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Prrx1 labels stromal stem cells that contribute to the homeostasis and damage repair of the connective tissues

ABSTRACT: Prrx1 labels stromal stem cells that contribute to the homeostasis and damage repair of the connective tissues

PROVIDER: PRJNA474495 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7255320_1.fastq.gz	Fastqsanger.gz
	SRR7255320_2.fastq.gz	Fastqsanger.gz
	SRR7255330_1.fastq.gz	Fastqsanger.gz
	SRR7255330_2.fastq.gz	Fastqsanger.gz
	SRR7255340_1.fastq.gz	Fastqsanger.gz

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Prrx1 labels stromal stem cells that contribute to the homeostasis and damage repair of the connective tissues

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Project description:To investigate downstream targets of PRRX1, we used MDA-MB-231 (MDA231) breast cancer cells which express low level of PRRX1 to generate a stable cell line where human PRRX1 was ectopically overexpressed (MDA231-PRRX1), and performed comparative microarray analyses. Interestingly, we found many miRNAs that were upregulated in MDA231-PRRX1 cells.

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Prrx1 is a Master Transcription Factor of myofibroblastic Cancer-Associated Fibroblasts [Murine_Fibroblast_ChIP_seq]

Project description:Although cancer associated fibroblasts (CAF) play a critical role in cancer progression, their identities are still unknown. Because cells’ own identity is determined by core regulatory circuit (CRC) comprising master transcription factors (TFs), it is critical to find CAF’s master TF. Therefore, we attempt to find master TF of CAF through the extensive screening of single cell RNA-seq database of cancer tissues, and discovered Prrx1, master regulator of embryonic mesenchymal cells, as candidate for master TF of CAF. Prrx1 was abundantly expressed in CAFs with significant correlation with unfavorable clinical outcomes. Furthermore, Prrx1 in fibroblasts dramatically enhanced tumor progression and metastasis in fibroblast-specific Prrx1 inducible mice. On the other hand, tumor formation was severely inhibited in conditional Prrx1 knock-down mice. Finally, we confirmed that Prrx1 is a master TF of CAF and normal fibroblast executing wound healing program using ChIP-SEQ, CRC modeling, and in vivo validation. Furthermore we also revealed that targeting Prrx1 in fibroblast alone induced complete remission of chemotherapy-resistant cancer in preclinical mouse experiments.

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Prrx1 is a Master Transcription Factor of myofibroblastic Cancer-Associated Fibroblasts [Murine_Wound_Tissue_scRNAseq]

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Prrx1 is a Master Transcription Factor of myofibroblastic Cancer-Associated Fibroblasts [Murine_Fibroblast_RNA_seq]

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