Chemical induced conversion of mouse fibroblasts and human adipose-derived stem cells into skeletal muscle-like cells

Bansal, Varun; De, Debojyoti; An, Jieun; Kang, Tong Mook; Jeong, Hyeon‐Ju; Kang, Jong‐Sun; Kim, Kyeong Kyu

doi:10.1016/j.biomaterials.2018.11.037

Cited by 26 publications

(22 citation statements)

References 26 publications

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“…Moreover, since the chemicals C, 6, F, and their combinations have been widely used in different chemical reprogramming systems and generate many different cell fates 8 , 12 , 13 , 15 – 17 , 19 , 20 , it is still unclear whether Sox17 activation is a specific outcome of the chemical treatment and whether these chemicals can prime the cells and facilitate cell fate conversion into other lineages simultaneously. These are some of the questions we intend to address in our future study.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, chemical reprogramming strategies have been extended to inducing direct cell lineage conversion into functional cell types without an intermediate pluripotent state. For instance, neural progenitors 10 , functional neurons 11 , 12 , cardiomyocytes 13 , 14 , skeletal muscles 15 , brown adipocytes 16 , 17 , astrocytes 18 , endoderm progenitor-like cells 19 , and photoreceptor-like cells 20 are reported to be induced from fibroblasts with chemicals alone. Besides, endoderm progenitor cells are induced from gut epithelium with pure chemicals 21 , and human fetal astrocytes are converted into functional neurons by chemical combinations 22 .…”

Section: Introductionmentioning

confidence: 99%

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Chemicals orchestrate reprogramming with hierarchical activation of master transcription factors primed by endogenous Sox17 activation

Yang

et al. 2020

Commun Biol

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Mouse somatic cells can be chemically reprogrammed into pluripotent stem cells (CiPSCs) through an intermediate extraembryonic endoderm (XEN)-like state. However, it is elusive how the chemicals orchestrate the cell fate alteration. In this study, we analyze molecular dynamics in chemical reprogramming from fibroblasts to a XEN-like state. We find that Sox17 is initially activated by the chemical cocktails, and XEN cell fate specialization is subsequently mediated by Sox17 activated expression of other XEN master genes, such as Sall4 and Gata4. Furthermore, this stepwise process is differentially regulated. The core reprogramming chemicals CHIR99021, 616452 and Forskolin are all necessary for Sox17 activation, while differently required for Gata4 and Sall4 expression. The addition of chemical boosters in different phases further improves the generation efficiency of XEN-like cells. Taken together, our work demonstrates that chemical reprogramming is regulated in 3 distinct “prime–specify–transit” phases initiated with endogenous Sox17 activation, providing a new framework to understand cell fate determination.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chemicals orchestrate reprogramming with hierarchical activation of master transcription factors primed by endogenous Sox17 activation

Yang

et al. 2020

Commun Biol

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“…The cell therapy technique brings a promising approach to resolve this issue. Recently, it was reported that mouse fibroblasts could be converted to skeletal muscle cells by a combination of six small molecules (VPA, Chir99021, RepSox, Forskolin, Parnate, and TTNPB) [ 69 ]. The authors implied that three signaling pathways Wnt, TGF- β , and cAMP were crucial for the transdifferentiation.…”

Section: Transdifferentiation In Vitromentioning

confidence: 99%

Small Molecule Epigenetic Modulators in Pure Chemical Cell Fate Conversion

Yuan

Zhu

Liu

et al. 2020

Stem Cells International

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Although innovative technologies for somatic cell reprogramming and transdifferentiation provide new strategies for the research of translational medicine, including disease modeling, drug screening, artificial organ development, and cell therapy, recipient safety remains a concern due to the use of exogenous transcription factors during induction. To resolve this problem, new induction approaches containing clinically applicable small molecules have been explored. Small molecule epigenetic modulators such as DNA methylation writer inhibitors, histone methylation writer inhibitors, histone acylation reader inhibitors, and histone acetylation eraser inhibitors could overcome epigenetic barriers during cell fate conversion. In the past few years, significant progress has been made in reprogramming and transdifferentiation of somatic cells with small molecule approaches. In the present review, we systematically discuss recent achievements of pure chemical reprogramming and transdifferentiation.

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“…To eliminate the possibility that contaminating endocrine progenitors were present in the starting MEF cells and confirm that the differentiated β-like cells indeed originated from the MEFs, we performed a lineage tracing experiment in a way similar to that previously reported [36]. We crossed Fsp1-cre and R26RtdTomato mice to acquire Fsp1-tdTomato offspring in whom tdTomato expression was under the control of the Fsp1 promoter.…”

Section: Lineage Tracing Revealed the Fibroblastic Origin Of The Diffmentioning

confidence: 99%

“…Therefore, only cells originating from fibroblasts expressed tdTomato (red fluorescence) (Supplementary Figure S3A). tdTomato-MEFs were harvested [36] and the cells were divided into small molecule only, exosome only, and exosome + small molecule groups in stage 1 and differentiated according to our protocol ( Figure 1A). At the end of stage 3, the cells were stained to assess their C-peptide protein levels.…”

Section: Lineage Tracing Revealed the Fibroblastic Origin Of The Diffmentioning

confidence: 99%

Exosome-Mediated Differentiation of Mouse Embryonic Fibroblasts and Exocrine Cells into β-Like Cells and the Identification of Key miRNAs for Differentiation

Mandal

et al. 2020

Biomedicines

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Diabetes is a concerning health malady worldwide. Islet or pancreas transplantation is the only long-term treatment available; however, the scarcity of transplantable tissues hampers this approach. Therefore, new cell sources and differentiation approaches are required. Apart from the genetic- and small molecule-based approaches, exosomes could induce cellular differentiation by means of their cargo, including miRNA. We developed a chemical-based protocol to differentiate mouse embryonic fibroblasts (MEFs) into β-like cells and employed mouse insulinoma (MIN6)-derived exosomes in the presence or absence of specific small molecules to encourage their differentiation into β-like cells. The differentiated β-like cells were functional and expressed pancreatic genes such as Pdx1, Nkx6.1, and insulin 1 and 2. We found that the exosome plus small molecule combination differentiated the MEFs most efficiently. Using miRNA-sequencing, we identified miR-127 and miR-709, and found that individually and in combination, the miRNAs differentiated MEFs into β-like cells similar to the exosome treatment. We also confirmed that exocrine cells can be differentiated into β-like cells by exosomes and the exosome-identified miRNAs. A new differentiation approach based on the use of exosome-identified miRNAs could help people afflicted with diabetes

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Chemical induced conversion of mouse fibroblasts and human adipose-derived stem cells into skeletal muscle-like cells

Cited by 26 publications

References 26 publications

Chemicals orchestrate reprogramming with hierarchical activation of master transcription factors primed by endogenous Sox17 activation

Chemicals orchestrate reprogramming with hierarchical activation of master transcription factors primed by endogenous Sox17 activation

Small Molecule Epigenetic Modulators in Pure Chemical Cell Fate Conversion

Exosome-Mediated Differentiation of Mouse Embryonic Fibroblasts and Exocrine Cells into β-Like Cells and the Identification of Key miRNAs for Differentiation

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