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Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21

ABSTRACT: Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21

PROVIDER: PRJNA521070 | ENA |

REPOSITORIES: ENA

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Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21

Project description:Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21

| PRJNA521067 | ENA

Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21

Project description:Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21

| PRJNA521071 | ENA

Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21

Project description:Recent studies indicate that cancer-associated fibroblasts (CAFs) are phenotypically and functionally heterogeneous. However, little is known about CAF subtypes and the roles they play in cancer progression. Here we identify and characterize two CAF subtypes that coexist within high grade serous ovarian cancers: Fibroblast activation protein (FAP)-high (FH) CAFs resemble the classical myofibroblast-type CAF, whereas FAP-low (FL) CAFs possesses a preadipocyte-like molecular signature.

2020-05-01 | GSE126132 | GEO

Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21

Project description:Recent studies indicate that cancer-associated fibroblasts (CAFs) are phenotypically and functionally heterogeneous. However, little is known about CAF subtypes and the roles they play in cancer progression. Here we identify and characterize two CAF subtypes that coexist within high grade serous ovarian cancers: Fibroblast activation protein (FAP)-high (FH) CAFs resemble the classical myofibroblast-type CAF, whereas FAP-low (FL) CAFs possesses a preadipocyte-like molecular signature.

2020-05-01 | GSE126131 | GEO

Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21.

Project description:Recent studies indicate that cancer-associated fibroblasts (CAFs) are phenotypically and functionally heterogeneous. However, little is known about CAF subtypes, the roles they play in cancer progression, and molecular mediators of the CAF "state." Here, we identify a novel cell surface pan-CAF marker, CD49e, and demonstrate that two distinct CAF states, distinguished by expression of fibroblast activation protein (FAP), coexist within the CD49e+ CAF compartment in high-grade serous ovarian cancers. We show for the first time that CAF state influences patient outcomes and that this is mediated by the ability of FAP-high, but not FAP-low, CAFs to aggressively promote proliferation, invasion and therapy resistance of cancer cells. Overexpression of the FAP-low-specific transcription factor TCF21 in FAP-high CAFs decreases their ability to promote invasion, chemoresistance, and in vivo tumor growth, indicating that it acts as a master regulator of the CAF state. Understanding CAF states in more detail could lead to better patient stratification and novel therapeutic strategies.

| S-EPMC7398174 | biostudies-literature

Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-05-01 | GSE126133 | GEO

Autocrine Sfrp1 inhibits fibroblast invasion during transition to injury induced myofibroblasts - Tcf21 labeled mice

Project description:Fibroblast to myofibroblast conversion is a major driver of tissue remodeling in organ fibrosis. Here, we combined spatial transcriptomics, longitudinal single-cell RNA-seq and genetic lineage tracing to study fibroblast fates during mouse lung regeneration. We discovered a transitional fibroblast state characterized by high Sfrp1 expression, derived from both Tcf21-Cre lineage positive and negative cells. Sfrp1+ cells appeared early after injury in peribronchiolar, adventitial and alveolar locations and preceded the emergence of myofibroblasts. We identified lineage specific paracrine signals and inferred converging transcriptional trajectories towards Sfrp1+ transitional fibroblasts and Cthrc1+ myofibroblasts. Tgfβ1 downregulated Sfrp1 in non-invasive transitional cells and induced their switch to an invasive Cthrc1+ myofibroblast identity. Our study reveals the convergence of spatially and transcriptionally distinct fibroblast lineages into transcriptionally uniform myofibroblasts and identifies Sfrp1 as an autocrine inhibitor of fibroblast invasion during early stages of fibrogenesis.

2024-02-15 | GSE207687 | GEO

Tcf21+ mesenchymal cells contribute to testis somatic cell development, homeostasis, and regeneration

Project description:Testicular development and function relies on interactions between somatic cells and the germline, but similar to other organs, regenerative capacity decline in aging and disease. Whether the adult testis maintains a reserve progenitor population with repair or regenerative capacity remains uncertain. Here, we characterized a recently identified mouse testis interstitial population expressing the transcription factor Tcf21. We found that Tcf21+ cells are bipotential somatic progenitors present in fetal testis and ovary, maintain adult testis homeostasis during aging, and act as reserve somatic progenitors following injury. In vitro, Tcf21+ cells are multipotent mesenchymal progenitors which form multiple somatic lineages including Leydig and myoid cells. Additionally, Tcf21+ cells resemble resident fibroblast populations reported in other organs having roles in tissue homeostasis, fibrosis, and regeneration. Our findings reveal that the testis, like other organs, maintains multipotent mesenchymal progenitors that can be leveraged in development of future therapies for hypoandrogenism and/or infertility.

2021-05-08 | GSE151337 | GEO

Autocrine Sfrp1 inhibits fibroblast invasion during transition to injury induced myofibroblasts - Tcf21 labeled mice

Project description:Autocrine Sfrp1 inhibits fibroblast invasion during transition to injury induced myofibroblasts - Tcf21 labeled mice

| PRJNA856687 | ENA

Cardiac transcriptome of Tcf21-depleted Xenopus embryos

Project description:The aim of the approach was to use RNAseq analysis to identify genes expressed in Xenopus epicardium that were affected by embryonic depletion of the epicardial transcription factor Tcf21 compared to control-MO injected siblings. Both upregulated and downregulated genes were validated by RT-PCR and whole embryo in situ hybridization to validate gene expression and assess spatio-temporal distribution of genes of interest within the heart and epicardium. Approximately 70-100 stage 44-46 Xenopus laevis hearts were dissected to isolate total mRNA from which poly-adenylated RNA was extracted using the Illumina standard protocol. This experiment represents one replicate from pooled hearts. mRNA profiles of stage 44-45 Xenopus laevis sibling hearts from control or Tcf21-depleted embryos, were generated by deep sequencing using Illumina GAII.

2013-07-05 | E-GEOD-45786 | biostudies-arrayexpress

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