Harnessing Autophagic Network Is Essential for Trophoblast Stem Cell Differentiation.

Stem Cells and Development
Shreeta ChakrabortyRupasri Ain

Abstract

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 spo...Continue Reading

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Citations

Sep 11, 2020·Life Science Alliance·Sarbani Saha, Rupasri Ain
Nov 3, 2020·Frontiers in Immunology·Zhaohe LiXin Wang

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Methods Mentioned

BETA
lipidation
Protein Assay
electrophoresis
PCR
Immunoprecipitation
co-immunoprecipitation assay

Software Mentioned

LAS
NIH ImageJ
Leica

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