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Molecular Characterization of Pluripotency in Embryos and Embryonic Stem Cells

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Molecular Characterization of Pluripotency in Embryos and Embryonic Stem Cells Molecular characterization of pluripotency in embryos and embryonic stem cells Memòria presentada per Josep Pareja Gómez per a optar al grau de doctor pel Departament de Ciències de la Salut i de la Vida de la Universitat Pompeu Fabra Tesis dirigida per el Dr. Nikica Zaninovic i la Dra. Anna Veiga Universitat Pompeu Fabra Dr. Nikica Zaninovic Dra. Anna Veiga Josep Pareja Gómez Director Directora Doctorand Between the fifth and the tenth day the lump stem cells differentiates into the overall building plan of the embryo and its organs. It is a bit like a lump of iron turning into the space shuttle. In fact it is the profoundest wonder we can still imagine and accept, and at the same time so usual that we have to force ourselves to wonder about the wondrousness of this wonder. Miroslav Holub. “Another brick in the wall” Tesi Villanueva ambiguously quoting Pink Floyd 1 Agraïments / Agradecimientos / Aknowledgements 2 Aquesta tesi ha costat déu i ajuda, però com que jo sóc ateu, intentaré enumerar l'ajuda: totes les persones que han fet possible que finalment aquest treball vegi la llum. Però són tantes, que per escriure aquests agraïments podria trigar gairebé tant com he trigat a escriure el que ve després. First, I would like to thank Dr. Zev Rosenwaks and my PhD advisor at the CRMI, Dr. Nikica Zaninovic for his generosity and support. My gratitude for allowing me to fulfill my scientific curiosity granting me the support to do it in, undoubtedly, the best embryology lab of the world. Thanks Nikica for encouraging me to always go scientifically a step further of what I had ever possibly imagined . Estic en deute amb a la Dra. Anna Veiga per la seva contribució fonamental (en el sentit més estricte de la paraula) a que aquesta tesi sigui una realitat. Primer recolzant-me en tot moment en demanar la beca Fulbright (amb tota la paperassa que va haver de fer), però sobretot, després per el seu suport científic (i moral) en la configuració d'aquest manuscrit quan estava una mica perdut. Anna: moltes, moltes gràcies, per la teva generositat i la teva experiència científica i no científica. Gracias a la fundación Fulbright por haber financiado parte de mi estancia en el CRMI. Thanks to Lucinda Veeck-Gosden and Dr. Roger Gosden at the CRMI for opening the doors of the Embryology Lab for me. Thanks to Dr. Shahin Rafii for the generosity of letting me into his lab to see how cutting-edge science is cooked. Thanks to Dr. Daylon James for the patience of teaching me how to do stuff! I would like to thank to Dr. Jiying Hao, for her generosity and for contributing decisively with her effort to this research. Mirant retrospectivament, també vull agrair al Dr. Baldo Oliva haver confiat en mi alhora de configurar el seu grup al GRIB. La meva estada al SBL va ser l'inici de la meva formació com a científic i, al final, saber bioinformàtica ha estat fonamental per desenvolupar part del treball d'aquesta tesi. I encara mirant més retrospectivament, gràcies a l'amic (Dr.) Gabriel Gil per ser el primer que va mostrar-me el bon camí! Ja saps que em distrec fàcilment!!! 3 Gràcies a la Fina Gómez (Fingom!) per ser com ets, per haver-me ensenyat tantes coses tant a dintre del laboratori com a fora, per la teva generositat personal i la teva amistat. Estic en deute amb tu. Grazie a gli amici italiani: Fulvia Livralon ed il Dottore Massimo Ciaponi, grazie da vero per la vostra amicizia. Gràcies a la gent de Dexeus: A la Montse Boada,a la Bego, a la Itziar i la Mª José i les altres embriòlogues per ensenyar-nos als màsters el seu savoir-faire dins el laboratori d'embriologia. Thanks to everyone in the embryology lab at the CRMI: thanks to Elisabeth, Dina, Chris, Rich, June, Carol, Jason and Margarita because I can't imagine the lab without you. Thanks to Hong for her kindness and her permanent smile. Thanks to Anaya, for being always helpful and a great company. Thanks to Bob Clarke and Rosemary Berrios for their humanity and for being ready to help whenever they were needed. Thanks to Marco Toschi, for his companionship and understanding of what being a legal alien in New York is. Thanks to Evangeline Iwu, because despite being a pain to her with all my demands, she made me feel like her golden boy: you're my golden girl. Thanks for your friendship. A special, extra-extra-large (very very extra