From single cells to systemic change: shining a light on poorly understood aspects of women’s health

Thank you! In my group, we look at how various tissues in the body form and function, with a particular emphasis on tissues that act as barriers, connecting with the external environment. We are deciphering the intricate communication processes that enable cells to come together and form these barrier tissues, many of which are rich in immune cells.

One of our most exciting areas of study centres around the uterus. During pregnancy, the uterine lining undergoes a remarkable transformation into the placenta, a complex organ that facilitates the exchange of nutrients and waste between the mother and the growing foetus. The uterus undergoes significant changes in structure, blood supply, and hormonal responsiveness to support the developing embryo and ensure a successful pregnancy. Striking the right balance between allowing implantation and gestation of the embryo while safeguarding against infections to the mother requires highly intricate immune mechanisms.

Outside of pregnancy too, the uterus is an incredibly unique part of the female body. No other tissue perfectly breaks down and regenerates every single month - around 400 times in the average woman’s lifetime. It also leaves no scarring whatsoever, vanishing without a trace. We as researchers, and not just those working in women’s health, have lots to learn about the remarkable regeneration of this tissue.

There are many human-specific features of the uterus, so we have had to innovate new ways to understand this very inaccessible tissue.

We use single-cell technologies to sequence the mRNA of each individual cell found in the tissue and then apply spatial transcriptomic technologies to see where exactly different cell types are located in our tissues and the cell-cell interactions – how they work together. This forms a ‘screenshot’ of the tissues.

While these ‘screenshot’ images of tissues are great, we realised we lacked a more dynamic view of the tissues. That is why we have been using human organoids – three-dimensional mini tissue cultures derived from stem cells – able to mimic the structural and the functional properties of the in vivo tissue.

Organoids give us a controlled environment where we can then make perturbations - alterations - and analyse their effect on the organoid. There are two major strands to this. One is to alter the microenvironment of the organoid tissue – changing molecules or reagents within the medium, or adding drugs – that interferes with a certain pathway, for example that could be involved in treating endometriosis. The other way is through gene editing tools to alter a specific gene or regulatory region. These perturbations allow us to investigate disease mechanisms, test potential therapies and move towards the ultimate goal of personalised medicine.

Freddy Wong, Staff Scientist in Roser's team, working in Cellular Genetics laboratories

The uterus has a vital impact on reproduction and women’s health. Despite this, common conditions affecting women like endometriosis, where endometrial-like tissue grows outside of the uterus, receive little funding and is poorly studied. One in ten women experience endometriosis (1), with debilitating symptoms, but in this country it takes an average of seven years (2) to receive a diagnosis. A recent piece in Nature (3) highlights the extent of underfunding across women’s health research. This serves as a strong motivation for our team to be working on a topic that actively addresses this problem.

It is also a great technical challenge to study! The complexity and monthly regeneration of the tissue mean we generate large amounts of data, but here at the Sanger Institute we are lucky to be able to develop tools to make sense of these healthy reference datasets. There is still a lot of room for improvement in organoids to truly mimic the complexity and make smarter perturbations, but our findings from single-cell, computational, and in vitro approaches strengthen each other.

One thing you need to know about my group is that we are multidisciplinary and multicultural. We are made up of molecular biologists, immunologists, developmental biologists and computational scientists from all over the world. This means we come to specific challenges in our work from slightly different perspectives. We strive to promote the creativity and ideas of all members of the team. I think being able to discuss each other’s research in an open, supportive environment has strengthened the quality of work we are capable of.

It is an honour to receive this award, especially coming from a Spanish society that values and celebrates the talent in our country. This award not only acknowledges our group’s scientific vision and collaborative approach, but also highlights the importance of the research area we have chosen to focus on. Diseases that affect women have historically been underestimated and little explored, despite the impact they have on our society.

Through the award, I am looking forward to the connections and collaborations I can build with other Spanish researchers and institutions. The Spanish Researcher in the UK (SRUK/CERU) membership spans across many disciplines, meaning I can disseminate our group’s research to not just our community of researchers in genomics and immunology but more broadly to get across the importance of researching women’s health.

The award also comes with a pot of funding – we are using this to call for more research into endometriosis and other women’s health issues.

Women have historically been underrepresented in the research community, but this is changing. I have been very grateful for people I admire showing me what good leadership is and championing fairer, representative teams, for example Dr Sarah Teichmann.

Progress in the ways we do our science and support our diverse, female scientists will ultimately lead to richer perspectives and more innovative solutions in scientific research. More and more people and journals are starting to catch up.

Oxana Nashchekina, Technical Specialist, working in Cellular Genetics laboratories

In my research group specifically, we want to build on our work combining genomics and organoids. Advances in single-cell transcriptomics continue to teach us more about the microenvironment in order to make our in vitro organoids more realistic for higher-scale perturbations and could allow us to define drug targets in the future. Across the field, new technologies open up a big opportunity to transform women’s health. I hope my team and I are contributing to this.

We congratulate Roser on being awarded the Emerging Talent Award from the Society of Spanish Researchers in the UK (SRUK/CERU), which recognises her outstanding contributions to the field of genomics and bioinformatics toward a better understanding of transcriptional regulatory circuits. By developing and applying new molecular and computational techniques, Roser’s research sheds light into mucosal tissues and immunity, with a strong interest in reproductive tissues.

Read the SRUK/CERU press release announcing Roser’s award here.

1. https://www.who.int/news-room/fact-sheets/detail/endometriosis
2. R. Hadfield et al., Human Reproduction (1996) https://doi.org/10.1093/oxfordjournals.humrep.a019270
3. K. Smith, Nature (2023) https://www.nature.com/immersive/d41586-023-01475-2/index.html

Dr Roser Vento-Tormo's profile at the Sanger Institute

Vento-Tormo research group at the Sanger Institute

VenTo Lab group

The Human Cell Atlas consortium website

CellPhoneDB software

Sanger Seminar Series