Carlos Simón, MD, PhD.Posdoctoral Investigator:
Jose V. Medrano, PhD.PhD Student:
Ana M. MartínezLab. Technician:
Reprogramación in vitro de células somáticas adultas humanas a células germinales
Infertility affects up to 15% of couples in reproductive age in Europe. Among the different diseases that can lead to infertility, poor gamete quality plays an important role and this is why there is an emerging demand on donated sperm and eggs in fertility clinics. The study of germ line development is necessary to understand poor gamete quality causes and design treatments to improve it. However, our current knowledge of this process in humans is little, mainly due to inaccessibility to early stages of development of human germ line development because of ethical impediments.
In this sense, the in vitro derivation of germ cells from adult somatic cells by genetic manipulation can lead to the establishment of an invaluable model for the study of the insights of human germ line development. Furthermore, knowledge obtained from this study can be a key to understand gamete-related diseases in order to improve their treatment. Finally, the development of non-integrative genetic manipulation techniques for the derivation of germ cells in vitro could convert them in clinical-grade gametes that allow patients to be the biological parents of their children without the need of donated gametes.
We based in previous reports from other groups that paved the way to achieve the correct transdifferentiation from on cell source to another different cell fate by genetic reprogramming. Thus, our goal is to achieve the successful in vitro reprogramming of human somatic cells to germ cells. These germ cells can be employed as an in vitro model to study the insights of hum germ line development, as well they can be used in the future as a source of gametes that allow patients with severe fertility impediments to generate functional gametes.
Figure 1. Schematic representation of the main events during mammalian germ line development.
Figure 2. Experimental design followed in this project.
1. Medrano JV, Pera RA, Simon C. Germ cell differentiation from pluripotent cells. Semin Reprod Med. 2013;31(1):14-23.
2. Medrano JV, Ramathal C, Nguyen HN, Simon C, Reijo Pera R. Divergent RNA-bindig proteins DAZL and VASA induce meiotic progression in human germ cells derived in vitro. Stem Cells. 2012; 30(3):441-51.
3. Panula S, Medrano JV, Kee K, Bergstrom R, Nguyen HN, Byers B, Wilson KD, Simon C, Hovatta O, Reijo Pera RA. Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells. Hum Mol Genet. 2011; 20(4):752-62
4. Medrano JV, Marqués-Marí AI, Aguilar CE, Riboldi M, Garrido N, Martínez-Romero A, Gil-Salom M, Simón C. Comparative analysis of the germ cell markers c-KIT, SSEA-1 and VASA in testicular biopsies from secretory versus obstructive azoospermia. Mol Hum Reprod. 2010; 16(11):811-17.
5. Aguilar C, Poo ME, Gomez E, Galan A, Sanchez E, Marques-Mari A, Ruiz V, Medrano J, Riboldi M, Enseñat-Waser R, Valbuena D, Simon C. Derivation, Characterization, Differentiation and Registration of Seven Human Embryonic Stem Cell Lines (VAL-3, -4, -5, -6M, -7, -8, and -9) on Human Feeder. In Vitro Cell Dev Biol Anim. 2009; 46(3-4):317-26.
6. Marques-Mari AI, Lacham-Kaplan O, Medrano JV, Simon C. Differentiation of Germ Cells and Gametes from Stem Cells. Hum Reprod Update. 2009; 1: 1–12.
Published book chapters
1. Medrano JV, Simon C, Reijo Pera R. Human germ cell differentiation from pluripotent embryonic stem cells and induced pluripotent stem cells. In Wassarman and Rosenwaks (ed.), Human fertility: Methods and protocols. Humana press. In press.
2. Medrano JV, Marqués-Marí AI, Simon C. Germline Differentiation From Stem Cells. In Sook-Cheng LIM (ed.), Stem cells: from bench to the bedside, 2nd edition. World Scientific publishing. 2010; 557-582.
3. Marques-Mari AI, Medrano JV, Simon C. Differentiating Gametes from Stem Cells. In H. Baharvand (ed.), Trends in Stem Cell Biology and Technology. Humana press. 2009; 137-147.