Life Sciences Research for Lifelong Health

Myriam Hemberger

Myriam Hemberger has located to Canada to take up a Professorship at the University of Calgary. Her new webpage can be found here.

Research Summary

The focus of our work is on the establishment, maintenance and differentiation of trophoblast cells leading to formation of a functional placenta. The placenta is the defining organ of most mammals, providing a nutritive conduit that is crucial for all embryonic development to occur. Trophoblast cells are the major building blocks of the developing placenta. They are the first cell type to arise very early in development when they are set apart from cells giving rise to the embryo itself. The various functions of trophoblast cells early in development are vital for reproductive success, as they lay the foundations for a normal pregnancy and healthy foetus later on. A better understanding of the mechanisms underlying these early events will be critical to develop better screens and therapeutic avenues for pregnancy complications.
 
We are in particular interested in how the early trophoblast niche is regulated by transcription factors and specific epigenetic modifiers to ensure normal development. Leading on from this, we also investigate how susceptible the trophoblast compartment is to perturbations by extrinsic factors that activate specific signalling cascades, including in the context of development in mothers of advanced age. For this we are taking a range of high-throughput epigenomic and transcriptomic approaches to study these early events in placental development.
 
Key among our tools is the use of murine trophoblast stem (TS) cells, which mimic many of the properties of the early placenta. Learning about the self-renewal mechanisms of TS cells, in comparison to embryonic stem (ES) cells, will help us uncover the fundamental principles of how the early placenta develops and is influenced by external factors, which may be predictive for life long physiology and health. These insights will also enable us to better understand the earliest steps in human placentation and to develop novel cellular research tools to study the underlying molecular processes.

Latest Publications

Mechanisms of early placental development in mouse and humans.
Hemberger M, Hanna CW, Dean W

The importance of the placenta in supporting mammalian development has long been recognized, but our knowledge of the molecular, genetic and epigenetic requirements that underpin normal placentation has remained remarkably under-appreciated. Both the in vivo mouse model and in vitro-derived murine trophoblast stem cells have been invaluable research tools for gaining insights into these aspects of placental development and function, with recent studies starting to reshape our view of how a unique epigenetic environment contributes to trophoblast differentiation and placenta formation. These advances, together with recent successes in deriving human trophoblast stem cells, open up new and exciting prospects in basic and clinical settings that will help deepen our understanding of placental development and associated disorders of pregnancy.

+ View Abstract

Nature reviews. Genetics, , 1471-0064, , 2019

PMID: 31534202

ZFP57 regulation of transposable elements and gene expression within and beyond imprinted domains.
Shi H, Strogantsev R, Takahashi N, Kazachenka A, Lorincz MC, Hemberger M, Ferguson-Smith AC

KRAB zinc finger proteins (KZFPs) represent one of the largest families of DNA-binding proteins in vertebrate genomes and appear to have evolved to silence transposable elements (TEs) including endogenous retroviruses through sequence-specific targeting of repressive chromatin states. ZFP57 is required to maintain the post-fertilization DNA methylation memory of parental origin at genomic imprints. Here we conduct RNA-seq and ChIP-seq analyses in normal and ZFP57 mutant mouse ES cells to understand the relative importance of ZFP57 at imprints, unique and repetitive regions of the genome.

+ View Abstract

Epigenetics & chromatin, 12, 1756-8935, 49, 2019

PMID: 31399135

Common and distinct transcriptional signatures of mammalian embryonic lethality.
Collins JE, White RJ, Staudt N, Sealy IM, Packham I, Wali N, Tudor C, Mazzeo C, Green A, Siragher E, Ryder E, White JK, Papatheodoru I, Tang A, Füllgrabe A, Billis K, Geyer SH, Weninger WJ, Galli A, Hemberger M, Stemple DL, Robertson E, Smith JC, Mohun T, Adams DJ, Busch-Nentwich EM

The Deciphering the Mechanisms of Developmental Disorders programme has analysed the morphological and molecular phenotypes of embryonic and perinatal lethal mouse mutant lines in order to investigate the causes of embryonic lethality. Here we show that individual whole-embryo RNA-seq of 73 mouse mutant lines (>1000 transcriptomes) identifies transcriptional events underlying embryonic lethality and associates previously uncharacterised genes with specific pathways and tissues. For example, our data suggest that Hmgxb3 is involved in DNA-damage repair and cell-cycle regulation. Further, we separate embryonic delay signatures from mutant line-specific transcriptional changes by developing a baseline mRNA expression catalogue of wild-type mice during early embryogenesis (4-36 somites). Analysis of transcription outside coding sequence identifies deregulation of repetitive elements in Morc2a mutants and a gene involved in gene-specific splicing. Collectively, this work provides a large scale resource to further our understanding of early embryonic developmental disorders.

+ View Abstract

Nature communications, 10, 2041-1723, 2792, 2019

PMID: 31243271

 

Group Members

Latest Publications

Mechanisms of early placental development in mouse and humans.

Hemberger M, Hanna CW, Dean W

Nature reviews. Genetics
1471-0064: (2019)

PMID: 31534202

ZFP57 regulation of transposable elements and gene expression within and beyond imprinted domains.

Shi H, Strogantsev R, Takahashi N

Epigenetics & chromatin
12 1756-8935:49 (2019)

PMID: 31399135

Common and distinct transcriptional signatures of mammalian embryonic lethality.

Collins JE, White RJ, Staudt N

Nature communications
10 2041-1723:2792 (2019)

PMID: 31243271

Inhibition of Phosphoinositide-3-Kinase Signaling Promotes the Stem Cell State of Trophoblast.

Lee CQE, Bailey A, Lopez-Tello J

Stem cells (Dayton, Ohio)
37 1549-4918:1307-1318 (2019)

PMID: 31233251

Regulation of Placental Development and Its Impact on Fetal Growth-New Insights From Mouse Models.

Woods L, Perez-Garcia V, Hemberger M

Frontiers in endocrinology
9 1664-2392:570 (2018)

PMID: 30319550

Divergent wiring of repressive and active chromatin interactions between mouse embryonic and trophoblast lineages.

Schoenfelder S, Mifsud B, Senner CE

Nature communications
9 2041-1723:4189 (2018)

PMID: 30305613

A Critical Role of TET1/2 Proteins in Cell-Cycle Progression of Trophoblast Stem Cells.

Chrysanthou S, Senner CE, Woods L

Stem cell reports
2213-6711: (2018)

PMID: 29576538

Integrin α2 marks a niche of trophoblast progenitor cells in first trimester human placenta

Lee CQE, Turco M, Gardner L

Development (Cambridge, England)
1477-9129: (2018)

PMID: 29540503

Placentation defects are highly prevalent in embryonic lethal mouse mutants.

Perez-Garcia V, Fineberg E, Wilson R

Nature
1476-4687: (2018)

PMID: 29539633