Single Cell RNA Sequencing of Human Milk-Derived Cells Reveals Sub-Populations of Mammary Epithelial Cells with Molecular Signatures of Progenitor and Mature States: a Novel, Non-invasive Framework for Investigating Human Lactation Physiology

Carli, Jayne F. Martin; Trahan, G. Devon; Jones, Kenneth L.; Hirsch, Nicole; Rolloff, Kristy; Dunn, Emily; Friedman, Jacob E.; Barbour, Linda A.; Hernandez, Teri L.; MacLean, Paul S.; Monks, Jenifer; McManaman, James L.; Rudolph, Michael C.

doi:10.1007/s10911-020-09466-z

Cited by 33 publications

(36 citation statements)

References 90 publications

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“…As another demonstration of this heterogeneity, a comparison of total RNA from milk fat to that from biopsied mammary tissue or shed epithelial cells revealed that the abundance of LALBA transcripts was greater in the former [71]. In a similar way, Carli et al recently identified that among MEC shed into human milk there were many functionally-distinct cells (> 35%) that they proposed might sub-specialize in lactose production, while others (4%) were suggested as being primarily responsible for the synthesis of milk proteins and lipids [72]. We suggest it is more likely that this differential expression of lactose, protein and lipid synthesis across MEC reflects the heterogeneity and acute temporal regulation of milk synthesis in the gland at any given time.…”

Section: Variation In Lalba Distributionmentioning

confidence: 88%

A Comparative Review of the Cell Biology, Biochemistry, and Genetics of Lactose Synthesis

Sadovnikova

García

Hovey

2021

J Mammary Gland Biol Neoplasia

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Lactose is the primary carbohydrate in the milk of most mammals and is unique in that it is only synthesized by epithelial cells in the mammary glands. Lactose is also essential for the development and nutrition of infants. Across species, the concentration of lactose in milk holds a strong positive correlation with overall milk volume. Additionally, there is a range of examples where the onset of lactose synthesis as well as the content of lactose in milk varies between species and throughout a lactation. Despite this diversity, the precursors, genes, proteins and ions that regulate lactose synthesis have not received the depth of study they likely deserve relative to the significance of this simple and abundant molecule. Through this review, our objective is to highlight the requirements for lactose synthesis at the biochemical, cellular and temporal levels through a comparative approach. This overview also serves as the prelude to a companion review describing the dietary, hormonal, molecular, and genetic factors that regulate lactose synthesis.

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Section: Variation In Lalba Distributionmentioning

confidence: 88%

A Comparative Review of the Cell Biology, Biochemistry, and Genetics of Lactose Synthesis

Sadovnikova

García

Hovey

2021

J Mammary Gland Biol Neoplasia

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“…The luminal cells however were found to have a continuum of differentiation stemming from Aldh1a3 + luminal progenitors and extend to the two major lineages of secretory alveolar and hormone responsive. Clearly replicating such experiments in humans would prove difficult, hence studies conducting scRNA-seq of human milk cells have provided novel findings on the maturation of functional human mammary cells during lactation [76] , [77] . Recent work from our lab examining milk cells from 4 donors and 4 non-lactating breast tissue samples found two populations of secretory luminal milk derived cells which are transcriptionally similar to luminal progenitor cells from non-lactating breast [76] .…”

Section: Using Single Cell Technologies To Understand Mammary Gland Biologymentioning

confidence: 99%

Mammary gland development from a single cell ‘omics view

Twigger

Khaled

2021

Seminars in Cell & Developmental Biology

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Understanding the complexity and heterogeneity of mammary cell subpopulations is vital to delineate the mechanisms behind breast cancer development, progression and prevention. Increasingly sophisticated tools for investigating these cell subtypes has led to the development of a greater understanding of these cell subtypes, complex interplay of certain subtypes and their developmental potential. Of note, increasing accessibility and affordability of single cell technologies has led to a plethora of studies being published containing data from mammary cell subtypes and their differentiation potential in both mice and human data sets. Here, we review the different types of single cell technologies and how they have been used to improve our understanding of mammary gland development.

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“…This is problematic because of variable fluorescent antibody quality and unavailability of antibodies for novel cell types in milk. Another limitation is that maternal breastmilk cells are sometimes frozen after collection and before analysis (13). This can be problematic because some populations of breastmilk cells do not survive the freezing process; thus, analysis biases against cell populations that are not sufficiently robust.…”

Section: Introductionmentioning

confidence: 99%

“…Dominant gene expression then shifts in mature stage milk to the two genes responsible for producing milk proteins -α-lactalbumin and β-caseinin mature stage milk (12). Establishing baseline concentrations and gene expression profiles for distinct breastmilk cell types might also aid the development of diagnostics for the detection of cancer in the breastfeeding person (13).…”

Section: Introductionmentioning

confidence: 99%

Profiling of mature stage human breastmilk cells identifies host-defense lactocyte sub-populations

Gleeson

Chaudhary

Doerfler

et al. 2021

Preprint

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Breastmilk is chock-full of nutrients, immunological factors, and cells that aid infant development. Maternal cells are the least studied breastmilk component, and their unique properties are difficult to identify using traditional techniques. Here, we characterized the cells in mature stage breastmilk from healthy donors at the protein, gene, and transcriptome levels. Holistic analysis of flow cytometry, qPCR, and single cell RNA sequencing data identified the predominant cell population as epithelial with smaller populations of macrophages and T cells. Two percent of epithelial cells expressed four stem cell markers: SOX2, TRA-1-60, NANOG, and SSEA4. Furthermore, milk contained six distinct epithelial lactocyte sub-populations, including three previously unidentified sub-populations programmed towards host-defense and intestinal development. Pseudotime analysis delineated the differentiation pathways of epithelial progenitors. Together, these data define healthy human maternal breastmilk cells and provide a basis for their application in maternal and infant medicine.

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Single Cell RNA Sequencing of Human Milk-Derived Cells Reveals Sub-Populations of Mammary Epithelial Cells with Molecular Signatures of Progenitor and Mature States: a Novel, Non-invasive Framework for Investigating Human Lactation Physiology

Cited by 33 publications

References 90 publications

A Comparative Review of the Cell Biology, Biochemistry, and Genetics of Lactose Synthesis

A Comparative Review of the Cell Biology, Biochemistry, and Genetics of Lactose Synthesis

Mammary gland development from a single cell ‘omics view

Profiling of mature stage human breastmilk cells identifies host-defense lactocyte sub-populations

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