Makoto Senoo

• Ph.D
• Professor (Associate) at Boston University

Mouse models have been used to study the physiology and pathogenesis of the skin. However, propagation of mouse primary epidermal keratinocytes remains challenging. In this chapter, we introduce a newly developed protocol that enables long-term expansion of p63+ mouse epidermal keratinocytes in low Ca2+ media without the need of progenitor cell-pur...

The co-culture of human epidermal keratinocytes with mouse 3T3-J2 feeder cells, a method developed by Green and colleagues, has been widely used since the early 1980s to generate skin autografts. Additionally, co-culture with 3T3-J2 cells has been a crucial tool in skin stem cell biology, as it facilitates the evaluation of self-renewal capacity an...

The surface of the middle ear is composed of the tympanic membrane (TM) and the middle ear mucosa (MEM). A number of diseases and conditions such as otitis media, middle ear cholesteatoma, and perforation of the TM have been reported to cause dysfunction of the middle ear, ultimately leading to high-frequency hearing loss. Despite its importance in...

Pancreatic cancer is a lethal malignancy with the highest mortality rate among all cancers and a 5-year survival rate of 9% in the US. Among all subtypes of pancreatic cancers, the molecular mechanisms underlying the development of squamous carcinomas are not well understood. While pure squamous carcinoma makes up only 0.05-5% of all pancreatic can...

Although mouse models have been used as an essential tool for studying the physiology and diseases of the skin, propagation of mouse primary epidermal keratinocytes remains challenging. In this chapter, we introduce the simplest, at least to our knowledge, protocol that enables long-term expansion of p63+ mouse epidermal keratinocytes in low Ca2+ m...

Co-culture of human epidermal keratinocytes with mouse 3T3-J2 feeder cells, developed by Green and colleagues, has been used worldwide to generate skin autografts since the early 1980s. In addition, co-culture with 3T3-J2 cells has served as a fundamental tool in skin stem cell biology as it allows the evaluation of self-renewal capacity of epiderm...

Mouse models have been used to study the physiology and pathogenesis of the skin. However, propagation of mouse primary epidermal keratinocytes remains challenging. In this chapter, we introduce a newly developed protocol that enables long-term expansion of p63⁺ mouse epidermal keratinocytes in low-Ca²⁺ media without the need of progenitor cell pur...

Mouse models have been used to provide primary cells to study physiology and pathogenesis of epithelia. However, highly efficient simple approaches to propagate mouse primary epithelial cells remain challenging. Here, we show that pharmacological inhibition of TGF-β signaling enables long-term expansion of p63⁺ epithelial progenitor cells in low Ca...

Cultured epidermal autografts have been used worldwide since 1981 for patients with extensive third-degree burn wounds and limited skin donor sites. Despite significant progress in techniques toward improving clinical outcome of skin grafts, the long in vitro preparation time of cultured autografts has remained a major factor limiting its widesprea...

Abbreviations: Dact1, dapper antagonist of β-catenin 1; HPEK, human primary epidermal keratinocyte; Igf, insulin-like growth factor; MEF, mouse embryonic fibroblast; TGF-β, transforming growth factor-β

The limited characterization of equine skin, eye and hoof epithelial stem cell (ESC) and differentiation markers impedes the investigation of the physiology and pathophysiology of these tissues. To characterize ESC and differentiation marker expression in epithelial tissues of the equine eye, haired skin and hoof capsule. Indirect immunofluorescenc...

The transcription factor p63 (Trp63) plays a key role in homeostasis and regeneration of the skin. The p63 gene is transcribed from dual promoters, generating TAp63 isoforms with growth suppressive functions and dominant-negative ΔNp63 isoforms with opposing properties. p63 also encodes multiple carboxy (C)-terminal variants. Although mutations of...

The skin interfollicular epidermis (IFE) is an organism's first line of defense against a harmful environment and physical damage. During homeostasis and wound repair, the IFE is rejuvenated constantly by IFE stem cells (SCs) that are capable of both proliferation and differentiation. However, the identity and behavior of IFE SCs remain controversi...

The transcription factor p63 plays an essential role in maintaining the proliferative potential of epidermal stem cells. We have shown recently that under homoeostatic conditions, phosphorylation of p63 increases during the early transition of stem cells to transit-amplifying cells in human epidermis. However, how p63 phosphorylation relates to the...

Background: Although Xenopus laevis has been a model of choice for comparative and developmental studies of the immune system, little is known about organogenesis of the thymus, a primary lymphoid organ in vertebrates. Here we examined the expression of three transcription factors that have been functionally associated with pharyngeal gland develo...

Bridging Stem Cell Research from Humans to Animals Translational stem cell research is a relatively young subspecialty of clinical research in animals. Although the success of therapeutic stem cell therapies in humans was based on research in small animal models, namely mice, development of clinical applications for farm and companion animals has b...

Abbreviations: CK14, cytokeratin-14; HPEK, human primary epidermal keratinocyte; SC, stem cell; TA, transit amplifying

Abnormal epidermal stem cell regulation may contribute to the pathogenesis of equine chronic laminitis. To analyse the involvement of p63, a regulator of epidermal stem cell proliferative potential, in chronic laminitis. Epidermal tissues from skin, coronet and lamellae of the dorsal foot were harvested from 5 horses with chronic laminitis and 5 co...

CHO administration or upon reaching Obel grade 3 lame-ness whichever occurred first. Horses in the treatment group received 8.5 mg/kg PTX in 1 L saline IV over 30 minutes beginning 12 hours prior to CHO administration, then every 12 hours thereafter until the completion of the study. MMP activity in the digital plasma will be evaluated using gelati...

