Foxm1 regulates cardiomyocyte proliferation in adult zebrafish after cardiac injury

Zuppo, Daniel A.; Missinato, Maria A.; Santana-Santos, Lucas; Li, Guang; Benos, Panayiotis V.; Tsang, Michael

doi:10.1242/dev.201163

Cited by 13 publications

(10 citation statements)

References 94 publications

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“… 61 Recently, Foxm1 has also been shown to promote cardiomyocyte proliferation in the zebrafish heart. 62 …”

Section: Discussionmentioning

confidence: 99%

Cell-Cycle–Specific Autoencoding Improves Cluster Analysis of Cycling Cardiomyocytes

Nguyen,

Nakada,

et al. 2024

Stem Cells

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Background Our previous analyses of cardiomyocyte single-nucleus RNA sequencing (snRNAseq) data from the hearts of fetal pigs and pigs that underwent apical resection surgery on postnatal day (P) 1 (ARP1), myocardial infarction (MI) surgery on P28 (MIP28), both ARP1 and MIP28 (ARP1MIP28), or controls (no surgical procedure or CTL) identified 10 cardiomyocyte subpopulations (clusters), one of which appeared to be primed to proliferate in response to MI. However, the clusters composed of primarily proliferating cardiomyocytes still contained non-cycling cells, and we were unable to distinguish between cardiomyocytes in different phases of the cell cycle. Here, we improved the precision of our assessments by conducting similar analyses with snRNAseq data for only the 1646 genes included under the Gene Ontology term "cell cycle." Methods Two cardiac snRNAseq datasets, one from mice (GEO dataset number GSE130699) and one from pigs (GEO dataset number GSE185289), were evaluated via our cell-cycle–specific analytical pipeline. Cycling cells were identified via the co-expression of five proliferation markers (AURKB, MKI67, INCENP, CDCA8, and BIRC5). Results The cell-cycle–specific autoencoder (CSA) algorithm identified seven cardiomyocyte clusters in mouse hearts (mCM1 and mCM3-mCM8), including one prominent cluster of cycling cardiomyocytes in animals that underwent MI or Sham surgery on P1. Five cardiomyocyte clusters (pCM1, pCM3-pCM6) were identified in pig hearts, two of which (pCM1 and pCM4) displayed evidence of cell cycle activity; pCM4 was found primarily in hearts from fetal pigs, while pCM1 comprised a small proportion of cardiomyocytes in both fetal hearts and hearts from ARP1MIP28 pigs during the two weeks after MI induction, but was nearly undetectable in all other experimental groups and at all other time points. Furthermore, pseudotime trajectory analysis of snRNAseq data from fetal pig cardiomyocytes identified a pathway that began at pCM3, passed through pCM2, and ended at pCM1, and whereas pCM3 was enriched for the expression of a cell-cycle activator that regulates the G1/S phase transition (Cyclin D2), pCM2 was enriched for an S-phase regulator (CCNE2), and pCM1 was enriched for the expression of a gene that regulates the G2M phase transition and mitosis (Cyclin B2). We also identified four transcription factors (E2F8, FOXM1, GLI3, and RAD51) that were more abundantly expressed in cardiomyocytes from regenerative mouse hearts than from nonregenerative mouse hearts, from the hearts of fetal pigs than from CTL pig hearts, and from ARP1MIP28 pig hearts than from MIP28 pig hearts during the two weeks after MI induction. Conclusions The CSA algorithm improved the precision of our assessments of cell cycle activity in cardiomyocyte subpopulations and enabled us to identify a trajectory across three clusters that appeared to track the onset and progression of cell-cycle activity in cardiomyocytes from fetal pigs.

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“… 61 Recently, Foxm1 has also been shown to promote cardiomyocyte proliferation in the zebrafish heart. 62 …”

Section: Discussionmentioning

confidence: 99%

Cell-Cycle–Specific Autoencoding Improves Cluster Analysis of Cycling Cardiomyocytes

Nguyen,

Nakada,

et al. 2024

Stem Cells

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“…FOXM1 can regulate cardiomyocyte proliferation and thus affect cardiomyocyte survival and function. During zebrafish heart regeneration following injury, Foxm1 is required in cardiomyocyte proliferation through transcriptional regulation of cell cycle genes ( 32 ). FOXM1 regulates biological processes such as cardiac fibrosis and inflammatory responses, accelerating the deterioration of cardiac function ( 11 ).…”

Section: Foxm1 In Regulating the Development And Progression Of Diabe...mentioning

confidence: 99%

“…FOXM1 also serves an important role in development of diabetes and its complications ( 9 - 31 ). FOXM1 is involved in regulating the cell cycle, promoting cell proliferation, maintaining normal cellular differentiation and DNA damage repair ( 11 , 12 , 32 ). In addition, FOXM1 may be involved in regulating onset and progression of diabetic complications, such as cardiovascular disease and nephropathy ( 13 , 33 ).…”

