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

Sahu, S and Sahoo, S and Sullivan, T and O'Sullivan, TN and Turan, S and Albaugh, ME and Burkett, S and Tran, B and Salomon, DS and Kozlov, SV and Koehler, KR and Jolly, MK and Sharan, SK (2024) Spatiotemporal modulation of growth factors directs the generation of multilineage mouse embryonic stem cell-derived mammary organoids. In: Developmental Cell, 59 (2). 175-186.e8.

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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. © 2023

Item Type:	Journal Article
Publication:	Developmental Cell
Publisher:	Cell Press
Additional Information:	The copyright for this article belongs to Cell Press.
Department/Centre:	Others
Date Deposited:	01 Mar 2024 07:25
Last Modified:	01 Mar 2024 07:25
URI:	https://eprints.iisc.ac.in/id/eprint/83928

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