TY - JOUR
T1 - CXCR2 Ligands and mTOR Activation Enhance Reprogramming of Human Somatic Cells to Pluripotent Stem Cells
AU - Lee, Seung Jin
AU - Kang, Ka Won
AU - Kim, Ji Hea
AU - Lee, Byung Hyun
AU - Jung, Ji Hye
AU - Park, Yong
AU - Hong, Soon Cheol
AU - Kim, Byung Soo
N1 - Funding Information:
This work was supported, in part, by Brain Korea 21 Plus Grant Program from the Ministry of Education, Republic of Korea.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Induced pluripotent stem cell (iPSC) technology has great promise in regenerative medicine and disease modeling. In this study, we show that human placenta-derived cell conditioned medium stimulates chemokine (C-X-C motif) receptor 2 (CXCR2) in human somatic cells ectopically expressing the pluripotency-associated transcription factors Oct4, Sox2, Klf4, and cMyc (OSKM), leading to mechanistic target of rapamycin (mTOR) activation. This causes an increase in endogenous cMYC levels and a decrease in autophagy, thereby enhancing the reprogramming efficiency of human somatic cells into iPSCs. These findings were reproduced when human somatic cells after OSKM transduction were cultured in a widely used reprogramming medium (mTeSR) supplemented with CXCR2 ligands interleukin-8 and growth-related oncogene α or an mTOR activator (MHY1485). To our knowledge, this is the first report demonstrating that mTOR activation in human somatic cells with ectopic OSKM expression significantly enhances the production of iPSCs. Our results support the development of convenient protocols for iPSC generation and further our understanding of somatic cell reprogramming.
AB - Induced pluripotent stem cell (iPSC) technology has great promise in regenerative medicine and disease modeling. In this study, we show that human placenta-derived cell conditioned medium stimulates chemokine (C-X-C motif) receptor 2 (CXCR2) in human somatic cells ectopically expressing the pluripotency-associated transcription factors Oct4, Sox2, Klf4, and cMyc (OSKM), leading to mechanistic target of rapamycin (mTOR) activation. This causes an increase in endogenous cMYC levels and a decrease in autophagy, thereby enhancing the reprogramming efficiency of human somatic cells into iPSCs. These findings were reproduced when human somatic cells after OSKM transduction were cultured in a widely used reprogramming medium (mTeSR) supplemented with CXCR2 ligands interleukin-8 and growth-related oncogene α or an mTOR activator (MHY1485). To our knowledge, this is the first report demonstrating that mTOR activation in human somatic cells with ectopic OSKM expression significantly enhances the production of iPSCs. Our results support the development of convenient protocols for iPSC generation and further our understanding of somatic cell reprogramming.
KW - CXCR2 ligands
KW - induced pluripotent stem cells
KW - mTOR activator
KW - pluripotency signaling pathway
KW - reprogramming efficiency
UR - http://www.scopus.com/inward/record.url?scp=85078870537&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85078870537&partnerID=8YFLogxK
U2 - 10.1089/scd.2019.0188
DO - 10.1089/scd.2019.0188
M3 - Article
C2 - 31808362
AN - SCOPUS:85078870537
VL - 29
SP - 119
EP - 132
JO - Stem Cells and Development
JF - Stem Cells and Development
SN - 1547-3287
IS - 3
ER -
