A5025127000- Infant Nutrition and Health
- Cancer Cells and Metastasis
- Neonatal Respiratory Health Research
- Breastfeeding Practices and Influences
- Pluripotent Stem Cells Research
- Digestive system and related health
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Animal Genetics and Reproduction
- Breast Cancer Treatment Studies
- Tissue Engineering and Regenerative Medicine
- Biomedical Ethics and Regulation
- Mesenchymal stem cell research
- Probiotics and Fermented Foods
- Cancer-related molecular mechanisms research
- Cell Image Analysis Techniques
- Child Nutrition and Feeding Issues
- Pediatric health and respiratory diseases
- Protein Hydrolysis and Bioactive Peptides
- Estrogen and related hormone effects
- CRISPR and Genetic Engineering
- Cancer Risks and Factors
- Advanced Breast Cancer Therapies
- RNA modifications and cancer
University of Cambridge
2020-2025
Wellcome/MRC Cambridge Stem Cell Institute
2021-2023
Stem Cell Institute
2023
Helmholtz Zentrum München
2017-2022
The University of Western Australia
2012-2017
Abstract The mammary gland undergoes significant remodeling during pregnancy and lactation, which is fuelled by controlled stem cell (MaSC) proliferation. scarcity of human lactating breast tissue specimens the low numbers quiescent state MaSCs in resting have hindered understanding both normal MaSC dynamics molecular determinants that drive their aberrant self-renewal cancer. Here, we demonstrate breastmilk contains cells (hBSCs) with multilineage properties. Breastmilk from different...
Abstract Here we use single-cell RNA sequencing to compile a human breast cell atlas assembled from 55 donors that had undergone reduction mammoplasties or risk mastectomies. From more than 800,000 cells identified 41 subclusters across the epithelial, immune and stromal compartments. The contribution of these different clusters varied according natural history tissue. Age, parity germline mutations, known modulate developing cancer, affected homeostatic cellular state in ways. We found...
Abstract Under normal conditions, the most significant expansion and differentiation of adult mammary gland occurs in response to systemic reproductive hormones during pregnancy lactation enable milk synthesis secretion sustain offspring. However, human tissue remodelling that takes place remains poorly understood due challenge acquiring samples. We report here single-cell transcriptomic analysis 110,744 viable breast cells isolated from or non-lactating tissue, nine seven donors,...
Abstract Breastmilk is a rich source of cells with heterogeneous composition comprising early-stage stem cells, progenitors and more differentiated cells. The gene expression profiles these their associations characteristics the breastfeeding mother infant are poorly understood. This study investigated factors associated cellular dynamics breastmilk explored variations amongst women. Genes representing different cell populations including mammary epithelial myoepithelial multi-lineage showed...
Large inter- and intra-individual variations exist in breastmilk composition, yet factors associated with these the short-term are not well understood. In this study, effects of breastfeeding on cellular biochemical content were examined. Serial samples (∼5 mL) collected from both breasts women before immediately after first morning breastfeed, then at 30-minute intervals for up to 3 hours post-feed 2–4 mornings per participant. The infant fed one breast only each feed. Effects pump versus...
Mam-mary stem cells are responsible for the changes that occur in breast during this period, which can be repeated many times life of a female. What is less well known these cells, together with other cell types from breast, filter down into milk and ingested by breastfeeding child. Interestingly, human have been recently shown to pluripotent features. This means they able differentiate not only breast-specific but also types, including neural-like cells.
Abstract One of the barriers for breast cancer prevention and treatment is our poor understanding dynamic cellular shifts that naturally occur within how these changes contribute to tumour initiation. In this study we report use single cell RNA sequencing (scRNAseq) compile a Human Breast Cell Atlas (HBCA) assembled from 55 donors had undergone reduction mammoplasties or risk mammoplasties. The data more than 800,000 cells identified 41 subclusters distributed across epithelial, immune,...
Human milk oligosaccharides (HMOs) are integral to infant health. Yet, their complex biosynthesis pathways in the mammary gland during lactation remain under characterized. To address this knowledge gap, we performed integrated analyses of single-cell RNA-sequencing (scRNA-seq) datasets combined with select HMO concentration measures. We identify differential expression patterns known synthesis genes epithelial subsets and nominate several candidate that vary concentration. Additionally,...
