A Novel Small Molecule Facilitates the Reprogramming of Human Somatic Cells into a Pluripotent State and Supports the Maintenance of an Undifferentiated State of Human Pluripotent Stem Cells

Lee, Jungwoon; Xia, Yan; Son, Mi‐Young; Jin, Guang‐Zhen; Seol, Binna; Kim, Minjeong; Son, Myung Jin; Do, Misol; Kim, Dongsup; Lee, Kyeong; Cho, Yee Sook

doi:10.1002/anie.201206691

Cited by 42 publications

(30 citation statements)

References 31 publications

(19 reference statements)

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“…Therefore, tissuespecific adult stem cells and the ability to reprogram somatic cells have fascinated researchers [164,173] . Ever since Yamanaka demonstrated that Oct4, Sox2, Klf4, and c-Myc can convert mouse fibroblasts into induced pluripotent stem cells (iPSCs) [5] , the study of reprogramming has accelerated with the use of epigenetic process modulators, which target histone deacetylase (HDAC) [174,175] , histone acetyltransferase (HMT) [176,177] , and DNA methyltransferase (DNMT) [176,178] . Recently, a chemical cocktail including HDAC inhibitors and other kinase inhibitors enhanced the reprogramming efficiency of human fibroblasts [175,179] .…”

Section: Small Molecules and Stem Cell Fatementioning

confidence: 99%

MicroRNAs as novel regulators of stem cell fate

Choi

Hwang³

2013

WJSC

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Mounting evidence in stem cell biology has shown that microRNAs (miRNAs) play a crucial role in cell fate specification, including stem cell self-renewal, lineagespecific differentiation, and somatic cell reprogramming. These functions are tightly regulated by specific gene expression patterns that involve miRNAs and transcription factors. To maintain stem cell pluripotency, specific miRNAs suppress transcription factors that promote differentiation, whereas to initiate differentiation, lineagespecific miRNAs are upregulated via the inhibition of transcription factors that promote self-renewal. Small molecules can be used in a similar manner as natural miRNAs, and a number of natural and synthetic small molecules have been isolated and developed to regulate stem cell fate. Using miRNAs as novel regulators of stem cell fate will provide insight into stem cell biology and aid in understanding the molecular mechanisms and crosstalk between miRNAs and stem cells.Ultimately, advances in the regulation of stem cell fate will contribute to the development of effective medical therapies for tissue repair and regeneration. This review summarizes the current insights into stem cell fate determination by miRNAs with a focus on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.© 2013 Baishideng. All rights reserved. Key words:MicroRNA; Stem cell fate; Differentiation; Self-renewal; Reprogramming; Small molecule Core tip: Stem cells are important in regenerative medicine applications due to their capacity to self-renew and differentiate into specific cell types. MicroRNAs (miRNAs) are short non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Recent studies suggest that miRNAs are key molecules in the regulation of stem cell fate decisions; this regulation is manifested as the fine tuning of cell-and tissue-specific gene expression. This review summarizes the current insights into stem cell fate determination by miRNAs and focuses on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.

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Section: Small Molecules and Stem Cell Fatementioning

confidence: 99%

MicroRNAs as novel regulators of stem cell fate

Choi

Hwang³

2013

WJSC

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“…The hypoxic condition and its effector gene, hypoxia-inducible factor 1a, which is extensively linked to promoting glycolytic metabolism, can also enhance the reprogramming efficiencies of both mouse and human cells. 40,81 Several other small molecules, such as A83-01 (TGF-b inhibitor), 43,70 3-deazaneplanocin (epigenetic modulator), 17 2,4-dinitrophenol (DNP, oxidative phosphorylation uncoupler), 43 RSC133 (DNMT inhibitor), 82 rapamycin (mTOR inhibitor), 83 compound B6 (AKT-mediated inhibitor of GSK3-b), 84 compound B8 (inositol triphosphate 3-kinase inhibitor), 84 compound B10 (P38 kinase inhibitor), 84 and vitamin C, 70 can facilitate the reprogramming efficiency of somatic cells into mouse and/or human iPSCs (Table 2).…”

Section: Small Molecules That Can Replace Klf4 and C-mycmentioning

confidence: 99%

Generation of pluripotent stem cells without the use of genetic material

Higuchi

Ling

Kumar

et al. 2015

Laboratory Investigation

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Induced pluripotent stem cells (iPSCs) provide a platform to obtain patient-specific cells for use as a cell source in regenerative medicine. Although iPSCs do not have the ethical concerns of embryonic stem cells, iPSCs have not been widely used in clinical applications, as they are generated by gene transduction. Recently, iPSCs have been generated without the use of genetic material. For example, protein-induced PSCs and chemically induced PSCs have been generated by the use of small and large (protein) molecules. Several epigenetic characteristics are important for cell differentiation; therefore, several small-molecule inhibitors of epigenetic-modifying enzymes, such as DNA methyltransferases, histone deacetylases, histone methyltransferases, and histone demethylases, are potential candidates for the reprogramming of somatic cells into iPSCs. In this review, we discuss what types of small chemical or large (protein) molecules could be used to replace the viral transduction of genes and/or genetic reprogramming to obtain human iPSCs.

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“…Modifying or supplementing the core OSKM with other factors or small molecules (35, 36) influencing pluripotency, proliferation, and epigenetic remodeling have been shown to enhance the quality and efficiency of reprograming, in both mouse and human iPSCs, as well as promote pluripotency maintenance during culturing [reviewed in Ref. (37)].…”

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 99%

Generation of Thyroid Follicular Cells from Pluripotent Stem Cells: Potential for Regenerative Medicine

Sewell

Lin

2014

Front. Endocrinol.

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Nearly 12% of the population in the United States will be afflicted with a thyroid related disorder during their lifetime. Common treatment approaches are tailored to the specific disorder and include surgery, radioactive iodine ablation, antithyroid drugs, thyroid hormone replacement, external beam radiation, and chemotherapy. Regenerative medicine endeavors to combat disease by replacing or regenerating damaged, diseased, or dysfunctional body parts. A series of achievements in pluripotent stem cell research have transformed regenerative medicine in many ways by demonstrating “repair” of a number of body parts in mice, of which, the thyroid has now been inducted into this special group. Seminal work in pluripotent cells, namely embryonic stem cells and induced pluripotent stem cells, have made possible their path to becoming key tools and biological building blocks for cell-based regenerative medicine to combat the gamut of human diseases, including those affecting the thyroid.

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A Novel Small Molecule Facilitates the Reprogramming of Human Somatic Cells into a Pluripotent State and Supports the Maintenance of an Undifferentiated State of Human Pluripotent Stem Cells

Cited by 42 publications

References 31 publications

MicroRNAs as novel regulators of stem cell fate

MicroRNAs as novel regulators of stem cell fate

Generation of pluripotent stem cells without the use of genetic material

Generation of Thyroid Follicular Cells from Pluripotent Stem Cells: Potential for Regenerative Medicine

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