Recent Advances in Stem and Germ Cell Research: Implications for the Derivation of Pig Pluripotent Cells

Alberio, Ramiro; Pérez, A. Tabasco

doi:10.1111/j.1439-0531.2012.02062.x

Cited by 13 publications

(8 citation statements)

References 105 publications

(202 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, establishment of ESCs and reprogramming of somatic cells in pig has been hampered by differences in the molecular mechanisms of embryo development among mouse, human, and pig. During development of the early embryo, pig has a distinct features of preimplantation stages compared with mouse and human (Alberio and Perez, 2012). It has been surmised that unique cellular signaling networks are involved in establishing and maintaining pluripotency during pig embryo development.…”

Section: Discussionmentioning

confidence: 99%

“…Since the 1990s, much effort has focused on deriving genuine pig ESCs from early embryos; however, the cell lines produced did not meet the required criteria, especially in vivo developmental competency such as chimera and teratoma formation (Ezashi et al., 2016), possibly due to the lack of optimized culture medium. During development of the early embryo, which has the inner cell mass (ICM), considered as pluripotent founder population, the pig has a longer preimplantation period compared with mouse and human (Alberio and Perez, 2012). Therefore, in the pig embryo the cell-signaling network that governs pluripotency has different patterns compared with the mouse embryo (Hall and Hyttel, 2014, Liu et al., 2015).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Chemically Defined Media Can Maintain Pig Pluripotency Network In Vitro

et al. 2019

View full text Add to dashboard Cite

Summary Pig embryonic stem cells (pESCs) have been considered an important candidate for preclinical research on human therapies. However, the lack of understanding of pig pluripotent networks has hampered establishment of authentic pESCs. Here, we report that FGF2, ACTVIN, and WNT signaling are essential to sustain pig pluripotency in vitro . Newly derived pESCs were stably maintained over an extended period, and capable of forming teratomas that contained three germ layers. Transcriptome analysis showed that pESCs were developmentally similar to late epiblasts of preimplantation embryos and in terms of biological functions resembled human rather than mouse pluripotent stem cells. However, the pESCs had distinct features such as coexpression of SSEA1 and SSEA4, two active X chromosomes, and a unique transcriptional pattern. Our findings will facilitate both the development of large animal models for human stem cell therapy and the generation of pluripotent stem cells from other domestic animals for agricultural use.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chemically Defined Media Can Maintain Pig Pluripotency Network In Vitro

et al. 2019

View full text Add to dashboard Cite

show abstract

“…However, it is challenging to establish porcine ESCs and optimize pig-specific reprogramming conditions using typical methods because of differences in the genetic backgrounds of mouse, human, and pig. During development of the early embryo, which has an inner cell mass (ICM) considered to be the pluripotent cell population, pig has a prolonged preimplantation period compared with mouse and human [ 28 ]. Therefore, in pig embryos, different cell signaling that governs pluripotency reveals differences compared to mouse embryos.…”

Section: Discussionmentioning

confidence: 99%

“…Although various research groups have attempted to generate pig iPSCs (piPSCs), authentic iPSCs have not be obtained, instead showing features of incomplete reprogramming including dependence on transgene expression, epigenetic remodeling, reactivation of pluripotent genes, and chimera formation [ 22 – 27 ]. This may be due to differences in the molecular mechanisms during embryo development between mouse and pig [ 28 ]. It is important to investigate pre-iPSCs to improve and develop reprogramming methods by understanding reprogramming mechanisms in pig.…”

