HNF4α and CDX2 Regulate Intestinal YAP1 Promoter Activity

Larsen, Sylvester; Davidsen, Johanne; Dahlgaard, Katja; Pedersen, Ole Birger; Troelsen, Jesper T.

doi:10.3390/ijms20122981

Cited by 11 publications

(6 citation statements)

References 53 publications

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“…1b, c), were likely the cells from developing gastrointestinal tract adjacent to the ventral wall of dorsal aorta. 59,60 WT1 + Mes was probably from the mesonephros tissues nearby the dorsal aorta. 61 The remaining three mesenchymal populations extensively expressed PDGFRA (Fig.…”

Section: Resultsmentioning

confidence: 99%

Tracing the first hematopoietic stem cell generation in human embryo by single-cell RNA sequencing

et al. 2019

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Tracing the emergence of the first hematopoietic stem cells (HSCs) in human embryos, particularly the scarce and transient precursors thereof, is so far challenging, largely due to the technical limitations and the material rarity. Here, using single-cell RNA sequencing, we constructed the first genome-scale gene expression landscape covering the entire course of endothelial-to-HSC transition during human embryogenesis. The transcriptomically defined HSC-primed hemogenic endothelial cells (HECs) were captured at Carnegie stage (CS) 12–14 in an unbiased way, showing an unambiguous feature of arterial endothelial cells (ECs) with the up-regulation of RUNX1, MYB and ANGPT1. Importantly, subcategorizing CD34+CD45− ECs into a CD44+ population strikingly enriched HECs by over 10-fold. We further mapped the developmental path from arterial ECs via HSC-primed HECs to hematopoietic stem progenitor cells, and revealed a distinct expression pattern of genes that were transiently over-represented upon the hemogenic fate choice of arterial ECs, including EMCN, PROCR and RUNX1T1. We also uncovered another temporally and molecularly distinct intra-embryonic HEC population, which was detected mainly at earlier CS 10 and lacked the arterial feature. Finally, we revealed the cellular components of the putative aortic niche and potential cellular interactions acting on the HSC-primed HECs. The cellular and molecular programs that underlie the generation of the first HSCs from HECs in human embryos, together with the ability to distinguish the HSC-primed HECs from others, will shed light on the strategies for the production of clinically useful HSCs from pluripotent stem cells.

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Section: Resultsmentioning

confidence: 99%

Tracing the first hematopoietic stem cell generation in human embryo by single-cell RNA sequencing

et al. 2019

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“…To investigate the role of CDX2 in cell adhesion, the colon cancer cell line LS174T with inducible CDX2 was used. This cell line has previously been used to study the effect of CDX2 on intestinal transcriptional regulation [36][37][38]. Western blotting analysis of the LS174T wild type and LS174T with inducible CDX2 cells was performed to detect CDX2 levels.…”

Section: Resultsmentioning

confidence: 99%

CDX2 expression and perioperative patient serum affects the adhesion properties of cultured colon cancer cells

et al. 2020

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Background: Colon cancer is one of the most commonly diagnosed types of cancer with surgical resection of the tumor being the primary choice of treatment. However, the surgical stress response induced during treatment may be related to a higher risk of recurrence. The aim of this study was to examine the effect of surgery on adhesion of cultured colon cancer cells with or without expression of the tumour suppressor CDX2. Method: We enrolled 30 patients undergoing elective, curatively intended laparoscopic surgery for colon cancer in this study. Blood samples were drawn 1 day prior to surgery and 24 h after surgery. The samples of pre-and postoperative serum was applied to wild type colon cancer LS174T cells and CDX2 inducible LS174T cells and adhesion was measured with Real-Time Cell-Analysis iCELLigence using electrical impedance as a readout to monitor changes in the cellular adhesion. Results: Adhesion abilities of wild type LS174T cells seeded in postoperative serum was significantly increased compared to cells seeded in preoperative serum. When seeding the CDX2 inducible LS174T cells without CDX2 expression in pre-and postoperative serum, no significant difference in adhesion was found. However, when inducing CDX2 expression in these cells, the adhesion abilities in pre-and postoperative serum resembled those of the LS174T wild type cell line. Conclusions: We found that the adhesion of colon cancer cells was significantly increased in postoperative versus preoperative serum, and that CDX2 expression affected the adhesive ability of cancer cells. The results of this study may help to elucidate the pro-metastatic mechanisms in the perioperative phase and the role of CDX2 in colon cancer metastasis.

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“…Incidentally, it has been reported that YAP1 can negatively regulate HNF4α expression through ubiquitination and proteasomal degradation in hepatocellular carcinoma (HCC) cells ( Cai et al, 2017 ). It is interesting to note that CDX2 and HNF4α regulate YAP1 expression by interacting with its promoter ( Larsen et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Src family kinases inhibit differentiation of intestinal epithelial cells through the Hippo effector YAP1

Fallah

Beaulieu

2021

Biology Open

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Intestinal cell lineage differentiation is a tightly regulated mechanism that involves several intracellular signaling pathways affecting the expression of a variety of transcription factors, which ultimately regulate cell specific gene expression. Absorptive and goblet cells are the two main epithelial cell types of the intestine. Previous studies from our group using an shRNA knockdown approach have shown that YAP1, one of the main Hippo pathway effectors, inhibits the differentiation of these two cell types. In the present study, we show that YAP1 activity is regulated by Src family kinases (SFKs) in these cells. Inhibition of SFKs led to a sharp reduction in YAP1 expression at the protein level, an increase in CDX2 and the P1 forms of HNF4α and of absorptive and goblet cell differentiation specific markers. Interestingly, in Caco-2/15 cells which express both YAP1 and its paralog TAZ, TAZ was not reduced by the inhibition of SFKs and its specific knockdown rather impaired absorptive cell differentiation indicating that YAP1 and TAZ are not always interchangeable for regulating cell functions.

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HNF4α and CDX2 Regulate Intestinal YAP1 Promoter Activity

Cited by 11 publications

References 53 publications

Tracing the first hematopoietic stem cell generation in human embryo by single-cell RNA sequencing

Tracing the first hematopoietic stem cell generation in human embryo by single-cell RNA sequencing

CDX2 expression and perioperative patient serum affects the adhesion properties of cultured colon cancer cells

Src family kinases inhibit differentiation of intestinal epithelial cells through the Hippo effector YAP1

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