The native extracellular matrix (ECM) provides a matrix to hold tissue/organ, defines the cellular fate and function, and retains growth factors. Such a matrix is considered as a most biomimetic scaffold for tissue engineering due to the biochemical and biological components, 3D hierarchical structure, and physicomechanical properties. Several attempts have been performed to decellularize allo- or

Osteoclastogenesis is induced by receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF), and can be suppressed by osteoprotegerin (OPG). Beclin1 has a dual role in osteoclastogenesis. However, the role of Beclin1-mediated autophagy during OPG-induced inhibition of osteoclastogenesis remains unclear. Here, we found that Beclin1 and matrix metalloproteinase

Retinoic acid (RA), an active metabolite of vitamin A, plays a critical role in the morphogenesis and differentiation of various tissues, especially in the central nervous system. RA is the most commonly used morphogen for the differentiation of human embryonic stem cells (hESCs) into neuronal progenitor cells (NPCs), an abundant source of healthy neuronal tissues for regenerative therapy. During the

Mouse penile development is androgen-dependent. During development of male and female external genitalia, an internal ectodermal epithelial structure forms called the preputial lamina. At puberty the male preputial lamina canalizes to create the preputial space, effectively splitting into two layers: (a) the epithelial lining of the prepuce and (b) the surface epithelium of the penis. The female preputial

Seminiferous tubules physically connect to the rete testis through short segments called the transition region (TR). During fetal development, this specialized junction is considered the initial site where testis cords begin to form and to grow in length well beyond birth and into adulthood and form convoluted tubular cores. Mitotic activity of the Sertoli cell, the somatic cell of the epithelium,

The liver is a complex organ composed of several cell types organized hierarchically. Among these, liver sinusoidal endothelial cells (LSECs) are specialized vascular cells known to interact with hepatocytes and hepatic stellate cells (HSCs), and to be involved in the regulation of important hepatic processes in healthy and pathological situations. Protocols for the differentiation of LSECs from human

Human mesenchymal stem cells (hMSCs) are multipotent cells that can be differentiated into different cell types including osteoblasts. Herein we aimed to assess the regulation of transcription factor mesenchyme homeobox 1 (Meox1) in the osteogenic differentiation of hMSCs and to determine the microRNA which targets on Meox1. Total RNA was extracted from the isolated ligamentum flavum tissue samples

Pluripotent stem cells (PSCs) are a promising source of endothelial cells (ECs) for the treatment of cardiovascular diseases. Since clinical application of embryo stem cells (ESCs) involves issues of medical ethics and risk of immune rejection, induced pluripotent stem cells (iPSCs) will facilitate cell transplantation therapy for the cardiovascular diseases. Swine is identified as an ideal large-animal

Tendon injuries are common and account for up to 50% of musculoskeletal injuries in the United States. The poor healing nature of the tendon is attributed to poor vascularization and cellular composition. In the absence of FDA-approved growth factors for tendon repair, engineering strategies using bioactive factors, donor cells, and delivery matrices to promote tendon repair and regeneration are being

A proper skin barrier function requires constant formation of stratum corneum, i.e. the outermost layer of epidermis composed of terminally differentiated keratinocytes. The complex process of converting proliferative basal keratinocytes into corneocytes relies on programmed changes in the activity of many well-established genes. Much remains however to be investigated about this process, e.g. in conjunction

Transcription factor p63 has critical functions in epidermal, hindgut/anorectal, and limb development. Human mutations in P63 correlate with congenital syndromes affecting the skin, anorectal, and limbs. Nevertheless, less are detected regarding networks and functions controlled by P63 mutations in dermal fibroblasts, which are closely related to skin physiology. To screen for new targets, we employed

Taxol (paclitaxel), a chemotherapeutic agent for several cancers, can adversely affect the peripheral nervous system. Recently, its negative impact on cognitive function in cancer patients has become evident. In rodents, taxol impaired learning and memory, with other possible negative effects on the brain. In this study, we investigated the effects of taxol on cultured neural stem cells (NSCs) from

The development of the female reproductive tract can be divided into three parts consisting of Müllerian duct organogenesis, pre-sexual maturation organ development, and post-sexual maturation hormonal regulation. In primates, Müllerian duct organogenesis proceeds in an estrogen independent fashion based on transcriptional pathways that are suppressed in males by the presence of AMH and SRY. However

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the authors, with the approval of the Editor-in-Chief. The journal was initially contacted by the corresponding author to report the unavailability of the raw data of the results presented by the

While estrogens are involved in normal prostate morphogenesis and function, inappropriate early-life estrogenic exposures, either in type, dose or timing, can reprogram the prostate gland and lead to increased disease risk with aging. This process is referred to as estrogen imprinting or developmental estrogenization of the prostate gland. The present review discusses published and new evidence for

Estrogen has always been considered the female hormone and testosterone the male hormone. However, estrogen's presence in the testis and deleterious effects of estrogen treatment during development have been known for nearly 90 years, long before estrogen receptors (ESRs) were discovered. Eventually it was learned that testes actually synthesize high levels of estradiol (E2) and sequester high concentrations

Estrogen signaling through the main estrogen receptor, estrogen receptor 1 (ESR1; also known as ERα), is essential for normal female and male reproductive function. Historically, studies of estrogen action have focused on the classical genomic pathway. Although this is clearly the major pathway for steroid hormone actions, these hormones also signal through rapid non-classical effects involving cell

