Borja Gomez Ramos (Luxembourg)
University of Luxembourg
Department of Life Sciences and Medicine
Borja Gómez Ramos is a PhD candidate at the University of Luxembourg, with dual affiliation to DLSM and LCSB. His work focuses on iPSC technology and its differentiation into relevant CNS cell types. He is studying the transcriptional and epigenetic changes during dopaminergic neuron differentiation to identify novel transcription factors driving this process using state-of-the-art omics data integration approaches. Previously, he studied an M.Sc in Molecular Medicine at Georg-August-Universität Göttingen, a B.Sc. in Biochemistry and Molecular Biology at the University Rovira i Virgili and another B.Sc. in Applied Bioscience at the University of the West of Scotland. Borja´s professional interests are neurodegeneration and translational research.

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 Conference Calendar

INTEGRATED GENOMICS FOR THE IDENTIFICATION OF NOVEL FACTORS CONTROLLING MIDBRAIN DOPAMINERGIC NEURON DIFFERENTIATION

Session Name
0230 - SINGLE-CELL GENOMICS STEM CELLS 2 (ID 198)
Session Type
SYMPOSIUM
Date
Wed, 16.03.2022
Session Time
08:30 AM - 10:30 AM
Room
ONSITE: 131-132
Lecture Time
08:30 AM - 08:45 AM
Presenter

Abstract

Aims

Objective: In this project, we are studying the gene regulatory program underlying midbrain dopaminergic neurons (mDANs) to identify novel factors controlling their lineage commitment with the aim to facilitate improved mDAN reprogramming in the future.

Methods

Methods: Using human induced pluripotent stem cell (hiPSC) technology and a tyrosine hydroxylase reporter cell line, we have generated time-series data on chromatin accessibility and transcriptome changes during neural precursor differentiation towards mDANs. Integration of the transcription factor (TF) binding profiles with the corresponding transcriptome data across differentiation time points was performed using our EPIC-DREM pipeline. The generated time-point-specific gene regulatory networks were used to identify putative key TFs controlling mDAN differentiation. To further prioritize the identified TFs, we performed low input ChIP-seq for histone H3 lysine 27 acetylation (H3K27ac) to identify TFs controlled by super-enhancers in mDANs.

Results

Results: LBX1, NHLH1 and NR2F1/2 were identified as novel factors and selected for functional validation. RNAi assays showed the selected TFs to be essential for mDAN differentiation. Transcriptome profiling upon TF depletion was performed to characterize the main pathways and targets of each candidate in this process.

Conclusions

Conclusions: First, our data set provides an integrated multi-omic profile of iPSC-derived mDANs. Second, our integrative analysis identified novel TFs controlling mDAN differentiation and predictions were validated in vitro. Third, our results could be exploited to improve in vitro protocols. Lastly, the candidates identified have been found to be deregulated in iPSC from Parkinson’s disease (PD) patients. Therefore, our results could also be used to better understand PD pathological mechanisms.

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