large) thanks to my dear friend Myriam Jackson: you're right, the lab wouldn't work without you! Myriam, gracias por su amistad, el cariño que me dio (y me da), por considerarme su darling, y sobretodo por su sentido del humor que nos hace tan felices. No se imagina cuánto la echo de menos. Thanks to my dear friend Naomi Lourie, for the long talks -eating popcorn- when everybody had left the lab (exept for LV) and for making me feel close to her in the middle of the ups and downs of the big city. I miss you. Gràcies a tots els meus amics i amigues de la vella guàrdia del GRIB! Gràcies al Pep Abril, a l'Òscar i a l'Alfons, per la seva paciència y generositat amb aquest pobre usuari. Gràcies a la Montse (la Barbany) per la seva amistat i per compartir amb mi barracons, linux, i algoritmes! Ets un exemple de passió científica i de passió maternal! Gràcies a en Fabien per ser un model de perseverància i un amic. Gràcies a en Robert per la seva proximitat, bonhomia i amistat. Gràcies a en Loris i la Meritxell, els kamikazes més apassionats que conec i uns grans amics. Gràcies a la Rut per haver-me deixat veure-la de ben a propet, per tots els matins asseguts mirant despuntar el sol davant el mar amb un te i la seva companyia, i per la seva amistat. Gracias a Cristina Dezi, por su inagotable capacidad de dar amor, por haberme dejado ser su abrazador oficial y amigo suyo. Te echo de menos!!! A Eduardo por ser el amigo con el mejor cuerpo de todos los que tengo... y de 4 corazón más grande también. A en Genís per ensenyar-me a menjar xampinyons crus, i per deixar- se apropar vencent la por i regalar-me la seva amistat. Thanks to Noura, for sharing her wit, her irony and joy with us, and for her friendship. A Natalia, por ese cariño a flor de piel que tiene y la poesia que la envuelve. A la Bet, per ser l'amiga que ÉS permanentment, incondicional, generosa i per ser sempre a 3mm. A Ramón por ser modelo a seguir y amigo SIEMPRE, dando a manos llenas todo lo que tiene, y más. Gràcies als meus amics de Sabadell, els de tota la vida. A en Marcel per tots els moments d'amistat compartits quan érem tan inconscients i bèsties. A Dani por haber sido siempre referencia personal, por el cariño de una amistad de tantos años. A Virginia por haber sido apoyo incondicional en un momento confuso de mi vida, por desafiarme a que me pusiera camisetas de colores chillones, por su sabiduría y su amistad sincera. A Dani y Laura, a Jose y Marta, por su amistad y porque que cada reencuentro es una fiesta. A Xavi Aznar, por las afinidades y las neuras compartidas además de su amistad. A Carlos por las cosas desconocidas que decidimos compartir y por su amistad. A Ana Mari, por ser como es, por el cariño que me ha brindado siempre, pase lo que pase. Gracias a Clara, por ser la primera persona en demostrarme qué es la amistad sin condiciones, por ayudarme a ser mejor persona, y por los muchos buenos momentos compartidos durante tantos años. Gracias a mis niñas de Heidelberg. Ich wurde mich bei meiner liebsten Freundin Pepita (Esther Schindler) bedanken dafür, dass sie mich glücklich meine 3 Monaten in Heidelberg gemacht hat: Danke für deinen riesigen Herz, und entschuldige mich, denn ich habe nicht geschrieben so oft wie ich es mir gewünscht hätte. A Ana Paeffgen, por irradiar alegría, por regalarme su cariño el primer segundo después de conocernos en la Hauptstrasse y por brindarme su amistad desde ese instante. A Sílvia Díez, por los gloriosos momentos compartidos, y porque sin tí, tu cariño y amistad, probablemente esta tesis no se hubiese podido realizar. Gracias por ser la mejor sparring emocional del mundo. Os echo de menos! (Ich vermisse euch!). Gràcies als meus amics veterinaris, Marcel, Oscar, Maribel que m'han fet sentir com si jo també fos un d'ells. A l'Aida, perquè tot i no ser veterinària és referent en bricolatge, serenitat, bona conducció i carinyu. A l'Alhelí, per ser la veterinària més petita (i amb el cabell més estrany) però també la que te el cor més gros! Gràcies per la teva amistat. 5 Gràcies a en Jordi (Font) Hereu per la seva amistat des dels dies de l'Autònoma i per ser sempre tot cor i comprensió. Gràcies als tots els meus companys al Consorci Sant Gregori per haver-me fet sentir un més i haver- se'm apropat. També vull donar les gràcies a tots els usuaris amb els que he tractat, per ensenyar-me què és la humanitat. Gràcies a l'Ignasi per ser referent en eficàcia i eficiència (diferenciant el significat, hehe) i tantes altres coses i per la seva generositat sense límits i amistat sincera.
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