Pluripotent Stem Cells Derived From Mouse Primordial Germ Cells by Small Molecule Compounds

Kimura, Tohru; Kaga, Yoshiaki; Sekita, Yoichi; Fujikawa, Keita; Nakatani, Tsunetoshi; Odamoto, Mika; Funaki, Soichiro; Ikawa, Masahito; Abe, Kuniya; Nakano, Tsutomu

doi:10.1002/stem.1838

Cited by 28 publications

(26 citation statements)

References 43 publications

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“…However, unlike mouse EGCs, human EGCs exhibit very low derivation efficiencies and are unstable under the current cell culture methods. More recently, PGCs have been induced to become pluripotent EGCs using small molecules TGFbR inhibitor and/or kempaullone [60]. However, the in vivo function of induced pluripotent EGCs has not been successfully demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Direct Reprogramming of Human Primordial Germ Cells into Induced Pluripotent Stem Cells: Efficient Generation of Genetically Engineered Germ Cells

Bazley

Liu

Yuan

et al. 2015

Stem Cells and Development

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Primordial germ cells (PGCs) share many properties with embryonic stem cells (ESCs) and innately express several key pluripotency-controlling factors, including OCT4, NANOG, and LIN28. Therefore, PGCs may provide a simple and efficient model for studying somatic cell reprogramming to induced pluripotent stem cells (iPSCs), especially in determining the regulatory mechanisms that fundamentally define pluripotency. Here, we report a novel model of PGC reprogramming to generate iPSCs via transfection with SOX2 and OCT4 using integrative lentiviral. We also show the feasibility of using nonintegrative approaches for generating iPSC from PGCs using only these two factors. We show that human PGCs express endogenous levels of KLF4 and C-MYC protein at levels similar to embryonic germ cells (EGCs) but lower levels of SOX2 and OCT4. Transfection with both SOX2 and OCT4 together was required to induce PGCs to a pluripotent state at an efficiency of 1.71%, and the further addition of C-MYC increased the efficiency to 2.33%. Immunohistochemical analyses of the SOderived PGC-iPSCs revealed that these cells were more similar to ESCs than EGCs regarding both colony morphology and molecular characterization. Although leukemia inhibitory factor (LIF) was not required for the generation of PGC-iPSCs like EGCs, the presence of LIF combined with ectopic exposure to C-MYC yielded higher efficiencies. Additionally, the SO-derived PGC-iPSCs exhibited differentiation into representative cell types from all three germ layers in vitro and successfully formed teratomas in vivo. Several lines were generated that were karyotypically stable for up to 24 subcultures. Their derivation efficiency and survival in culture significantly supersedes that of EGCs, demonstrating their utility as a powerful model for studying factors regulating pluripotency in future studies.

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Section: Discussionmentioning

confidence: 99%

Direct Reprogramming of Human Primordial Germ Cells into Induced Pluripotent Stem Cells: Efficient Generation of Genetically Engineered Germ Cells

Bazley

Liu

Yuan

et al. 2015

Stem Cells and Development

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“…When postmigratory PGCs at E11.5 are treated with TGFβRi under ESC culture conditions, EGCs can be derived without KITLG and bFGF, showing that TGFβRi can reproduce the effects of KITLG and bFGF [62] .…”

Section: Reprogramming By Small Molecule Compoundsmentioning

confidence: 98%

Reprogramming of germ cells into pluripotency

Sekita¹,

Nakamura²,

Kimura³

2016

WJSC

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Primordial germ cells (PGCs) are precursors of all gametes, and represent the founder cells of the germline. Although developmental potency is restricted to germ-lineage cells, PGCs can be reprogrammed into a pluripotent state. Specifically, PGCs give rise to germ cell tumors, such as testicular teratomas, in vivo , and to pluripotent stem cells known as embryonic germ cells in vitro . In this review, we highlight the current knowledge on signaling pathways, transcriptional controls, and post-transcriptional controls that govern germ cell differentiation and de-differentiation. These regulatory processes are common in the reprogramming of germ cells and somatic cells, and play a role in the pathogenesis of human germ cell tumors.

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“…Growth factors including LIF, bFGF and SCF are essential for the derivation of porcine EGCs [39] . PGCs could be reprogrammed into iEGCs using small molecules and transcription factors of OCT4 and C-MYC [53] . In addition, hypoxia induces reprogramming of PGCs by deregulating expression of OCT4 [54] .…”

Section: Derivation Of Pluripotent Stem Cells From Primordial Germ Cellsmentioning

confidence: 99%

Porcine pluripotent stem cells: progress, challenges and prospects

Han¹,

Miao²,

Hua³

et al. 2019

Front. Agr. Sci. Eng.

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Pluripotent stem cells (PSCs) are characterized by their capacity for high self-renewal and multiple differentiation potential and include embryonic stem cells, embryonic germ cells and induced PSCs. PSCs provide a very suitable model for the studies of human diseases, drugs screening, regenerative medicine and developmental biology research. Pigs are considered as an ideal model for preclinical development of human xenotransplantation, therapeutic approaches and regenerative medicine because of their size and physiological similarity to humans. However, lack of knowledge about the derivation, characterization and pluripotency mechanisms of porcine PSCs hinders progress in these biotechnologies. In this review, we discuss the latest progress on porcine PSCs generation, evaluation criteria for pluripotency, the scientific and technical questions arising from these studies. We also introduce our perspectives on porcine PSC research, in the hope of providing new ideas for generating naive porcine PSCs and animal breeding.

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Pluripotent Stem Cells Derived From Mouse Primordial Germ Cells by Small Molecule Compounds

Cited by 28 publications

References 43 publications

Direct Reprogramming of Human Primordial Germ Cells into Induced Pluripotent Stem Cells: Efficient Generation of Genetically Engineered Germ Cells

Direct Reprogramming of Human Primordial Germ Cells into Induced Pluripotent Stem Cells: Efficient Generation of Genetically Engineered Germ Cells

Reprogramming of germ cells into pluripotency

Porcine pluripotent stem cells: progress, challenges and prospects

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