Research:
Our lab studies how transposable elements (TEs) contribute to mammalian embryonic development in health and disease. Half of the mammalian genome is composed of TEs, whose expression is controlled by epigenetic mechanisms. While TE activity is shown to influence the early mammalian embryo and adult pathologies, its role in the crucial phase of lineage commitment and organogenesis during development is unclear. We use in vitro and in vivo mouse embryonic models (cells, organoids and embryos), combined with genome editing tools, sequencing and imaging to tackle this phenomenon. Our main focuses are to understand 1) how TEs control physiological function, such as lineage commitment and organ formation, 2) what are the mechanisms by which TEs cause congenital pathologies, and 3) what protects the genome from the detrimental effects of TEs during development.
Keywords:
embryonic development, epigenetics, retrotransposons, endogenous retroviruses, gene regulation.
Selected publications:
Comparative single-cell analyses reveal evolutionary repurposing of a conserved gene programme in bat wing development.
Schindler M, Feregrino C, Aldrovandi S, Lo B-W, Monaco AA, Ringel AR, Morales A, Zehnder T, Behncke RY, Glaser J, Barclay A, Andrey G, Kragesteen BK, Hagerling R, Haas SA, Vingron M, Ulitsky I, Marti-Renom M, Hechavarria JC, Fasel NJ, Hiller M, Lupianez D, Mundlos S, Real FM. Nature Ecology & Evolution. 2024
Enhancer adoption by an LTR retrotransposon generates viral-like particles causing developmental limb phenotypes.
Glaser J#, Cova G, Faulner B, Prada-Medina CA, Stanislas V, Phan MHQ, Schöpflin R, Laupert V, Aktas Y, Andrey G, Franke M, Paliou C, Chan W, Wittler L, Mielke T, Mundlos S#. Nature Genetics. 2024
STIGMA: Single-cell tissue-specific gene prioritization using machine learning.
Balachandran S, Prada-Medina CA, Mensah MA, Glaser J, Kakar N, Nagel I, Pozojevic J, Audain E, Hitz MP, Kircher M, Sreenivasan VKA, Spielmann M. The American Journal of Human Genetics. 2024
Combinatorial effects on gene expression at the Lbx1/Fgf8 locus resolve Split-Hand/Foot Malformation type 3.
Cova G*, Glaser J*, Schöpflin R, Prada-Medina CA, Ali S, Franke M, Falcone R, Federer M, Ponzi E, Ficarella R, Novara F, Wittler L, Timmermann B, Gentile M, Zuffardi O, Spielmann M, Mundlos S. Nature Communications. 2023
Repression and 3D-restructuring resolves regulatory conflicts in evolutionarily rearranged genome.
Ringel AR, Szabo Q, Chiariello AM, Chudzik K, Schöpflin R, Rothe P, Mattei AL, Zehnder T, Harnett D, Laupert V, Bianco S, Hetzel S, Glaser J, Phan MHQ, Schindler M, Ibrahim DM, Paliou C, Esposito A, Prada-Medina CA, Haas SA, Giere P, Vingron M, Wittler L, Meissner A, Nicodemi M, Cavalli G, Bantignies F, Mundlos S, Robson MIR. Cell. 2022
The imprinted Zdbf2 gene finely tunes control of feeding and growth in neonates.
Glaser J, Iranzo J, Marinucci M, Borenztein M, Gualtieri A, Jouhanneau C, Teissandier A, Gaston Massuet C, Bourc’his D. eLife. 2022
Transient transcription in the early embryo sets an epigenetic state that programs postnatal growth.
Greenberg MVC*, Glaser J*, Borsos M, El Marjou F, Walter M, Teissandier A, Bourc’his D. Nature Genetics. 2017
A discrete transition zone organizes the topological and regulatory autonomy of the adjacent Tfap2c and Bmp7 genes.
Tsujimura T, Klein FA, Langenfeld K, Glaser J, Huber W, Spitz F. PLoS Genetics. 2015
3D or Not 3D: Shaping the Genome during Development.
Glaser J, Mundlos S. Cold Spring Harbor Perspectives in Biology. 2021
Genomic imprinting and physiological processes in mammals.
Tucci V, Bartolomei MS, Benvenisty N, Bourc’his D, Charalambous M, Dulac C, Feil R, Glaser J, Huelsmann L, John R, McNamara G, Moorwood K, Muscatelli F, Sasaki H, Strassmann BI, Vincenz C, Wilkins J, Isles A, Kelsey G, Ferguson-Smith AC. Cell. 2019