Abstract

Cell chirality is observed with diverse forms and coordinates various left-right (LR) asymmetry in tissue morphogenesis. To give rise to such diversity, cell chirality may be coupled with cell differentiation. Here, using micropatterned human mesenchymal stem cells (hMSCs), an early committed clockwise (CW) cell chirality that can itself upregulate the adipogenic differentiation is reported. hMSC chirality enables a positively tilted chiral orientation on micropatterned stripes. When cultured as single cells on circular micropatterns, an anticlockwise (ACW)-biased nucleus rotation and swirling pattern of actin filament are observed. Interestingly, with adipogenic induction for 3-6 days, such chirality is reversed to negative chiral orientation and CW-biased rotation, which is earlier than the maturation of other differentiation markers, and consistently expressed in terminally differentiated adipocytes. Using latrunculin A (LatA), cytochalasin D (CD), and nocodazole (Noco) that forces a CW-biased actin filament and nucleus rotation resembling the early differentiated chirality upon adipogenic induction, an upregulation of adipogenic differentiation is found. The result demonstrates that the early differentiated chirality may serve as a mechanical precursor to engage the lineage commitment, suggesting a feedback mechanism of chiral actin in regulating cell differentiation and LR morphogenesis.