Foxp1 is an essential transcriptional regulator for the generation of quiescent naive T cells during thymocyte development

Feng, Xiaoming; Ippolito, Gregory C.; Tian, Lifeng; Wiehagen, Karla R.; Oh, Soyoung; Sambandam, Arivazhagan; Willen, Jessica; Bunte, Ralph M.; Maika, Shanna D.; Harriss, June V.; Caton, Andrew J.; Bhandoola, Avinash; Tucker, Philip W.; Hu, Hui

doi:10.1182/blood-2009-07-232694

Cited by 112 publications

(136 citation statements)

References 50 publications

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“…The forkhead transcription factor Foxp1 regulates many different developmental processes, from spinal cord, lung and heart to B and T cell development (Wang et al, 2004;Hu et al, 2006;Shu et al, 2007;Dasen et al, 2008;Feng et al, 2010;Zhang et al, 2010;Feng et al, 2011;Li et al, 2012). In this study, we show that Foxp1 is essential for the maintenance of the quiescent state of HFSCs.…”

Section: Discussionmentioning

confidence: 67%

“…(Wang et al, 2004). Similarly, loss of Foxp1 leads to the loss of quiescence in thymocytes and naive mature T cells (Feng et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Ablation of Foxp1 disrupts B cell development (Hu et al, 2006) as well as development of the lung and esophagus (Shu et al, 2007). Loss of Foxp1 increases proliferation of cardiomyocytes (Wang et al, 2004;Zhang et al, 2010) and disrupts the maintenance of the quiescent state of naive T cells (Feng et al, 2010;Feng et al, 2011). Foxp1 is also a suspected tumor suppressor, as its expression is reduced in a variety of tumors (Banham et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…Known to act as both a transcriptional repressor and activator, Foxp1 regulates the development of many tissues, including esophagus, lung, heart, thymus and spinal cord (Wang et al, 2004;Hu et al, 2006;Shu et al, 2007;Dasen et al, 2008;Feng et al, 2010;Zhang et al, 2010;Feng et al, 2011;Li et al, 2012). Ablation of Foxp1 disrupts B cell development (Hu et al, 2006) as well as development of the lung and esophagus (Shu et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Foxp1 maintains hair follicle stem cell quiescence through regulation of Fgf18

et al. 2013

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SUMMARYHair follicles cyclically degenerate and regenerate throughout adult life and require regular stem cell activation to drive the cycle. In the resting phase of the hair cycle, hair follicle stem cells are maintained in a quiescent state until they receive signals to proliferate. We found that the forkhead transcription factor Foxp1 is crucial for maintaining the quiescence of hair follicle stem cells. Loss of Foxp1 in skin epithelial cells leads to precocious stem cell activation, resulting in drastic shortening of the quiescent phase of the hair cycle. Conversely, overexpression of Foxp1 in keratinocytes prevents cell proliferation by promoting cell cycle arrest. Finally, through both gain-and loss-of-function studies, we identify fibroblast growth factor 18 (Fgf18) as the key downstream target of Foxp1. We show that exogenously supplied FGF18 can prevent the hair follicle stem cells of Foxp1 null mice from being prematurely activated. As Fgf18 controls the length of the quiescent phase and is a key downstream target of Foxp1, our data strongly suggest that Foxp1 regulates the quiescent stem cell state in the hair follicle stem cell niche by controlling Fgf18 expression.

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Section: Discussionmentioning

confidence: 67%

“…(Wang et al, 2004). Similarly, loss of Foxp1 leads to the loss of quiescence in thymocytes and naive mature T cells (Feng et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Foxp1 maintains hair follicle stem cell quiescence through regulation of Fgf18

et al. 2013

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“…Shh-cre and Foxp1 flox/flox mice were previously generated and genotyped as described (Harfe et al, 2004;Feng et al, 2010). Foxp4 flox/+ mice were generated by introducing two loxP sites that flank exons 12 and13 coding the forkhead DNA-binding domain (supplementary material Fig.…”

Section: Animalsmentioning

confidence: 99%

Foxp1/4 control epithelial cell fate during lung development and regeneration through regulation of anterior gradient 2

Wang

Zhang

et al. 2012

Development

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SUMMARYThe molecular pathways regulating cell lineage determination and regeneration in epithelial tissues are poorly understood. The secretory epithelium of the lung is required for production of mucus to help protect the lung against environmental insults, including pathogens and pollution, that can lead to debilitating diseases such as asthma and chronic obstructive pulmonary disease. We show that the transcription factors Foxp1 and Foxp4 act cooperatively to regulate lung secretory epithelial cell fate and regeneration by directly restricting the goblet cell lineage program. Loss of Foxp1/4 in the developing lung and in postnatal secretory epithelium leads to ectopic activation of the goblet cell fate program, in part, through de-repression of the protein disulfide isomerase anterior gradient 2 (Agr2). Forced expression of Agr2 is sufficient to promote the goblet cell fate in the developing airway epithelium. Finally, in a model of lung secretory cell injury and regeneration, we show that loss of Foxp1/4 leads to catastrophic loss of airway epithelial regeneration due to default differentiation of secretory cells into the goblet cell lineage. These data demonstrate the importance of Foxp1/4 in restricting cell fate choices during development and regeneration, thereby providing the proper balance of functional epithelial lineages in the lung.

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FOXP1 enhances tumor cell migration by repression of NFAT1 transcriptional activity in MDA‐MB‐231 cells

Halaçlı

2016

Cell Biology International

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Until now, forkhead box P1 (FOXP1) has been identified as a tumor suppressor in several correlation studies in breast cancer. Although FOXP1 is defined as a transcriptional repressor that interacts with other transcription factors in various mechanistic studies, there is no study that explains its repressor functions in breast cancer biology. This study demonstrated the repressor function of FOXP1 on nuclear factor of activated T cells (NFAT1) and the migratory effect of this repression in MDA-MB-231 breast cancer cells. Co-immunoprecipitation experiments were performed for the investigation of protein-protein interaction between two transcription factors. Protein-protein interaction on DNA was investigated with EMSA and transcriptional effects of FOXP1 on NFAT1, luciferase reporter assay was performed. Wound healing assay was used to analyze the effects of overexpression of FOXP1 on tumor cell migration. This study showed that FOXP1 has protein-protein interaction with NFAT1 on DNA and enhances breast cancer cell migration by repressing NFAT1 transcriptional activity and FOXP1 shows oncogenic function by regulating breast cancer cell motility.

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Foxp1 is an essential transcriptional regulator for the generation of quiescent naive T cells during thymocyte development

Cited by 112 publications

References 50 publications

Foxp1 maintains hair follicle stem cell quiescence through regulation of Fgf18

Foxp1 maintains hair follicle stem cell quiescence through regulation of Fgf18

Foxp1/4 control epithelial cell fate during lung development and regeneration through regulation of anterior gradient 2

FOXP1 enhances tumor cell migration by repression of NFAT1 transcriptional activity in MDA‐MB‐231 cells

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