Section: Introductionmentioning

confidence: 99%

Reactivation of Endogenous Genes and Epigenetic Remodeling Are Barriers for Generating Transgene-Free Induced Pluripotent Stem Cells in Pig

et al. 2016

View full text Add to dashboard Cite

Cellular reprogramming of committed cells into a pluripotent state can be induced by ectopic expression of genes such as OCT4, SOX2, KLF4, and MYC. Reprogrammed cells can be maintained by activating endogenous pluripotent networks without transgene expression. Although various research groups have attempted to generate pig induced pluripotent stem cells (iPSCs), authentic iPSCs have not be obtained, instead showing dependence on transgene expression. In this study, iPSCs were derived from porcine fetal fibroblasts via drug-inducible vectors carrying human transcription factors (OCT4, SOX2, KLF4, and MYC). Therefore, this study investigated characteristics of iPSCs and reprogramming mechanisms in pig. The iPSCs were stably maintained over an extended period with potential in vitro differentiation into three germ layers. In addition, the pluripotent state of iPSCs was regulated by modulating culture conditions. They showed naive- or primed-like pluripotent states in LIF or bFGF supplemented culture conditions, respectively. However, iPSCs could not be maintained without ectopic expression of transgenes. The cultured iPSCs expressed endogenous transcription factors such as OCT4 and SOX2, but not NANOG (a known gateway to complete reprogramming). 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 occur in female iPSCs. Based on our results, expression of exogenous genes could not sufficiently activate the essential endogenous genes and remodel the epigenetic milieu to achieve faithful pluripotency in pig. Accordingly, investigating iPSCs could help us improve and develop reprogramming methods by understanding reprogramming mechanisms in pig.

show abstract

“…This relocation also occurs simultaneously with a loss in androgen sensitivity (Pinto et al 2010). The pig is another animal model in which early steps of germ cell development have been studied, because of their potential use in derivating pluripotent cells for the generation of transgenic farm animals (Alberio & Perez 2012). In pigs, gonocytes will proliferate, migrate to the basement membrane of the tubules, and differentiate to SSCs during the first 3 months of life.…”

Section: Insights From Non-rodent Speciesmentioning

confidence: 99%

Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges

Manku¹,

Culty²

2015

Reproduction

127

105

View full text Add to dashboard Cite

The production of spermatozoa relies on a pool of spermatogonial stem cells (SSCs), formed in infancy from the differentiation of their precursor cells, the gonocytes. Throughout adult life, SSCs will either self-renew or differentiate, in order to maintain a stem cell reserve while providing cells to the spermatogenic cycle. By contrast, gonocytes represent a transient and finite phase of development leading to the formation of SSCs or spermatogonia of the first spermatogenic wave. Gonocyte development involves phases of quiescence, cell proliferation, migration, and differentiation. Spermatogonia, on the other hand, remain located at the basement membrane of the seminiferous tubules throughout their successive phases of proliferation and differentiation. Apoptosis is an integral part of both developmental phases, allowing for the removal of defective cells and the maintenance of proper germ-Sertoli cell ratios. While gonocytes and spermatogonia mitosis are regulated by distinct factors, they both undergo differentiation in response to retinoic acid. In contrast to postpubertal spermatogenesis, the early steps of germ cell development have only recently attracted attention, unveiling genes and pathways regulating SSC self-renewal and proliferation. Yet, less is known on the mechanisms regulating differentiation. The processes leading from gonocytes to spermatogonia have been seldom investigated. While the formation of abnormal gonocytes or SSCs could lead to infertility, defective gonocyte differentiation might be at the origin of testicular germ cell tumors. Thus, it is important to better understand the molecular mechanisms regulating these processes. This review summarizes and compares the present knowledge on the mechanisms regulating mammalian gonocyte and spermatogonial differentiation.

show abstract

Recent Advances in Stem and Germ Cell Research: Implications for the Derivation of Pig Pluripotent Cells

Cited by 13 publications

References 105 publications

Chemically Defined Media Can Maintain Pig Pluripotency Network In Vitro

Chemically Defined Media Can Maintain Pig Pluripotency Network In Vitro

Reactivation of Endogenous Genes and Epigenetic Remodeling Are Barriers for Generating Transgene-Free Induced Pluripotent Stem Cells in Pig

Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges

Contact Info

Product

Resources

About