- Research lines
1.
Somatic cell reprogramming analysis. Identification of new factors and analysis of pathways involved in the process.
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Using the oocyte as source of information for iPSC reprogramming
Induced pluripotent stem cells (iPSCs) were generated from human somatic cells for the first time in 2007 by two laboratories simultaneously, Prof. S. Yamanaka and Prof. J. Thomson, showing human fibroblasts transformation to pluripotent cells (iPSCs) through ectopic expression of four transcription factors (OCT4, SOX2, KLF4 and c-Myc or OCT4, SOX2, NANOG and LIN28 respectively).
Although theoretically this is a “simple” protocol, cellular reprogramming is still a very inefficient process and more importantly, the molecular mechanisms governing the transformation of a somatic cell into an iPSC are still not completely understood.
The process by which a somatic cell acquires a pluripotent state is an epigenetic phenomenon, we and others study the specific molecular mechanisms involved. The evidence provided by our research supports the idea that studying the genes and gene products present in the oocyte (more specifically the unfertilized metaphase II oocyte) can help us understanding how pluripotency is acquired in somatic cells.
© Elena González
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Explore reprogramming and regenerative characteristic of stromal cell types
Cell reprogramming depends among other factors on the somatic cell of origin. In our group we study the molecular characteristics that determine cell identity, as well as its tendency or efficiency for transformation into other cell types, both through dedifferentiation to a pluripotent state and through direct transdifferentiation. We have characterized menstrual blood-derived stromal cells (MenSCs) as a reprogramming-prone cell type with other regenerative properties that are being explored.
© Elena González. Illustration taken from Sanchez-Mata A. and González-Muñoz E. iSCIENCE (2021) DOI: 10.1016/j.isci.2021.103501
2.
Disease in a dish. Use of cell reprogramming for disease modeling
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Disease in a dish
Induced pluripotent stem cells (iPSCs) use is particularly useful for the study of rare diseases, specifically in neurodegenerative diseases. Nervous tissue samples from patients are rarely accessible and animal models, often do not recapitulate all characteristic of the disease.
The discovery that somatic cells from patients affected by neurological disorder can be reprogrammed to a pluripotent state (iPS cells), and once reprogrammed, these cells can expand and differentiate into specific populations of neurons, and more recently the generation of brain organoids, opened a promising field for research and understanding the molecular and cellular basis of these abnormalities and the development of specific drugs.
Our short term goal is to generate iPSCs and specific cell types affected in different neuropathies such as Ataxias, multiple sclerosis, West syndrome and Huntington disease among others, and to develop in vitro models in which perform functional assays to uncover altered cellular pathways that may explain the origin of the specific pathological states. Through scientific collaborations we aim to uncover new pathway and targets that may enable the development of treatment alternatives.
© Elena González. Created with BioRender.com
Our research is funded by competitive grants from:
