Abstract
Differentiation of stem/progenitor cells is associated with a substantial increase in mitochondrial mass and complexity. Mitochondrial dynamics, including the processes of fusion and fission, plays an important role for somatic cell reprogramming and pluripotency maintenance in induced pluripotent cells (iPSCs). However, the role of mitochondrial dynamics during stem/progenitor cell differentiation in vivo remains elusive. Here we found differentiation of Drosophila intestinal stem cell is accompanied with continuous mitochondrial fusion. Mitochondrial fusion defective(opa1RNAi) ISCs contain less mitochondrial membrane potential, reduced ATP, and increased ROS level. Surprisingly, suppressing fusion also resulted in the failure of progenitor cells to differentiate. Cells did not switch on the expression of differentiation markers, and instead continued to show characteristics of progenitor cells. Meanwhile, proliferation or apoptosis was unaffected. The differentiation defect could be rescued by concomitant inhibition of Drp1, a mitochondrial fission molecule. Moreover, ROS scavenger also partially rescues opa1RNAi-associated differentiation defects via down-regulating JNK activity. We propose that mitochondrial fusion plays a pivotal role in controlling the developmental switch of stem cell fate.
Highlights
Stem differentiation is accompanied by pronounced changes in mitochondria
The adult progenitor/stem cells in the hindgut proliferation zone (HPZ) domain located adjacent to the malpighian tubes and the mitochondria in these cells are small and round in shape and cristae is rarely observed (Fig. 1c)
Pdm-1, a Discussion Our results here indicated that mitochondrial fusion, followed by increased functional output, forms part of the causal chain that switches the cells state from stem/progenitor cell towards differentiation
Summary
Stem differentiation is accompanied by pronounced changes in mitochondria. Mitochondria increase dramatically in mass and form an extensive tubular network[1,2,3,4,5], while somatic cell reprogramming is accompanied by depletion of mitochondria through mitophagy (mitochondrial autophagy)[6]. In E13.5 hearts the mitochondrial mass increases substantially, accompanied by maturation of the organelle as indicated by abundant laminar cristae[7,8]. One of the major obstacles for somatic reprogramming induced cardiomyocytes is to obtain functional mitochondria[8]. How these mitochondrial changes are regulated remains unexplored in vivo
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