Human milk has been previously found to contain various types of leukocytes however specific characteristics these cells, such as whether they cytolytic antimicrobial proteins that may induce pathogen directed cell death, are unknown. This project aims examine the presence and localization immune perforin, granulysin granzymes in human cells at protein mRNA level. Genes encoding were confirmed samples, which particularly enriched early case maternal infection. Fluorescence activated sorting...
Abstract Over the past decade, cellular content of human milk has been a focus in lactation research due to benefit potential non-invasive stem cell compartment could provide either infant or for therapeutic applications. Despite an increase number studies this field, fundamental knowledge regard identification and characterisation is still lacking. In project, we investigated nature, morphology membrane enclosed structures (MESs) explored different methods enrich cells (HMCs) whilst...
Abstract Findings from epidemiological studies suggest that breast cancer risk is influenced by parity in an age-dependent manner. However, human mammary tissue remodelling takes place during pregnancy and lactation remain little understood due to the challenge of acquiring samples. Here, we present approach overcome this using single-cell RNA sequencing examine viable primary epithelial cells isolated milk compared resting, non-lactating tissue. Thereby, determined separate tissue, largely...
Summary Single-cell transcriptomics provide insights into cellular heterogeneity and lineage dynamics that are key to better understanding normal mammary gland function as well breast cancer initiation progression. In contrast murine tissue, human glands require laborious dissociation protocols isolate single cells. This leads unavoidable procedure-induced compositional transcriptional bias. Here, we present a new strategy on how identify minimize systematic error by combining different...
An international cohort of over 300 stem cell biologists came together in Heidelberg, Germany May 2017 as delegates the 'Advances Stem Cells and Regenerative Medicine' conference run through European Molecular Biology Organization. This Meeting Review highlights novel insights into regulation, new technologies aiding discovery exciting breakthroughs field regenerative medicine that emerged from meeting.
Abstract Background The luminal progenitor (LP) population in the normal breast is under control of paracrine progesterone signalling and likely represents cell origin estrogen receptor negative (ER-) BC. Exogenous progestins, as contraception or menopausal hormone replacement therapy (HRT), increase risk ER- ER+ We sought to examine effect antagonism on tissue composition cellular hierarchy human thus potential for cancer prevention. Methods BC-APPS1 a single arm phase 2 pilot study which...
Abstract The thirteenth annual workshop of the European Network for Breast Development and Cancer (ENBDC) Laboratories Annual Workshop took place on 28–30 April 2022 in Weggis, Switzerland focused methods mammary gland biology breast cancer. Sixty scientists participated ENBDC which had not been held person since 2019 due to global COVID-19 pandemic. Topics spanned field, ranging from lactation embryonic development, single cell sequencing human breast, stunning cutting-edge imaging mouse as...
Neurotrophins are growth factors primarily described in the development of nervous system. They secreted by developing organs to attract nerve fibres, acting as molecular mediators for establishment connections with Recent evidence demonstrates that mammary cells synthesize neurotrophins; however, variation their expression is poorly understood. In this study, we examined a panel key neurotrophins and receptors normal breast. Rare specimens human resting lactating breast tissue were stained...
Breastmilk contains a cellular hierarchy including pluripotent stem cells, progenitor and differentiated epithelial cells leukocytes. The latter are strongly associated with the health status of mother/infant dyad. Little is known about variation in content non‐leukocytic breastmilk cells. In this study, we used RT‐PCR to examine expression genes representative different cell types from over 50 healthy dyads Australia USA, effects lactation stage. Pluripotency were expressed at varying...
Introduction Perceived or actual low milk supply is the leading cause of early breastfeeding cessation worldwide. Monitoring 24 hour production profiles can help diagnose which may be improved with pumping regimes and support. Despite this, some cases persist. Human cells are increasingly being utilised to provide non‐invasive access mammary epithelial allowing investigations into lactocyte characteristics metabolism. Problem Statement The molecular mechanisms behind impaired lactation in...
Background Early human milk (HM) contains a large variety of immune components, including leucocytes, providing protection to the newborn infant. Peptides such as perforin, granulysin and granzymes, stored in lymphocytes work together induce apoptosis infected host cells pathogens bacteria parasites. Thus far their presence HM has not been shown. Aims This project aims examine localization these peptides cells. Methods Presence granzymes (A, B, H M) was examined isolated from samples...