Harnessing Autophagic Network Is Essential for Trophoblast Stem Cell Differentiation
| Autor: | Rupasri Ain, Safirul Islam, Shreya Das, Rumela Bose, Shreeta Chakraborty |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Autophagosome Cellular differentiation Autophagosome maturation Cell Biology Stem cell marker Vacuolar Sorting Protein VPS15 Mice 03 medical and health sciences 0302 clinical medicine Sequestosome-1 Protein Autophagy medicine Animals Cells Cultured Trophoblast Cell Differentiation Mouse Embryonic Stem Cells Cell Biology Hematology Class III Phosphatidylinositol 3-Kinases Trophoblasts Cell biology DNA-Binding Proteins 030104 developmental biology medicine.anatomical_structure Giant cell embryonic structures Beclin-1 Female Microtubule-Associated Proteins 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Stem Cells and Development. 29:682-694 |
| ISSN: | 1557-8534 1547-3287 |
| DOI: | 10.1089/scd.2019.0296 |
| Popis: | Differentiation of trophoblast stem (TS) cells into various cell lineages of the placenta during mammalian development is accompanied by dynamic changes in its proteome for exerting the highly specialized functions of various cell subtypes. In the present study, we demonstrate that the autophagic machinery, which includes proteins for initiation, vesicle nucleation, and autophagosome maturation are robustly upregulated during differentiation of TS cells. Interestingly, basal levels of autophagy were detectable in the developing mouse placenta as well as TS cells. However, autophagic flux was actively triggered by induction of differentiation evident from LC3 maturation. Formation of Beclin1, Vps34, and PIK3R4 ternary complex at the phagophore assembly site that is typically known to induce autophagy was also enhanced during differentiation. Degradation of the p62/SQSTM1 cargo protein and its colocalization with LC3, a mature autophagosome marker, was most prevalent in the trophoblast giant cells (TGCs) and negligible in other trophoblast cells at day 6 of differentiation. Furthermore, disruption of autophagy by impairing lysosomal fusion in TS cells before induction of differentiation led to a decrease in the giant cell and spongiotrophoblast cell markers Prl3d1, Prl2c2, Prl4a1, and Tpbpα upon differentiation. In addition, inhibition of autophagy was associated with a decrease in nuclear size of TGCs. Taken together, these data highlight that autophagy is a necessary prelude in commitment of trophoblast differentiation from the multipotent TS cells probably by regulating protein turnover at the onset of differentiation. |
| Databáze: | OpenAIRE |
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