Section: Introductionmentioning

confidence: 99%

Role of transcription factor FOXM1 in diabetes and its complications (Review)

Zhao,

Li,

et al. 2023

Int J Mol Med

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Diabetes mellitus is a chronic metabolic disease commonly associated with complications such as cardiovascular disease, nephropathy and neuropathy, the incidence of which is increasing yearly. Transcription factor forkhead box M1 (FOXM1) serves an important role in development of diabetes and its complications. The present study aimed to review the association between FOXM1 with pathogenesis of diabetes and its complications. FOXM1 may be involved in development and progression of diabetes and its complications by regulating cell biological processes such as cell cycle, DNA damage repair, cell differentiation and epithelial-mesenchymal transition. FOXM1 is involved in regulation of insulin secretion and insulin resistance, and FOXM1 affects insulin secretion by regulating expression of insulin-related genes and signaling pathways; FOXM1 is involved in the inflammatory response in diabetes, and FOXM1 can regulate key genes associated with inflammatory response and immune cells, which in turn affects occurrence and development of the inflammatory response; finally, FOXM1 is involved in the regulation of diabetic complications such as cardiovascular disease, nephropathy and neuropathy. In summary, the transcription factor FOXM1 serves an important role in development of diabetes and its complications. Future studies should explore the mechanism of FOXM1 in diabetes and find new targets of FOXM1 as a potential treatment for diabetes and its complications.

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“…Forkhead box proteins constitute an evolutionarily conserved family of transcriptional regulators. Among them, forkhead box M1 (FOXM1) is known to be expressed in proliferating cells and associated with the activation of the mitotic programme 10 . FOXM1 plays a crucial role in cancer progression, influencing various steps such as epithelial–mesenchymal transition (EMT), cell proliferation, migration and premetastatic niche formation 11–13 .…”

Section: Introductionmentioning

confidence: 99%

“…Among them, forkhead box M1 (FOXM1) is known to be expressed in proliferating cells and associated with the activation of the mitotic programme. 10 FOXM1 plays a crucial role in cancer progression, influencing various steps such as epithelial–mesenchymal transition (EMT), cell proliferation, migration and premetastatic niche formation. 11 , 12 , 13 In the context of HCC, FOXM1 has been found to be upregulated and contributes to the progression of HCC by directly regulating the expression of KIF4A.…”

Section: Introductionmentioning

confidence: 99%

β‐Sitosterol suppresses hepatocellular carcinoma growth and metastasis via FOXM1‐regulated Wnt/β‐catenin pathway

Chen,

Yang,

Wang

et al. 2023

J Cellular Molecular Medi

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Abstractβ‐Sitosterol is a natural compound with demonstrated anti‐cancer properties against various cancers. However, its effects on hepatocellular carcinoma (HCC) and the underlying mechanisms are not well understood. This study aims to investigate the impact of β‐sitosterol on HCC. In this study, we investigated the effects of β‐sitosterol on HCC tumour growth and metastasis using a xenograft mouse model and a range of molecular analyses, including bioinformatics, real‐time PCR, western blotting, lentivirus transfection, CCK8, scratch and transwell assays. The results found that β‐sitosterol significantly inhibits HepG2 cell proliferation, migration and invasion both in vitro and in vivo. Bioinformatics analysis identifies forkhead box M1 (FOXM1) as a potential target for β‐sitosterol in HCC treatment. FOXM1 is upregulated in HCC tissues and cell lines, correlating with poor prognosis in patients. β‐Sitosterol downregulates FOXM1 expression in vitro and in vivo. FOXM1 overexpression mitigates β‐sitosterol's inhibitory effects on HepG2 cells. Additionally, β‐sitosterol suppresses epithelial–mesenchymal transition (EMT) in HepG2 cells, while FOXM1 overexpression promotes EMT. Mechanistically, β‐sitosterol inhibits Wnt/β‐catenin signalling by downregulating FOXM1, regulating target gene transcription related to HepG2 cell proliferation and metastasis. β‐Sitosterol shows promising potential as a therapeutic candidate for inhibiting HCC growth and metastasis through FOXM1 downregulation and Wnt/β‐catenin signalling inhibition.

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Foxm1 regulates cardiomyocyte proliferation in adult zebrafish after cardiac injury

Cited by 13 publications

References 94 publications

Cell-Cycle–Specific Autoencoding Improves Cluster Analysis of Cycling Cardiomyocytes

Cell-Cycle–Specific Autoencoding Improves Cluster Analysis of Cycling Cardiomyocytes

Role of transcription factor FOXM1 in diabetes and its complications (Review)

β‐Sitosterol suppresses hepatocellular carcinoma growth and metastasis via FOXM1‐regulated Wnt/β‐catenin pathway

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