CXCR2 Ligands and mTOR Activation Enhance Reprogramming of Human Somatic Cells to Pluripotent Stem Cells

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 pluripot...

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Vydáno v:Stem cells and development Ročník 29; číslo 3; s. 119
Hlavní autoři: Lee, Seung-Jin, Kang, Ka-Won, Kim, Ji-Hea, Lee, Byung-Hyun, Jung, Ji-Hye, Park, Yong, Hong, Soon-Cheol, Kim, Byung-Soo
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.02.2020
Témata:
Cells, Cultured
Cellular Reprogramming
Cellular Reprogramming Techniques - methods
Chemokine CXCL1 - pharmacology
Culture Media, Conditioned - pharmacology
Female
Fibroblasts - cytology
Fibroblasts - drug effects
Fibroblasts - metabolism
Human Umbilical Vein Endothelial Cells - cytology
Human Umbilical Vein Endothelial Cells - drug effects
Human Umbilical Vein Endothelial Cells - metabolism
Humans
Induced Pluripotent Stem Cells - cytology
Induced Pluripotent Stem Cells - metabolism
Interleukin-8 - pharmacology
Kruppel-Like Transcription Factors - genetics
Kruppel-Like Transcription Factors - metabolism
Morpholines - pharmacology
Octamer Transcription Factor-3 - genetics
Octamer Transcription Factor-3 - metabolism
Proto-Oncogene Proteins c-myc - genetics
Proto-Oncogene Proteins c-myc - metabolism
Receptors, Interleukin-8B - metabolism
SOXB1 Transcription Factors - genetics
SOXB1 Transcription Factors - metabolism
TOR Serine-Threonine Kinases - metabolism
Triazines - pharmacology
CXCR2 ligands
mTOR activator
induced pluripotent stem cells
reprogramming efficiency
pluripotency signaling pathway
ISSN:1557-8534, 1557-8534
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Popis
Shrnutí: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 , , , and (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.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1557-8534
1557-8534
DOI:10.1089/scd.2019.0188