دورية أكاديمية
Cellular and transcriptional diversity over the course of human lactation.
العنوان: | Cellular and transcriptional diversity over the course of human lactation. |
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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. |
References: | Am J Physiol Endocrinol Metab. 2013 Sep 15;305(6):E700-16. (PMID: 23880316) Sci Rep. 2017 Jan 03;7:39921. (PMID: 28045081) Clin Transl Immunology. 2013 Apr 12;2(4):e3. (PMID: 25505951) Pediatr Res. 2019 Jun;85(7):936-942. (PMID: 30858473) Stem Cells. 2012 Oct;30(10):2164-74. (PMID: 22865647) Lancet. 2016 Jan 30;387(10017):475-90. (PMID: 26869575) Cancer Causes Control. 2007 Jun;18(5):517-23. (PMID: 17450440) J Natl Cancer Inst. 2000 Feb 16;92(4):302-12. (PMID: 10675379) Cell. 2021 Mar 18;184(6):1486-1499. (PMID: 33740451) J Mammary Gland Biol Neoplasia. 2020 Dec;25(4):367-387. (PMID: 33216249) Mol Cell Biol. 2004 Sep;24(18):8037-47. (PMID: 15340066) Nature. 2018 Aug;560(7720):649-654. (PMID: 30135581) Dev Biol. 2001 Jan 1;229(1):163-75. (PMID: 11133161) Am J Pathol. 2010 Mar;176(3):1241-55. (PMID: 20110414) Trends Immunol. 2020 Mar;41(3):225-239. (PMID: 32057705) Matern Child Nutr. 2017 Jan;13(1):. (PMID: 26776058) Sci Rep. 2020 Aug 31;10(1):14333. (PMID: 32868786) EMBO J. 1994 Sep 15;13(18):4361-9. (PMID: 7925280) J Mammary Gland Biol Neoplasia. 2012 Jun;17(2):167-88. (PMID: 22752723) Genes Dev. 1997 Jan 15;11(2):179-86. (PMID: 9009201) Front Immunol. 2015 Aug 19;6:415. (PMID: 26347740) Mediators Inflamm. 2005 Dec 14;2005(6):331-6. (PMID: 16489252) PLoS One. 2015 Aug 19;10(8):e0135580. (PMID: 26288195) J Mammary Gland Biol Neoplasia. 2021 Mar;26(1):3-8. (PMID: 34097179) Pediatr Res. 2012 Feb;71(2):220-5. (PMID: 22258136) Pediatr Res. 1999 Aug;46(2):194-9. (PMID: 10447115) Am J Clin Nutr. 2021 May 8;113(5):1063-1072. (PMID: 33831952) Genome Biol. 2014;15(12):550. (PMID: 25516281) Int Breastfeed J. 2020 May 25;15(1):49. (PMID: 32450886) J Exp Med. 2017 May 1;214(5):1281-1296. (PMID: 28432199) Biochim Biophys Acta. 2016 Aug;1863(8):2006-16. (PMID: 27130254) J Mammary Gland Biol Neoplasia. 2002 Jan;7(1):49-66. (PMID: 12160086) Front Cell Dev Biol. 2020 Nov 17;8:604896. (PMID: 33282878) Immunity. 2020 Oct 13;53(4):878-894.e7. (PMID: 33053333) Genome Biol. 2018 Feb 6;19(1):15. (PMID: 29409532) Nat Commun. 2022 Jan 28;13(1):562. (PMID: 35091553) Eur J Immunol. 2019 Jul;49(7):1001-1014. (PMID: 30900752) Nat Genet. 2000 May;25(1):25-9. (PMID: 10802651) Physiol Genomics. 2010 Mar 3;41(1):21-32. (PMID: 19996161) Breastfeed Med. 2014 Dec;9(10):530-7. (PMID: 25380323) Best Pract Res Clin Endocrinol Metab. 2017 Aug;31(4):409-418. (PMID: 29221569) BMC Immunol. 2018 Oct 30;19(1):30. (PMID: 30376808) Nutrients. 2018 Aug 20;10(8):. (PMID: 30127252) Mol Cell Endocrinol. 2002 Nov 29;197(1-2):127-31. (PMID: 12431805) Nat Med. 2020 Apr;26(4):511-518. (PMID: 32251406) Lancet. 2003 Jul 5;362(9377):65-71. (PMID: 12853204) Front Nutr. 2020 Jul 29;7:110. (PMID: 32850934) Nat Rev Mol Cell Biol. 2011 Feb;12(2):104-17. (PMID: 21252999) Nat Methods. 2020 Feb;17(2):137-145. (PMID: 31792435) Am J Clin Nutr. 1991 Jul;54(1):69-80. (PMID: 2058590) J Immunol. 2006 Nov 15;177(10):7303-11. (PMID: 17082649) Proc Natl Acad Sci U S A. 2022 Apr 12;119(15):e2121720119. (PMID: 35377806) Anim Genet. 2010 Feb;41(1):55-63. (PMID: 19793270) Science. 2018 Jun 29;360(6396):1401-1402. (PMID: 29954968) Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):2946-51. (PMID: 23382184) J Mammary Gland Biol Neoplasia. 2003 Jul;8(3):287-307. (PMID: 14973374) Cell Syst. 2019 Apr 24;8(4):281-291.e9. (PMID: 30954476) PLoS One. 2016 Jun 10;11(6):e0156762. (PMID: 27285085) Cell Mol Biol Lett. 2017 Jul 13;22:11. (PMID: 28717367) Nat Commun. 2018 May 23;9(1):2028. (PMID: 29795293) Mol Endocrinol. 2004 Jul;18(7):1670-86. (PMID: 15071091) Cell. 2019 Jun 13;177(7):1888-1902.e21. (PMID: 31178118) Pediatr Allergy Immunol. 2018 Mar;29(2):133-143. (PMID: 29197124) Nat Cell Biol. 2020 May;22(5):546-558. (PMID: 32341550) Anal Chem. 2019 Nov 5;91(21):13314-13323. (PMID: 31549807) Cell. 2016 May 5;165(4):827-41. (PMID: 27153495) Funct Integr Genomics. 2016 May;16(3):297-321. (PMID: 26909879) Nat Commun. 2020 Nov 30;11(1):6077. (PMID: 33257685) Immunity. 2021 Aug 10;54(8):1883-1900.e5. (PMID: 34331874) Nat Commun. 2018 Nov 27;9(1):5010. (PMID: 30479342) Mol Cell Endocrinol. 2021 Jan 15;520:111081. (PMID: 33181234) J Hum Lact. 2012 Nov;28(4):522-8. (PMID: 22729710) EMBO J. 1988 Jul;7(7):2089-95. (PMID: 3416834) Nat Methods. 2017 Apr;14(4):395-398. (PMID: 28192419) J Nutr. 2021 Apr 8;151(4):826-839. (PMID: 33693758) Genome Biol. 2019 Oct 17;20(1):210. (PMID: 31623682) PLoS One. 2013 Jul 05;8(7):e67531. (PMID: 23861770) J Extracell Vesicles. 2014 Aug 14;3:. (PMID: 25206958) Am J Physiol Gastrointest Liver Physiol. 2010 May;298(5):G582-9. (PMID: 20203060) Cell Metab. 2006 Dec;4(6):475-90. (PMID: 17141631) Adv Exp Med Biol. 2001;501:241-7. (PMID: 11787687) Nutrients. 2019 Jul 04;11(7):. (PMID: 31277502) Sci Rep. 2015 Aug 10;5:12933. (PMID: 26255679) |
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 |
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