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Spatiotemporal modulation of growth factors directs the generation of multilineage mouse embryonic stem cell-derived mammary organoids

  1. Author:
    Sahu,Sounak
    Sahoo, Sarthak
    Sullivan,Teresa
    O'Sullivan,Theresa
    Turan,Sevilay
    Albaugh,Mary
    Burkett,Sandra
    Tran,Bao
    Salomon,David
    Kozlov,Serguei
    Koehler, Karl R
    Jolly, Mohit Kumar
    Sharan,Shyam

  2. Author Address

    Mouse Cancer Genetics Program (MCGP), Centre for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA., Department of Bioengineering, Indian Institute of Science, Bengaluru 560012, India., Centre for Advanced Preclinical Research (CAPR), National Cancer Institute, Frederick, MD 21702, USA., Leidos Biomedical Sciences, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Mouse Cancer Genetics Program (MCGP), Centre for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; Leidos Biomedical Sciences, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Centre for Advanced Preclinical Research (CAPR), National Cancer Institute, Frederick, MD 21702, USA; Leidos Biomedical Sciences, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA 02115, USA; Department of Otolaryngology, Department of Plastic & Oral Surgery, and the F.M. Kirby Neurobiology Center, Boston Children 39;s Hospital, Boston, MA 02115, USA., Mouse Cancer Genetics Program (MCGP), Centre for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; Centre for Advanced Preclinical Research (CAPR), National Cancer Institute, Frederick, MD 21702, USA. Electronic address: sharans@mail.nih.gov.,
    1. Year: 2024
    2. Date: Jan 22
    3. Epub Date: 2023 12 26
  2. Journal: Developmental Cell
    1. 59
  4. Type of Article: Article
  1. Abstract:

    Ectodermal appendages, such as the mammary gland (MG), are thought to have evolved from hair-associated apocrine glands to serve the function of milk secretion. Through the directed differentiation of mouse embryonic stem cells (mESCs), here, we report the generation of multilineage ESC-derived mammary organoids (MEMOs). We adapted the skin organoid model, inducing the dermal mesenchyme to transform into mammary-specific mesenchyme via the sequential activation of Bone Morphogenetic Protein 4 (BMP4) and Parathyroid Hormone-related Protein (PTHrP) and inhibition of hedgehog (HH) signaling. Using single-cell RNA sequencing, we identified gene expression profiles that demonstrate the presence of mammary-specific epithelial cells, fibroblasts, and adipocytes. MEMOs undergo ductal morphogenesis in Matrigel and can reconstitute the MG in vivo. Further, we demonstrate that the loss of function in placode regulators LEF1 and TBX3 in mESCs results in impaired skin and MEMO generation. In summary, our MEMO model is a robust tool for studying the development of ectodermal appendages, and it provides a foundation for regenerative medicine and disease modeling. Published by Elsevier Inc.

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External Sources

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  2. DOI: 10.1016/j.devcel.2023.12.003
  3. PMID: 38159568
  4. PII : S1534-5807(23)00653-6

Library Notes

  1. Fiscal Year: FY2023-2024
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