642 Phenotypic Comparison of Hepatocyte-Like Cells Differentiated From Human Induced Pluripotent Stem Cells Derived by Cellular Reprogramming of Primary Hepatocytes and Dermal Fibroblasts Obtained From the Same Donor

Human dermal fibroblasts obtained by skin biopsy can be reprogrammed directly to pluripotency by the ectopic expression of defined transcription factors. Here, we describe the derivation of induced pluripotent stem cells from CD34+ mobilized human peripheral blood cells using retroviral transduction of OCT4/SOX2/KLF4/MYC. Blood-derived human induced pluripotent stem cells are indistinguishable from human embryonic stem cells with respect to morphology, expression of surface antigens, and pluripotency-associated transcription factors, DNA methylation status at pluripotent cell-specific genes, and the capacity to differentiate in vitro and in teratomas. The ability to reprogram cells from human blood will allow the generation of patient-specific stem cells for diseases in which the disease-causing somatic mutations are restricted to cells of the hematopoietic lineage.

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Generation and Characterization of LIF-dependent Canine Induced Pluripotent Stem Cells from Adult Dermal Fibroblasts

Stem Cells and Development ◽

10.1089/scd.2011.0608 ◽

2012 ◽

Vol 21 (12) ◽

pp. 2288-2297 ◽

Cited By ~ 45

Author(s):

Deanne J. Whitworth ◽

Dmitry A. Ovchinnikov ◽

Ernst J. Wolvetang

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Dermal Fibroblasts ◽

Induced Pluripotent

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Generation of human induced pluripotent stem cells from dermal fibroblasts

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0711983105 ◽

2008 ◽

Vol 105 (8) ◽

pp. 2883-2888 ◽

Cited By ~ 715

Author(s):

W. E. Lowry ◽

L. Richter ◽

R. Yachechko ◽

A. D. Pyle ◽

J. Tchieu ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Dermal Fibroblasts ◽

Induced Pluripotent

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Effect of Hepatic Differentiation on Fatty Acid Composition of Induced Pluripotent Stem Cells Derived from Human Dermal Fibroblasts

Istanbul Medical Journal ◽

10.5152/imj.2018.60465 ◽

2018 ◽

Vol 19 (2) ◽

pp. 113-118

Author(s):

Nasim Parsafam ◽

◽

Yagoub Rahimi ◽

Amir Mehdizadeh ◽

Hojjatollah Nozad Charoudeh ◽

...

Keyword(s):

Stem Cells ◽

Fatty Acid Composition ◽

Fatty Acid ◽

Induced Pluripotent Stem Cells ◽

Acid Composition ◽

Pluripotent Stem Cells ◽

Dermal Fibroblasts ◽

Human Dermal Fibroblasts ◽

Hepatic Differentiation ◽

Induced Pluripotent

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Overcoming barriers to reprogramming and differentiation in nonhuman primate induced pluripotent stem cells

Primate Biology ◽

10.5194/pb-4-153-2017 ◽

2017 ◽

Vol 4 (2) ◽

pp. 153-162 ◽

Cited By ~ 2

Author(s):

Jacob J. Hemmi ◽

Anuja Mishra ◽

Peter J. Hornsby

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Dimethyl Sulfoxide ◽

Pluripotent Stem Cells ◽

Ips Cells ◽

Cellular Reprogramming ◽

Biological Research ◽

Differentiation Potential ◽

Wide Range ◽

Induced Pluripotent

Abstract. Induced pluripotent stem cells (iPS cells) generated by cellular reprogramming from nonhuman primates (NHPs) are of great significance for regenerative medicine and for comparative biology. Autologously derived stem cells would theoretically avoid any risk of rejection due to host–donor mismatch and may bypass the need for immune suppression post-transplant. In order for these possibilities to be realized, reprogramming methodologies that were initially developed mainly for human cells must be translated to NHPs. NHP studies have typically used pluripotent cells generated from young animals and thus risk overlooking complications that may arise from generating iPS cells from donors of other ages. When reprogramming is extended to a wide range of NHP species, available donors may be middle- or old-aged. Here we have pursued these questions by generating iPS cells from donors across the life span of the common marmoset (Callithrix jacchus) and then subjecting them to a directed neural differentiation protocol. The differentiation potential of different clonal cell lines was assessed using the quantitative polymerase chain reaction. The results show that cells derived from older donors often showed less neural marker induction. These deficits were rescued by a 24 h pretreatment of the cells with 0.5 % dimethyl sulfoxide. Another NHP that plays a key role in biological research is the chimpanzee (Pan troglodytes). iPS cells generated from the chimpanzee can be of great interest in comparative in vitro studies. We investigated if similar deficits in differentiation potential might arise in chimpanzee iPS cells reprogrammed using various technologies. The results show that, while some deficits were observed in iPS cell clones generated using three different technologies, there was no clear association with the vector used. These deficits in differentiation were also prevented by a 24 h pretreatment with 0.5 % dimethyl sulfoxide.

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222 INCOMPLETE REPROGRAMMING OF INDUCED PLURIPOTENT STEM CELLS DERIVED FROM PORCINE FETAL FIBROBLASTS

Reproduction Fertility and Development ◽

10.1071/rdv28n2ab222 ◽

2016 ◽

Vol 28 (2) ◽

pp. 242

Author(s):

K.-H. Choi ◽

D. Son ◽

D.-K. Lee ◽

J.-N. Oh ◽

S.-H. Kim ◽

...

Keyword(s):

Stem Cells ◽

Transcription Factors ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Ectopic Expression ◽

Cellular Reprogramming ◽

Pluripotent State ◽

Fetal Fibroblasts ◽

Endogenous Genes ◽

Induced Pluripotent

Cellular reprogramming of committed cells into a pluripotent state can be accomplished by ectopic expression of genes such as OCT4, SOX2, KLF4, and MYC. However, during reprogramming, it has been verified that failures of reactivating endogenous genes and epigenetic remodelling lead to partially reprogrammed cells exhibiting features similar to those of fully reprogrammed cells. In this study, partially reprogrammed induced pluripotent stem cells (pre-iPSC) were derived from porcine fetal fibroblasts via drug-inducible vector carrying human transcription factors (OCT4, SOX2, KLF4, and MYC). Therefore, this study aimed to investigate characteristics of pre-iPSC and reprogramming mechanisms. The pre-iPSC were stably maintained over an extended period having in vitro differentiation ability into 3 germ layers. The pluripotent state of pre-iPSC was regulated by modulation of culture condition. They showed naive- or primed-like pluripotent state in leukemia inhibitory factor (LIF) or basic fibroblast growth factor (bFGF) supplemented culture conditions respectively. However, pre-iPSC could not be maintained without ectopic expression of transgenes. The cultured pre-iPSC expressed endogenous transcription factors (OCT4 and SOX2) except for NANOG known as gateway into complete reprogramming. In addition, endogenous genes related to mesenchymal-to-epithelial transition (DPPA2, CDH1, EPCAM, and OCLN) were not sufficiently reactivated as measured by qPCR. DNA methylation analysis for promoters of OCT4, NANOG, and XIST showed that epigenetic reprogramming did not occurred in female pre-iPSC. Given the results, we found that expression of exogenous genes could not sufficiently activate the essential endogenous genes and remodel the epigenetic milieu for achieving faithful pluripotency in pig. Accordingly, investigating pre-iPSC could help us to improve and develop reprogramming methods via understanding reprogramming mechanisms in pig. This work was supported by the Next-generation BioGreen 21 Program (PJ0113002015), Rural Development Administration, Republic of Korea.

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