Abstract
Somatic cells can be reprogrammed to generate induced pluripotent stem cells (iPSCs) by overexpression of four transcription factors, Oct4, Klf4, Sox2, and c-Myc. However, exogenous expression of pluripotency factors raised concerns for clinical applications. Here, we show that iPS-like cells (iPSLCs) were generated from mouse somatic cells in two steps with small molecule compounds. In the first step, stable intermediate cells were generated from mouse astrocytes by Bmi1. These cells called induced epiblast stem cell (EpiSC)-like cells (iEpiSCLCs) are similar to EpiSCs in terms of expression of specific markers, epigenetic state, and ability to differentiate into three germ layers. In the second step, treatment with MEK/ERK and GSK3 pathway inhibitors in the presence of leukemia inhibitory factor resulted in conversion of iEpiSCLCs into iPSLCs that were similar to mESCs, suggesting that Bmi1 is sufficient to reprogram astrocytes to partially reprogrammed pluripotency. Next, Bmi1 function was replaced with Shh activators (oxysterol and purmorphamine), which demonstrating that combinations of small molecules can compensate for reprogramming factors and are sufficient to directly reprogram mouse somatic cells into iPSLCs. The chemically induced pluripotent stem cell-like cells (ciPSLCs) showed similar gene expression profiles, epigenetic status, and differentiation potentials to mESCs.
Original language | English |
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Pages (from-to) | 7336-7345 |
Number of pages | 10 |
Journal | Biomaterials |
Volume | 35 |
Issue number | 26 |
DOIs | |
Publication status | Published - 2014 Aug |
Bibliographical note
Funding Information:This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation of Korea funded by the Korean Ministry of Science, ICT & Future Planning (MSIP) NRF-2010-0020347, a grant of the Korea Health Technology R&D Project, Ministry of Health & Welfare Grant A120392 and School of Life Sciences and Biotechnology for BK21 PLUS, Korea University .
Keywords
- Bmi1
- Induced pluripotent stem cell (iPSC)
- Reprogramming
- Small molecule compounds
ASJC Scopus subject areas
- Biophysics
- Bioengineering
- Ceramics and Composites
- Biomaterials
- Mechanics of Materials