We are studying the molecular basis of cellular heterogeneity.
Cellular heterogeneity is a widespread phenomenon that affects every organism in every biological population, thereby making all individuals unique. This phenomenon also has important physio-pathological implications.
Apoptosis in cell sub-groups after the administration of chemotherapy treatments to cancer patients is a good example of how cellular heterogeneity can be created. The cells that survive these treatments often regenerate to form tumors that are more aggressive than the one that originally gave rise to them. Indeed, this is the main cause of tumor relapse.
Cell differentiation is also an important mechanism driving the creation of variability. In this sense, stem cell fate is governed by the stochastic segregation of molecular and/or cellular components.
We have identified another important source of cellular variability: the asymmetrical and stochastic segregation of mitochondria during mitotic cell divisions. The uneven partition of mitochondria creates metabolically dissimilar cells, which results in gene expression noise and phenotype heterogeneity.
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Our scientific contributions
Mitochondrial levels determine variability in cell death by modulating apoptotic gene expression.
Márquez-Jurado S, Díaz-Colunga J, das Neves RP, Martinez-Lorente A, Almazán F, Guantes R and Iborra FJ
Nature Communications, 2018 Jan,  DOI:  10.1038/s41467-017-02787-4,  Vol. 9,  pag. 389-389
Mitochondria and the non-genetic origins of cell-to-cell variability: More is different.
Guantes R, Díaz-Colunga J and Iborra FJ
BIOESSAYS, 2016 Jan,  DOI:  10.1002/bies.201500082,  Vol. 38,  pag. 64-76
Global variability in gene expression and alternative splicing is modulated by mitochondrial content.
Guantes R, Rastrojo A, Neves R, Lima A, Aguado B and Iborra FJ
GENOME RESEARCH, 2015 May,  DOI:  10.1101/gr.178426.114,  Vol. 25,  pag. 633-644
Mitochondrial variability as a source of extrinsic cellular noise.
Johnston IG, Gaal B, Neves RP, Enver T, Iborra FJ and Jones NS
PLoS Computational Biology, 2012 Mar,  DOI:  10.1371/journal.pcbi.1002416,  Vol. 8,  pag.
Connecting variability in global transcription rate to mitochondrial variability.
das Neves RP, Jones NS, Andreu L, Gupta R, Enver T and Iborra FJ
PLOS BIOLOGY, 2010 Dec,  DOI:  10.1371/journal.pbio.1000560,  Vol. 8,  pag.