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Lateral plate mesoderm directs human amnion and ventral skin organoid formation

ABSTRACT: Recently, we demonstrated that craniofacial skin, including dermis, epidermis, and hair, can be derived by manipulating signaling factors to co-induce epidermal-dermal progenitors. Here, we advance this approach by controlling the size and composition of cranial skin organoids (cSkOs) and incorporating lateral plate mesoderm (LPM) cells to create ventral skin organoids (vSkOs) and human amnion-like structures, termed Amnioids. Amnioids, resembling their extra-embryonic counterparts, are avascular and rapidly expand into large, hairless cysts, while vSkOs develop primitive vasculature and numerous hair follicles. Single-cell RNA sequencing identified distinct gene expression patterns and developmental trajectories, revealing the critical roles of Wnt and YAP/Hippo signaling in directing divergent fates. Functional experiments underscored the importance of mechanical forces and mesenchymal-epithelial interactions in shaping tissue growth and organization. This study presents a novel in vitro model to explore the interface of embryonic and extraembryonic tissues, with implications for understanding congenital disorders and advancing regenerative medicine.

ORGANISM(S): Homo sapiens

PROVIDER: GSE303380 | GEO | 2026/07/22

REPOSITORIES: GEO

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Project description:Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly specify somatic cell fates in cells such as pancreatic ? cells, contractile cardiomyocytes and neurons. We hypothesized that combinatorial expression of chondrocyte-specific transcription factors could directly convert human amnion cells into chondrosarcoma. Starting from a pool of candidate genes, we identified a combination of only five genes (5F pool), BCL6, T (also called BRACHYURY), c-MYC, MITF and BAF60C (also called SMARCD3) that rapidly and efficiently convert postnatal human amnion into chondrosarcoma. The cells generated expressed multiple cartilage-specific genes such as collagen type II ?1, link protein-1 and aggrecan, and exhibited characteristics of cartilage both in vivo and in vitro. Expression of the endogenous genes for T and MITF was initiated, implying that the cell conversion is due to not only the forced expression of the transgenes, but also the cellular reprogramming by the transgenes. The same set of genes converted human placental artery-derived endothelial (hPAE) cells and menstrual blood-derived cells into chondrosarcoma cells, implying that this conversion is independent of cell types. Direct conversion system from non-cartilage tissue to cartilaginous tissue contributes substantially to a major advance toward cartilage development, oncogenesis of chondrocytes, and cell-based therapy. We hypothesized that combinatorial expression of chondrocyte-specific transcription factors could directly convert human amnion cells into chondrosarcoma. Starting from a pool of candidate genes, we identified a combination of only five genes that rapidly efficiently convert postnatal human amnion into chondrosarcoma.

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Lateral plate mesoderm directs human amnion and ventral skin organoid formation

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