Felipe VILELLA (Spain)
Prof. Felipe Vilella was graduated in Biological Sciences (2002) and Biochemistry (2004) at the University of Navarra. In 2006, I obtained my PhD in Molecular Biology at the Faculty of Medicine of the University of Lleida with the highest degree "Cum Laude". He did the first postdoctoral fellowship in the laboratory of Professor Aragon in the Clinical Science Centre of the Medical Research Council (MRC) in London supported by the Marie Curie program. In 2007, he was awarded the prestigious scholarship from the Ministry of Education and Science (FECYT) for the formation of Spanish doctors abroad. During his years in England (2006-2009), he specialized in the mechanisms of DNA repair and progression in the cell cycle of eukaryotic cells. This knowledge gave him the opportunity to make a second post-doctoral fellow in the laboratory of Professor Lako in a mixed unit created between the University of Newcastle and the Prince Felipe Research Center in Valencia (CIPF). During this time, he moved my knowledge of cell biology to embryonic stem cells and its application in the field of regenerative medicine. In 2011, he began my career as principal investigator of the Endometrial Receptivity laboratory within the IVI Foundation directed by Professor Simon. His field of work is focused on the study of endometrial receptivity and the cross-talk between the mother and the embryo during implantation. In 2014, he obtained a Miguel Servet position issued by the Institute of Health Carlos III and became part of the Foundation for Research of the Clinical Hospital of Valencia (INCLIVA).
Prof. Felipe Vilella has published 36 scientific works in prestigious journals such as Nature Cell Biology, Stem Cells, Endocrine Reviews, Development and Science among others, and he is a regular contributor and reviewer of international journals. He has directed 3 doctoral theses. He has participated in over 17 international projects so far, being principal investigator in 7 of them. He has participated as invited speaker in over 65 international conferences.
Abstract
Single Cell RNAseq Provides a Molecular and Cellular Cartography of Changes to the Human Endometrium Through the Menstrual Cycle
Objective:
Despite its relevance, mechanistic understanding of the human endometrium remains rudimentary. We characterized the transcriptomic transformation of human endometrium at single cell resolution, dissecting multidimensional cellular heterogeneity across the entire natural menstrual cycle.
Design:
Single cell RNAseq (scRNAseq) was performed in 2,149 endometrial single cells obtained after separation of 19 endometrial biopsies across the natural cycle presenting a high resolution endometrial transcriptomic map decoupled in cell types and cell states.
Materials and Methods:
After tissue dissociation, single cell capture, mRNA reverse-transcription, and cDNA amplification were performed on the Fluidigm C1 system using default scripts for mRNA Seq. All capture site images were recorded using an in-house built microscopic system. For quality filtering, fraction of reads mapped to ERCC (
) was used as the quality metric and empty capture sites on the C1 chip as the null model through which 2,149 single cells were retained for downstream analysis (
< 0.05).
Results:
Single cell analysis by dimensional reduction via t-distributed stochastic neighbor embedding (tSNE) revealed that human endometrium consists of six cell types that are not time-associated across the menstrual cycle. Canonical markers and highly differentially expressed genes enabled identification of differential cell types: stroma, endothelium, macrophage, and lymphocyte, ciliated epithelium and unciliated epithelium. Investigation time variable as an informative proxy revealed that endometrial transformation consists of four major phases across the menstrual cycle. The window of implantation (WOI) opens with an abrupt and discontinuous transcriptomic activation in unciliated epithelium with major genes PAEP, GPX3, and CXCL14 governing this function. Transcriptomic dynamics in stroma cells demonstrated more stage-wise characteristics, where genes up-regulated include DKK1, S100A4, and CRYAB although the transition was not as abrupt as in their epithelial counterparts. Also, transcriptome signatures in deviating glandular and luminal epithelium supports a mechanism for adult epithelial gland formation. Lastly, we provided evidence for the direct interplay between stroma and lymphocytes during decidualization, stromal cells are directly responsible for the activation of lymphocytes through IL2-eliciated pathways.
Conclusion:
Our unbiased single cell analysis framework allows for the definition of global feature of endometrial transcriptomic dynamics as a step forward to the classical histological definition of the human menstrual cycle. Our results reveal unique molecular characteristics of transitions between non-receptive and receptive endometrial state, as well as insights in mechanistic understanding in the relationship between cell remodeling, proliferation, and differentiation during endometrial homeostasis.