Autophagy Regulates Homeostasis of Pluripotency‐Associated Proteins in hESCs

The pluripotency of embryonic stem cells (ESCs) is maintained by intracellular networks of many pluripotency‐associated (PA) proteins such as OCT4, SOX2, and NANOG. However, the mechanisms underlying the regulation of protein homeostasis for pluripotency remain elusive. Here, we first demonstrate th...

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Published inStem cells (Dayton, Ohio) Vol. 32; no. 2; pp. 424 - 435
Main Authors Cho, Yun‐Hee, Han, Kyu‐Min, Kim, Dongkyu, Lee, Joonsun, Lee, Sang‐Hee, Choi, Kyeng‐Won, Kim, Jungho, Han, Yong‐Mahn
Format Journal Article
LanguageEnglish
Published United States Oxford University Press 01.02.2014
Subjects
Autophagy
Autophagy - genetics
Cell culture
Cell Line
Cell signaling
Embryo cells
Embryonic stem cells
Embryonic Stem Cells - metabolism
Homeodomain Proteins - metabolism
Homeostasis
Humans
Nanog Homeobox Protein
Octamer Transcription Factor-3 - metabolism
Pluripotency
Pluripotent Stem Cells - metabolism
Proteasome Endopeptidase Complex - metabolism
Proteins
SOXB1 Transcription Factors - metabolism
Stem cells
Ubiquitin - genetics
Cell culture
Embryonic stem cells
Cell signaling
Pluripotency
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Summary:The pluripotency of embryonic stem cells (ESCs) is maintained by intracellular networks of many pluripotency‐associated (PA) proteins such as OCT4, SOX2, and NANOG. However, the mechanisms underlying the regulation of protein homeostasis for pluripotency remain elusive. Here, we first demonstrate that autophagy acts together with the ubiquitin‐proteasome system (UPS) to modulate the levels of PA proteins in human ESCs (hESCs). Autophagy inhibition impaired the pluripotency despite increment of PA proteins in hESCs. Immunogold‐electron microscopy confirmed localization of OCT4 molecules within autophagosomes. Also, knockdown of LC3 expression led to accumulation of PA proteins and reduction of pluripotency in hESCs. Interestingly, autophagy and the UPS showed differential kinetics in the degradation of PA proteins. Autophagy inhibition caused enhanced accumulation of both cytoplasmic and nuclear PA proteins, whereas the UPS inhibition led to preferentially degrade nuclear PA proteins. Our findings suggest that autophagy modulates homeostasis of PA proteins, providing a new insight in the regulation of pluripotency in hESCs. Stem Cells 2014;32:424–435
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ISSN:1066-5099
1549-4918
DOI:10.1002/stem.1589