Autophagy is required for self-renewal and differentiation of adult human stem cells

Salemi, Souzan; Yousefi, Shída; Constantinescu, Mihai A.; Fey, Martin F.; Simon, Hans‐Uwe

doi:10.1038/cr.2011.200

Cited by 164 publications

(156 citation statements)

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“…In the process of this adaptation to environmental changes, the homeostasis of cellular components such as organelles and proteins is modulated by elaborate cascades of synthesis and catabolism. Recently, it is suggested that higher activity of autophagy is required for maintenance of adult stem cells such hematopoietic stem cells, epidermal stem cells, and dermal stem cells [29][30][31]. Also, it has been reported that Oct4 molecules are degraded by the UPS in ESCs [14][15][16].…”

Section: Discussionmentioning

confidence: 99%

“…Two hESC lines (CHA15-hESC [23], passages 55-85, and H9, passages 50-80) and a human induced pluripotent stem cell (iPSC) line [24] (passages [25][26][27][28][29][30][31][32][33][34][35] were used in this study. They were maintained on Mitomycin C (Sigma-Aldrich, St. Louis, MO, http://www.sigmaaldrich.com)-treated mouse embryonic fibroblasts (mct-MEFs) in the ESC medium at 37 C and 5% CO 2 in air.…”

Section: Chemical Treatments In Hescsmentioning

confidence: 99%

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Autophagy Regulates Homeostasis of Pluripotency-Associated Proteins in hESCs

Cho¹,

Han²,

Kim³

et al. 2014

Stem Cells

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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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Section: Discussionmentioning

confidence: 99%

Section: Chemical Treatments In Hescsmentioning

confidence: 99%

Autophagy Regulates Homeostasis of Pluripotency-Associated Proteins in hESCs

Cho¹,

Han²,

Kim³

et al. 2014

Stem Cells

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“…Whether adult somatic stem cells also have an enhanced proteasome activity remains to be elucidated, but the maintenance of this activity may impact organismal ageing. Experiments with adult somatic stem cells cultured in vitro such as human mesenchymal stem cells (hMSCs) 78 , haematopoietic stem cells (HSCs), dermal stem cells and epidermal stem cells 79 suggest that autophagy activity is increased in these cells compared with their differentiated counterparts. In fetal and postnatal HSCs, a deficiency in essential autophagy genes such as Atg7 or FIP200 deregulates proliferation, suggesting that autophagy is required for stemness of HSCs 80 .…”

Section: Loss Of Clearance Mechanisms As a Determinant Of Ageingmentioning

confidence: 99%

The role of protein clearance mechanisms in organismal ageing and age-related diseases

2014

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“…For example, a study demonstrated that autophagy is highly activated in HSCs in humans and that this process is required for the self-renewal and differentiation of HSCs. 40 Inhibition of autophagy by 3-methyladenine or by Atg5 siRNAmediated knockdown results in a complete blockade of the differentiation and self-renewal of HSCs. 40 Inhibition of autophagy in HSCs by conditional ablation of Atg7 impairs the production of lymphoid and myeloid progenitors, thus suggesting that Atg7 is essential for HSC maintenance in a cell-autonomous fashion ( Table 1).…”

Section: Role Of Autophagy In Hematopoietic Stem Cell Maintenancementioning

confidence: 99%