Pluripotent Cell Models for Gonadal Research

Gutiérrez, Daniel Rodríguez; Biason‐Lauber, Anna

doi:10.3390/ijms20215495

Cited by 8 publications

(4 citation statements)

References 136 publications

(157 reference statements)

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“…Due to the complexity of sex development itself, a proper cell model has been searched for, for many years, to properly mimic patients' phenotypes and study DSD-related candidate genes and role of candidate variants. Nowadays, new techniques based on cell reprograming and in vitro guided differentiation (from differentiated cells to pluripotent stem cells to redifferentiated cells again) open the field to adequate models for DSD in the near future to predict the role of candidate variants [57][58][59].…”

Section: Perspectives and Pitfallsmentioning

confidence: 99%

Oligogenic Origin of Differences of Sex Development in Humans

Camats

Flück

Audí

2020

IJMS

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Sex development is a very complex biological event that requires the concerted collaboration of a large network of genes in a spatial and temporal correct fashion. In the past, much has been learned about human sex development from monogenic disorders/differences of sex development (DSD), but the broad spectrum of phenotypes in numerous DSD individuals remains a conundrum. Currently, the genetic cause of less than 50% of DSD individuals has been solved and oligogenic disease has been proposed. In recent years, multiple genetic hits have been found in individuals with DSD thanks to high throughput sequencing. Our group has been searching for additional genetic hits explaining the phenotypic variability over the past years in two cohorts of patients: 46,XY DSD patients carriers of NR5A1 variants and 46,XY DSD and 46,XX DSD with MAMLD1 variants. In both cohorts, our results suggest that the broad phenotypes may be explained by oligogenic origin, in which multiple hits may contribute to a DSD phenotype, unique to each individual. A search for an underlying network of the identified genes also revealed that a considerable number of these genes showed interactions, suggesting that genetic variations in these genes may affect sex development in concert.

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Section: Perspectives and Pitfallsmentioning

confidence: 99%

Oligogenic Origin of Differences of Sex Development in Humans

Camats

Flück

Audí

2020

IJMS

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“…FSH, follicle-stimulating hormone; GDF9, growth differentiation factor 9; BMP4, bone morphogenetic protein 4; TGF β, transforming growth factor β. Modified from (Rodriguez Gutierrez and Biason-Lauber, 2019). …”

Section: Introductionmentioning

confidence: 99%

Generation of a human ovarian granulosa cell model from induced pluripotent stem cells

Hart

Gutiérrez

Biason‐Lauber

2022

Preprint

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SUMMARYSex development is an intricate and crucial process in all vertebrates that ensures the continued propagation of genetic diversity within a species, and ultimately their survival. Perturbations in this process can manifest as variations/differences of sex development (VSD/DSD). Primary gonadal somatic cells – the ovarian granulosa cells (GCs) in the case of women – represent the absolute model to investigate mechanism of disease in VSDs. Collection of these cells in humans is laborious and invasive, while classical animal models fail to recapitulate the human phenotype and function. Furthermore, in patients with the most severe forms of VSD gonadal cells are totally absent. It is therefore vital to develop an alternative cell-model. In view of this, we established an efficient method to reprogram donor-derived urinary progenitor cells (UPs) and differentiate iPSCs into granulosa-like cells (GLCs). The UPs presented a less invasive and high-quality cell source, improving the clinical applicability of the model along with utilising a non-integrative reprogramming method that eliminates alteration of the original genome. This novel GLC model closely resembles human GCs in morphology and marker gene expression of GC cell-fate and essential function. These results provide the prospect to generate patient-specific personalised GC models to investigate mechanism of disease in VSDs and could improve understanding of the intricacies in female gonadal development.

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“…A mouse model is most commonly used to study mammalian female GCs formation, specialization, and differentiation [ 3 ]. Significant achievements have been gained in inducing mouse female GCs from pluripotent stem cells (PSCs) which provide remarkable references for reconstructing human female GCs in vitro from PSCs [ 4 – 8 ].…”

Section: Introductionmentioning

confidence: 99%

Advances in Female Germ Cell Induction from Pluripotent Stem Cells

Gulimiheranmu

Wang

Zhou

2021

Stem Cells International

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Germ cells are capable of maintaining species continuity through passing genetic and epigenetic information across generations. Female germ cells mainly develop during the embryonic stage and pass through subsequent developmental stages including primordial germ cells, oogonia, and oocyte. However, due to the limitation of using early human embryos as in vivo research model, in vitro research models are needed to reveal the early developmental process and related mechanisms of female germ cells. After birth, the number of follicles gradually decreases with age. Various conditions which damage ovarian functions would cause premature ovarian failure. Alternative treatments to solve these problems need to be investigated. Germ cell differentiation from pluripotent stem cells in vitro can simulate early embryonic development of female germ cells and clarify unresolved issues during the development process. In addition, pluripotent stem cells could potentially provide promising applications for female fertility preservation after proper in vitro differentiation. Mouse female germ cells have been successfully reconstructed in vitro and delivered to live offspring. However, the derivation of functional human female germ cells has not been fully achieved due to technical limitations and ethical issues. To provide an updated and comprehensive information, this review centers on the major studies on the differentiation of mouse and human female germ cells from pluripotent stem cells and provides references to further studies of developmental mechanisms and potential therapeutic applications of female germ cells.

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Pluripotent Cell Models for Gonadal Research

Cited by 8 publications

References 136 publications

Oligogenic Origin of Differences of Sex Development in Humans

Oligogenic Origin of Differences of Sex Development in Humans

Generation of a human ovarian granulosa cell model from induced pluripotent stem cells

Advances in Female Germ Cell Induction from Pluripotent Stem Cells

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