Dataset Information

Using patient-derived organoids to predict locally advanced or metastatic lung cancer tumor response: a real-world study

ABSTRACT: Using patient derived lung cancer organoids to predict clinical response and find theraputic mechanisms

ORGANISM(S): Homo Sapiens

SUBMITTER: Zexin Chen

PROVIDER: PXD037076 | iProX | Mon Sep 26 00:00:00 BST 2022

REPOSITORIES: iProX

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Using patient-derived organoids to predict locally advanced or metastatic lung cancer tumor response: A real-world study.

Wang Han-Min HM Zhang Chan-Yuan CY Peng Kai-Cheng KC Chen Ze-Xin ZX Su Jun-Wei JW Li Yu-Fa YF Li Wen-Feng WF Gao Qing-Yun QY Zhang Shi-Ling SL Chen Yu-Qing YQ Zhou Qing Q Xu Cong C Xu Chong-Rui CR Wang Zhen Z Su Jian J Yan Hong-Hong HH Zhang Xu-Chao XC Chen Hua-Jun HJ Wu Yi-Long YL Yang Jin-Ji JJ

Cell reports. Medicine 20230118 2

Predicting the clinical response to chemotherapeutic or targeted treatment in patients with locally advanced or metastatic lung cancer requires an accurate and affordable tool. Tumor organoids are a potential approach in precision medicine for predicting the clinical response to treatment. However, their clinical application in lung cancer has rarely been reported because of the difficulty in generating pure tumor organoids. In this study, we have generated 214 cancer organoids from 107 patients ...[more]

PMID: 36657446

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Project description:Underdeveloped lungs are the primary cause of death in premature infants, however, little is known about stem and progenitor cell maintenance during human lung development. In this study, we have identified that FGF7, Retinoic Acid and CHIR-99021, a small molecule that inhibits GSK3 to activate Wnt signaling, support in vitro maintenance of primary human fetal lung bud tip progenitor cells in a progenitor state. Furthermore, these factors are sufficient to derive a population of human bud tip-like progenitor cells in 3D organoid structures from human pluripotent stem cells (hPSC). Functional studies showed that hPSC-derived bud tip progenitor organoids do not contain any mesenchymal cell types, maintain multilineage potential in vitro and are able to engraft into the airways of injured mice and respond to systemic factors. We performed RNA-sequencing to assess the degree of similarity in global gene expression profiles between the full human fetal lung (59-127 days gestation), isolated human fetal bud tip progenitors, organoids grown from primary fetal bud tip progenitors, and hPSC-derived bud tip organoids. Results showed that hPSC-derived organoids have molecular profiles similar to organoids generated from primary human fetal lung tissue. Gene expression differences between hPSC-derived bud tip organoids and fetal progenitor organoids may be related to the presence of contaminating mesenchymal cells in primary cultures. hPSC-derived bud tip organoids are generated from a well-defined human cell sources, offering a distinct advantage over rare primary tissue as a means to study human specific lung development, homeostasis and disease. Sample Nomenclature - Description ------------------------------------------------------------------------- Peripheral fetal lung the distal/peripheral portion of the fetal lung (i.e., distal 0.5 cm) was excised from the rest of the lung using a scalpel. This includes all components of the lung (e.g., epithelial, mesenchymal, vascular). Isolated fetal bud tip the bud peripheral portion of the fetal lung was excised with a scalpel and subjected to enzymatic digestion and microdissection. The epithelium was dissected and separated from the mesenchyme, but a small amount of associated mesenchyme likely remained. Fetal progenitor organoid 3D organoid structures that arose from culturing isolated fetal epithelial bud tips. Foregut spheroid 3D foregut endoderm structure as described in Dye et al. (2015). Gives rise to patterned lung organoid (PLO) when grown in 3F medium. Patterned lung organoid (PLO) lung organoids that were generated by differentiating hPSCs, as described throughout the manuscript. Bud tip organoid organoids derived from PLOs, enriched for SOX2/SOX9 co-expressing cells, and grown/passaged in 3F medium.

Dataset Information

Using patient-derived organoids to predict locally advanced or metastatic lung cancer tumor response: a real-world study

Publications

Using patient-derived organoids to predict locally advanced or metastatic lung cancer tumor response: A real-world study.

Similar Datasets

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