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Autophagy and cell reprogramming

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Abstract

Autophagy is an evolutionarily conserved process that degrades cytoplasmic components, thus contributing to cell survival and tissue homeostasis. Recent studies have demonstrated that autophagy maintains stem cells in relatively undifferentiated states (stemness) and also contributes to differentiation processes. Autophagy likewise plays a crucial role in somatic cell reprogramming, a finely regulated process that resets differentiated cells to a pluripotent state and that requires comprehensive alterations in transcriptional activities and epigenetic signatures. Autophagy assists in manifesting the functional consequences that arise from these alterations by modifying cellular protein expression profiles. The role of autophagy appears to be particularly relevant for early phases of cell reprogramming during the generation of induced pluripotent stems cells (iPSCs). In this review, we provide an overview of the core molecular machinery that constitutes the autophagic degradation system, describe the roles of autophagy in maintenance, self-renewal, and differentiation of stem cells, and discuss the autophagic process and its regulation during cell reprogramming.

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Abbreviations

Ambra1:

Activating molecule in Beclin1-regulated autophagy 1

AMPK:

AMP-activated protein kinase

Atg:

Autophagy-related proteins

Beclin 1:

Coiled-coil, myosin-like BCL2-interacting protein

BafA1:

Bafilomycin A1

CSC:

Cancer stem cell

CHD:

Chromodomain, helicase, DNA binding

EMT:

Epithelial–mesenchymal transition

ESC:

Embryonic stem cell

FGF:

Fibroblast growth factor

GBM:

Glioblastoma

GAP:

GTPase-activating protein

HSC:

Hematopoietic stem cell

iPSC:

Induced pluripotent stem cell

LC3:

Microtubule-associated protein light chain 3

LIF:

Leukemia inhibitory factor

MBD3:

Methyl-CpG binding domain protein 3

mTOR:

Mammalian target of rapamycin

NuRD:

Nucleosome remodeling and deacetylase

NSC:

Neural stem cell

PE:

Phosphatidylethanolamine

Rheb:

Ras homologue enriched in brain

ROS:

Reactive oxygen species

Sox2:

SRY (sex determining region Y)-box 2

SVZ:

Subventricular zone

TSC1/2:

Tuberous sclerosis1/2

ULK:

Unc-51-like kinase

WASH:

Wiskott–Aldrich syndrome protein and SCAR homologue

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (31300645, 81330047), 973 Program of the MOST of China (2010CB911902), and the Strategic Priority Research Programs of the Chinese Academy of Sciences (XDA01010407). MR and ZF are supported by the Science Foundation Ireland International Strategic Collaboration Programme: China (ISCP China).

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Authors and Affiliations

  1. CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

    Shuo Wang, Pengyan Xia & Zusen Fan

  2. Department of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland

    Markus Rehm

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  1. Shuo Wang
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  2. Pengyan Xia
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  4. Zusen Fan
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Correspondence to Zusen Fan.

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Wang, S., Xia, P., Rehm, M. et al. Autophagy and cell reprogramming. Cell. Mol. Life Sci. 72, 1699–1713 (2015). https://doi.org/10.1007/s00018-014-1829-3

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