دورية أكاديمية
أعرض في EDS

Cellular and transcriptional diversity over the course of human lactation.

التفاصيل البيبلوغرافية
العنوان: Cellular and transcriptional diversity over the course of human lactation.
المؤلفون: Nyquist SK; Broad Institute of MIT and Harvard, Cambridge, MA 02142.; Program in Computational and Systems Biology, Massachusetts Institute of Technology; Cambridge, MA 02139.; Department of Chemistry and Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139.; Computer Science and Artificial Intelligence Laboratory, Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA 02139., Gao P; Department of Chemistry and Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139., Haining TKJ; Department of Chemistry and Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139., Retchin MR; Department of Chemistry and Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139., Golan Y; Department of Bioengineering and Therapeutic Sciences, Institute for Human Genetics, University of California, San Francisco, CA 94143., Drake RS; Broad Institute of MIT and Harvard, Cambridge, MA 02142.; Department of Chemistry and Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139.; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139., Kolb K; Broad Institute of MIT and Harvard, Cambridge, MA 02142.; Department of Chemistry and Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139., Mead BE; Broad Institute of MIT and Harvard, Cambridge, MA 02142.; Department of Chemistry and Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139., Ahituv N; Department of Bioengineering and Therapeutic Sciences, Institute for Human Genetics, University of California, San Francisco, CA 94143., Martinez ME; Department of Biology, Emory University, Atlanta, GA 30322., Shalek AK; Broad Institute of MIT and Harvard, Cambridge, MA 02142.; Program in Computational and Systems Biology, Massachusetts Institute of Technology; Cambridge, MA 02139.; Department of Chemistry and Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139.; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.; Division of Health Science & Technology, Harvard Medical School, Boston, MA 02115.; Department of Immunology, Massachusetts General Hospital, Boston, MA 02114., Berger B; Broad Institute of MIT and Harvard, Cambridge, MA 02142.; Computer Science and Artificial Intelligence Laboratory, Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA 02139., Goods BA; Thayer School of Engineering, Program in Quantitative Biomedical Sciences, Dartmouth College, Hanover, NH 03755.
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Apr 12; Vol. 119 (15), pp. e2121720119. Date of Electronic Publication: 2022 Apr 04.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH: Lactation*/genetics , Milk, Human*/cytology , Milk, Human*/metabolism, Breast Feeding ; Female ; Gene Expression Profiling ; Humans ; RNA-Seq ; Transcriptome
مستخلص: Human breast milk (hBM) is a dynamic fluid that contains millions of cells, but their identities and phenotypic properties are poorly understood. We generated and analyzed single-cell RNA-sequencing (scRNA-seq) data to characterize the transcriptomes of cells from hBM across lactational time from 3 to 632 d postpartum in 15 donors. We found that the majority of cells in hBM are lactocytes, a specialized epithelial subset, and that cell-type frequencies shift over the course of lactation, yielding greater epithelial diversity at later points. Analysis of lactocytes reveals a continuum of cell states characterized by transcriptional changes in hormone-, growth factor-, and milk production-related pathways. Generalized additive models suggest that one subcluster, LC1 epithelial cells, increases as a function of time postpartum, daycare attendance, and the use of hormonal birth control. We identify several subclusters of macrophages in hBM that are enriched for tolerogenic functions, possibly playing a role in protecting the mammary gland during lactation. Our description of the cellular components of breast milk, their association with maternal–infant dyad metadata, and our quantification of alterations at the gene and pathway levels provide a detailed longitudinal picture of hBM cells across lactational time. This work paves the way for future investigations of how a potential division of cellular labor and differential hormone regulation might be leveraged therapeutically to support healthy lactation and potentially aid in milk production.
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معلومات مُعتمدة: P30 DK063720 United States DK NIDDK NIH HHS; P30-CA14051 United States GF NIH HHS; P30 CA014051 United States CA NCI NIH HHS; F32-AI136459 United States GF NIH HHS; R01 HG010959 United States HG NHGRI NIH HHS; T32 GM087237 United States GM NIGMS NIH HHS; DP5 OD023100 United States OD NIH HHS; F32 AI136459 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: breast milk; macrophage; mammary epithelial cell; maternal health; single-cell RNA-sequencing
تواريخ الأحداث: Date Created: 20220404 Date Completed: 20220415 Latest Revision: 20240214
رمز التحديث: 20240214
مُعرف محوري في PubMed: PMC9169737
DOI: 10.1073/pnas.2121720119
PMID: 35377806
قاعدة البيانات: MEDLINE
الوصف
تدمد:1091-6490
DOI:10.1073/pnas.2121720119