Research

Multipotent intestinal stem cells maintain the homeostasis and function of Drosophila intestinal epithelium

A model of Drosophila multipotent intestinal stem cells that use Notch signalling to generate daughter cells with different fates at different times and in different places. 

When Drosophila intestinal stem cells divide at the adult stage, 90% of the divisions are to give rise to EB cells, which will differentiate into intestinal epithelial cells in the future. At this time, the stem cells strongly activate the Notch signaling pathway in the EB and induce the EB to differentiate into epithelial cells (ECs). After a certain number of divisions, the stem cells accumulate a sufficient amount of Sc protein and begin to express the endocrine cell differentiation factor Pros. After asymmetric division, the stem cells divide to produce endocrine precursor cells (EEP/EMC). At this point, EMC expresses a ligand for the Notch signalling pathway, weakly activates the Notch signalling pathway in stem cells, inhibits the expression of Sc, maintains stem cell stemness and then divides into a pair of endocrine cells. Since the stem cells no longer express Sc, they become intestinal stem cells that produce EC, and their fate continues to oscillate between ① and ②. ③ When Notch signaling is additionally activated in stem cells and progeny cells, the stem cells differentiate into EC cells. When the Notch signaling pathway is mutated in stem cells and progeny cells, ISC-like or ee-like intestinal tumours are formed.

Drosophila intestinal stem cell is an ideal model for studying the number and location of stem cells

Changes in the number and division pattern of Drosophila intestinal stem cells in the pupal stage.

Left: Model of the number and distribution pattern of stem cells and endocrine cells in the intestine; Right: Model of the division pattern of intestinal stem cells in the pupal stage. A: At 44h APF, the number of stem cells in the intestine is about 600. At this time, the stem cells express the cell polarity protein Mira and the endocrine cell differentiation transcription factor Pros. Under the influence of Mira, Pros accumulates on the cell membrane at the basal side of the stem cells. B: When stem cells divide asymmetrically into two, about 600 stem cells and 600 endocrine cells are distributed in the intestine. At 56h APF, stem cells and endocrine cells each divide symmetrically. Pros is in the cytoplasm during symmetric division. C: Symmetric division makes the number of stem cells and endocrine cells in the intestine reach about 1200 at 72h APF. Pros protein is located in the nucleus of endocrine cells.

Similarities and differences between asymmetric division of Drosophila neural stem cells and intestinal stem cells

The pattern and molecular mechanism of asymmetric division of Drosophila type 1 neural stem cells and intestinal stem cells.

A: Drosophila type 1 neural stem cells undergo asymmetric division during the embryonic stage. The division axis is perpendicular to the "apical-basal" axis, giving rise to two progeny cells, one large and one small. The large apical progeny cells continue to occupy the apical position of the neural stem cells in the outermost ectoderm, maintaining stem cell self-renewal. The basal daughter cells differentiate into ganglion cells (GMCs) and then undergo symmetric division to give rise to a pair of nerves. B: The molecular mechanism of asymmetric division of neural stem cells: (1) Par complex localises to the apical cell membrane to establish an internal polarity axis; (2) Par complex localises Pon and Miranda to the basal cell membrane through phosphorylation, Pon and Miranda are further physically combined to localise Numb, Brat and Prospero to the basal cell membrane; (3) the Par complex recruits Inscuteable, Pins, Gαi and Mud to establish an "apical-basal" mitotic spindle axis; (4) the apical polar protein and the basal cell fate determinants are asymmetrically distributed in the two daughter cells. C: In metaphase of asymmetric division of intestinal stem cells, the Par protein complex is located at the apical side of the cell membrane and Miranda and Prospero are located at the basal side of the cell membrane, forming a spindle axis perpendicular to the basal membrane. As mitosis progresses, the spindle axis continuously shifts from perpendicular to the basal membrane until it is parallel to the basal membrane at the end of mitosis. After the separation of the mitotic cytoplasm, the progeny cells, originally located at the apical end of metaphase, return to the basal membrane and become stem cells that continue to renew themselves. The Prospero protein enters the nucleus of the progeny cells, which are originally basal cells, and allows the progeny cells to differentiate into endocrine cells.