The distinguishing feature of adult stem cells is their extraordinary capacity to divide prior to the onset of senescence. While stratified epithelia such as skin, prostate, and breast are highly regenerative and account disproportionately for human cancers, genes essential for the proliferative capacity of their stem cells remain unknown. Here we...

While studies of the adaptor SH3BP2 have implicated a role in receptor-mediated signaling in mast cells and lymphocytes, they have failed to identify its function or explain why SH3BP2 missense mutations cause bone loss and inflammation in patients with cherubism. We demonstrate that Sh3bp2 "cherubism" mice exhibit trabecular bone loss, TNF-alpha-d...

The recent discoveries of p63 and p73, homologs of the tumor suppressor p53, raised the possibility of a network of these family members governing cell cycle arrest and apoptosis in response to stress. However, mice lacking p73 show no tendency for spontaneous tumors, and mutations in p63 or p73 are rare in human tumors, rendering any obligate role...

Seventy percent of the murine TCRbeta locus (475 kb) was deleted to generate a large deleted TCRbeta (beta(LD)) allele to investigate a possible linkage between germline transcription, recombination frequency, and allelic exclusion of the TCR Vbeta genes. In these beta(LD/LD) mice, the TCRbeta gene locus contained only four Vbeta genes at the 5' si...

Histone acetylation is suggested to regulate gene expression in the TCR loci. Using R2CD3 mouse model, we previously showed that germline transcription of the TCRbeta chain gene is discrete between 5' Vbeta regions and Dbeta-Jbeta-Cbeta clusters plus Vbeta14 region. In this study, we investigated a role of histone H3 acetylation in transcriptional...

Tumor suppressor p53 has been shown to repress expression of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen and a key mediator of tumor angiogenesis. The p63 gene, recently identified as a p53-relative, encodes multiple isoforms with structural and functional similarities and differences from p53. In this study, we...

A novel cDNA-encoding polypeptide of 545 amino acid residues was identified from a mouse testis cDNA library. The transcript of this gene, p59(scr), was predominantly expressed in the testis and was developmentally regulated during spermatogenesis. The encoded protein was expressed in spermatocytes and round spermatids within seminiferous tubules o...

Tumor suppressor p53 has been shown to repress expression of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen and a key mediator of tumor angiogenesis. The p63 gene, recently identified as a p53-relative, encodes multiple isoforms with structural and functional similarities and differences from p53. In this study, we...

We have generated mutant mice in which TCR beta chain enhancer (E(beta)) was replaced with the TCR alpha chain enhancer (E(alpha)). Using this mouse model, we analyzed (i) recombination status of the TCR beta chain genes after functional V(D)J rearrangements occurred in the first allele during double-negative (DN)-to-double-positive (DP) transition...

Tumor suppressor p53 has been shown to transactivate epidermal growth factor receptor (EGFR) expression through binding to a putative p53 responsive element in the EGFR promoter between nucleotides -265 and -239 (EGFRp53RE). Isotypes of p63 gene products, recently identified as p53 relatives, have a similar function to transactivate several p53 tar...

We have generated mutant mice in which TCR β chain enhancer (E β) was replaced with the TCR α chain enhancer (E α). Using this mouse model, we analyzed (i) recombination status of the TCR β chain genes after functional V(D)J rearrangements occurred in the first allele during double-negative (DN)-to-double-positive (DP) transition and (ii) involveme...

The p51/p73L/p63/p40 gene, recently identified as a p53 homolog, encodes two major isoforms, p51A and p73L, which are suggested to have similar functions synonymous with p53 and dominant-negative activity toward both p53 and p51A, respectively. We have cloned a high affinity genomic fragment bound to p51A that was assigned to be a novel retrovirus...

We have recently identified a second p53 -related p73L gene, also referred to as p63 / p51 / p40 / KET gene, which encodes the 2 major isoforms p73L and p51 resulting from different exon usage at their amino terminal regions. Although p73L and p51 are suspected to play oncogenic and tumour suppressive roles in mammalian cells, respectively, no evid...

The p51/p73L/p63/p40 gene, recently identified as a p53 homolog, encodes two major isoforms, p51A and p73L, which are suggested to have similar functions synonymous with p53 and dominant-negative activity toward both p53 and p51A, respectively. We have cloned a high affinity genomic fragment bound to p51A that was assigned to be a novel retrovirus...

Genetic mutation of p53, which monitors DNA damage and operates cellular checkpoints, is a major factor in the development of human malignancies. A novel gene p63/p73L/p51, encoding a protein with significant homology to p53 and p73, was recently identified at 3q27-9. To investigate the penetration of p63 in cervical carcinogenesis, mutation and tr...

The p53 protein, which regulates the rate of cell division and death, is the most frequently mutated tumor suppressor to be identified so far in human cancers. Recently, a gene with significant homology to p53, termed p73, has been identified in a chromosomal region that is implicated in the molecular pathogenesis of neuroblastoma. We have cloned a...

During the thymic development of alphabeta lineage T cells, maturation of the CD4- CD8- double-negative (DN) cells into the CD4+ CD8+ double-positive cells is accompanied by the induction of TCR beta allelic exclusion. Recent studies have shown that these events are regulated by the signals through the pre-TCR complex which consists of the TCR beta...

On Aug 21, 1998 this sequence version replaced gi:3298108. Sequence updated (11-Jul-1998).