The Role of Spectrosome and Centrosome in Asymmetric Stem Cell Division
thesisposted on 21.10.2015, 00:00 by Chi Bang
Stem cells have remarkable self-renewal ability and differentiation potency, which are critical for tissue repair and tissue homeostasis. Recently it has been found, in many systems (e.g. gut, neurons, and hematopoietic stem cells), that the self-renewal and differentiation balance is maintained when the stem cells divide asymmetrically—one daughter cell that is displaced outside of the stem cell ‘niche’ due to polarity orientation is differentiated while the other daughter cell that is positioned inside of the ‘niche’ is self-renewed. However, how the self-renewal and differentiation is balanced to maintain the tissue homeostasis is poorly understood. Using the Germline Stem Cells (GSCs) of Drosophila male gonad, time-lapse live-cell imaging microscopy, and our customized tracking programs, the movement patterns of spectrosomes (GSC organelle previously shown to regulate spindle orientation) and centrosomes were tracked to quantify the dynamic characteristics, which included velocities, migration distances, spindle angle changes, spindle separation velocities, and angular spindle velocities. These studies provided greater insights of how the asymmetric stem cell division is regulated. Our investigation focuses were twofold: 1) to elucidate how centrosome and spectrosome interact to regulate the asymmetric stem cell division outcome and 2) how pericentriolar matrix (PCM; matrix that envelopes centrosome)/astral microtubules and Adenomatous Polyposis Coli 2 (APC2; adhesion protein) participate in the regulation of asymmetric stem cell divisions in conjunction with spectrosome and non-functional centrosomes. With centrosome compromised through a core protein knockout in the male GSCs, the spectrosome changed localization (to apical position shown to be important in anchoring the mitotic spindle pole in the female GSCs for controlling the spindle orientation) and became stationary. Furthermore, the spectrosomes were also apically positioned when the centrosomes and spindles were misoriented. In addition, the spectrosomes were recruited to the apical position when the PCM/astral microtubules were compromised (via cnn mutation) but not APC2. Our results suggest that spectrosome is recruited to the apical cortex to orient the spindle when PCM/astral microtubules are compromised but not APC2. Our dissertation results can be used as a model to control the fate of other stem cell types and spill into potential applications and therapies.