Laboratory Juliane Glaser

Transposable elements in mammalian development

Our lab is interested in the epigenetic mechanisms that govern mammalian embryonic development. Our main focus is on transposable elements (TEs) and how those genetic parasites contribute to both pathologic and healthy developmental phenotypes. 

About half of the human genome is made of TEs. Many have been co-opted as cis-regulatory elements, non-coding RNA or protein products driving physiological functions. Yet, their mobile nature makes TEs a source of insertional mutations, affecting gene expression and cellular processes. Epigenetic silencing mechanisms safeguard the genome from these detrimental effects. The lab aim to understand how variation in the epigenome of TEs results in molecular and morphological phenotypes during embryonic development.

Mission

We are fascinated by the mechanisms of TEs interacting with gene regulation and influencing cell state. Very little is known about how this can be applied to cell differentiation and organogenesis during mammalian development. Using in vitro and in vivo mouse models, we investigate the genetic and morphogenetic events modulated by TE insertion during development.

Goals

Our lab aims to achieve the following goals to decipher how TEs contribute to mammalian embryo formation: 

  • Characterize new mechanisms by which the epigenetic de-repression of TEs leads to congenital disease.
  • Explore the role of TEs during lineage commitment and tissue shaping.
  • Decipher how cell-specific expression of TEs in the embryo is influenced by genomic regulation and the gene regulatory landscape.
  • Develop new tools to systematically test the impact of TE insertion on developmental cell type and gene regulation.

Approach

Our lab’s main approach is based on genome engineering in mouse embryonic stem cells and generation of transgenic mouse models, followed by molecular and morphological dissection of developmental phenotypes. We employ CRISPR/Cas9 technology to generate tailored stem cell and in vivo mouse models targeting specific TEs or for genome-wide screening. We combine this with high-throughput sequencing (including single-cell and long-read sequencing technologies) and imaging of mouse embryos. 

Impact

The formation of a functional embryo is precisely regulated by genetic and morphogenetic events. Our research aim to provide novel insight into unexplored areas of (epi)genomic regulation during development, bringing TEs as as an important player in genetic unsolved congenital malformation and physiological embryogenesis. Our findings on mouse models will directly impact the understanding of mammalian development with a link to disease phenotype that we will apply to humans genomic datasets.


Selected Publications

Glaser J*, Cova G, Fauler B, Prada-Medina CA, Stanislas V, Phan MQH, Schöpflin R, Aktas Y, Franke M, Andrey G, Paliou C, Laupert V, Chan WL, Wittler L, Mielke T, Mundlos S* (2024)
Enhancer adoption by an LTR retrotransposon generates viral-like particles causing developmental limb phenotypes
bioRxiv 2024.09.13.612906.

* co-corresponding authors
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 (2023)
Combinatorial effects on gene expression at the Lbx1/Fgf8 locus resolve split-hand/foot malformation type 3
Nature Communications 14(1), 1475.

* co-first authors
Glaser J, Iranzo J, Borensztein M, Marinucci M, Gualtieri A, Jouhanneau C, Teissandier A, Gaston-Massuet C, Bourc'his D (2022)
The imprinted Zdbf2 gene finely tunes control of feeding and growth in neonates
Elife 11, e65641.
Glaser J, Mundlos S (2022)
3D or Not 3D: Shaping the Genome during Development
Cold Spring Harbor Perspectives in Biology 14(5), a040188. 
Greenberg MV*, Glaser J*, Borsos M, Marjou FE, Walter M, Teissandier A, Bourc'his D (2017)
Transient transcription in the early embryo sets an epigenetic state that programs postnatal growth
Nature Genetics 49(1), 110-118.

* co-first authors
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