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. 2018 Mar 20;243(6):563–575. doi: 10.1177/1535370218759636

Table 1.

Summary of the sirtuin family proteins that are involved in stem cell differentiation and iPSC formation.

ActivityReference Localization Reference Reprogramming Reference Pluripotency and stem cell properties Reference Differentiation Reference
SIRT1 Deacetylation14 Nucleus (++++) Cytosol (−/+)5–7

  1. Control of DNA integrity and genome stability15

  2. Telomere elongation36,37

  3. SOX2 deacetylation24

  4. miR-34a–SIRT1–p53 axis28,29

  1. Positive regulation through upregulation of Nanog, Sox2, and Oct428,29

  2. Global DNA repair31,32

  1. Negative regulation on adipogenesis and neurogenesis by FoxO1/PPARα axis19–22

  2. Positive regulation on osteogenesis and myogenesis by Wnt/β-catenin signaling40–45
SIRT2 Deacetylation46,47 Nucleus (−/+)Cytosol (++++)8,9 Metabolic shift by acetylation of glycolytic enzymes, such as GAPDH, PGK1, ENO1, PKM, and ALDOA51 Negative regulation51

  1. Positive regulation on neurogenesis by ERK1/2/CREB signaling51

  2. Negative regulation on adipogenesis by FoxO1/PPARγ axis56,57
SIRT3 Deacetylation62 Nucleus (−/+)Cytosol (−/+)Mitochondria (++++)12,13 Facilitate the reprogramming of somatic cells from old individuals by downregulation of cellular ROS signaling and aging processes62 NA Positive regulation on adipogenesis and osteogenesis by induction of PGC-1α and MnSOD, and FoxO3a signaling60,75
SIRT4 Deacetylation of ADP-ribosyltransferase82 Nucleus (−/+)Cytosol (−/+)Mitochondria (++++)11 Facilitate the reprogramming of somatic cells from old individuals by preventing somatic cell senescence83 NA NA
SIRT5 Deacetylation86,87Desuccinylation85,86,123Demalonylation86 Nucleus (−/+)Cytosol (−/+)Mitochondria (++++)10 NA Negative regulation through LIF/JAK/STAT3 axis88,89 Negative regulation on adipogenesis61
SIRT6 Deacetylation102 Nucleus (++++) Cytosol (−/+)5–7 Facilitate the reprogramming of somatic cells from old individuals by acetylation of Sox2, Oct4, and Nanog100,101 NA Positive regulation on adipogenesis and osteogenesis95–97
SIRT7 Deacetylation Nucleus (++++) Cytosol (−/+)5–7 Promoting the MET process111,112 NA

  1. Positive regulation on adipogenesis106

  2. Negative regulation on osteogenesis107 by suppression of Wnt/β-catenin signaling106

GAPDH: glyceraldehyde 3-phosphate dehydrogenase; PGK1: phosphoglycerate kinase 1; ENO1: enolase 1; PKM: phosphoglycerate mutase M; ALDOA: aldolase A; MET: mesenchymal-to-epithelial transition; NA: not available.

Protein localization: −/+: 0–10%, +: 10–25%, ++: 25–50%, +++: 50–75%, ++++: 75–100%.