This paper addresses a confusing issue of preputial anatomy of the mouse. The term “internal prepuce” was used in 2013 to describe a preputial structure integral to the mouse glans penis. Subsequently in 2015 the same term was applied by another group to describe entirely different morphology, generating confusion in the literature. Because it is inappropriate to use the same term to describe entirely

Osteoporosis is a systemic bone disease with bone fragility and increased fracture risk. The non-coding RNAs (ncRNAs) have appeared as important regulators of cellular signaling and pertinent human diseases. Studies have demonstrated that circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) are involved in the progression of osteoporosis through a variety of pathways, and are considered as targets

In the early 1960's, at Professor Bern's laboratory, University of California, Berkeley) in the US, Takasugi discovered ovary-independent, persistent vaginal changes in mice exposed neonatally to estrogen, which resulted in vaginal cancer later in life. Reproductive abnormalities in rodents were reported as a result of perinatal exposure to various estrogenic chemicals. Ten years later, vaginal cancers

Background Congenital hypospadias is a common congenital malformation of the urinary system in male children. However, the role of circRNA in congenital hypospadias remains unknown. Methods Differentially expressed circRNAs and mRNAs were identified by RNA sequencing. GO and KEEG analysis were performed to uncover the key function and pathways. The interaction networks were constructed and analyzed

This paper reviews and provides new observations on the ontogeny of estrogen receptor alpha (ESR1) and estrogen receptor beta (ESR2) in developing human male and female internal and external genitalia. Included in this study are observations on the human fetal uterine tube, the uterotubal junction, uterus, cervix, vagina, penis and clitoris. We also summarize and report on the ontogeny of estrogen

Osteogenic differentiation of dental pulp stem cells (DPSCs) is considered as a promising strategy in posterior maxilla tooth implantation. Information on the function and mechanisms of long non-coding RNAs (lncRNAs) in osteogenic differentiation of DPSCs is growing, however, the mechanism of LINC00968 and miR-3658 in regulating osteogenic differentiation of DPSCs still needs to be explored. In this

The Jost hypothesis states that androgens are necessary for normal development of the male external genitalia. In this review, we explore the complementary hypothesis that estrogens can elicit abnormal development of male external genitalia. Herein, we review available data in both humans and mice on the deleterious effects of estrogen on external genitalia development, especially during the “window

Adipogenesis has been extensively studied using in vitro models of cellular differentiation, enabling long-term regulation of fat cell metabolism in human adipose tissue (AT) material. Many studies promote the idea that manipulation of this process could potentially reduce the prevalence of obesity and its related diseases. It has now become essential to understand the molecular basis of fat cell development

Forkhead box (FOX) family transcription factors play essential roles in development, tissue homeostasis, and disease. Although the biology of several FOX proteins has been studied in depth, it is unclear to what extent these findings apply to even closely related family members, which frequently exert overlapping but non-redundant functions. To help address this question, we have generated a uniform

Hematopoietic stem cell-containing intra-aortic hematopoietic cell clusters (IAHCs) emerge in the dorsal aorta of the aorta-gonad-mesonephros (AGM) region during midgestation mouse embryos. We previously showed that transduction of Sox17 in CD45lowc-Kithigh cells, which are one component of IAHCs, maintained the cluster formation and the undifferentiated state, but the mechanism of the cluster formation

Fetal bovine serum (FBS) contains a large number of exosomes which may disturb the analysis of exosomes derived from cultured cells. We investigated the effect of FBS-derived exosomes (FBS-Exos) on the adipogenic differentiation of human bone marrow mesenchymal stromal cells (hBM-MSCs) and the underlying molecular mechanism. The uptake of FBS-Exos by hBM-MSCs could be detected by the laser confocal

The importance of oxygen tension in in vitro cultures and its effect on embryonic stem cell (ESC) differentiation has been widely acknowledged. Research has mainly focussed on ESC maintenance or on one line of differentiation and only few studies have examined the potential relation between oxygen tension during ESC maintenance and differentiation. In this study we investigated the influence of atmospheric

The goal of this paper is to explore the ability of the human female urogenital sinus immediately below the bladder (proximal urethra) to undergo prostatic development in response to dihydrotestosterone (DHT). To establish this idea, xenografts of human fetal female proximal urethra were grown in castrated nude mouse hosts receiving a subcutaneous DHT pellet. To verify the prostatic nature of the resultant

Osteoclasts are terminally multinucleated cells that are regulated by nuclear factor-activated T cells c1 (NFATc1), and are responsible for bone resorption while the tartrate resistant acid phosphatase (TRAP) enzymes releases into bone resorption lacunae. Furthermore, tumor suppressor p53 is a negative regulator during osteoclastogenesis. Osteoprotegerin (OPG) inhibits osteoclastogenesis and bone resorption

Differentiation of cultured skeletal myoblasts is induced by extrinsic signals that include reduction in ambient mitogen concentration and increased cell density. Using an established murine myoblast cell line (C2C12), we have found that experimental reduction of the nucleoporin p62 (Nup62) content of myoblasts enhances differentiation in high-mitogen medium, while forced expression of Nup62 inhibits

The capability to produce and maintain functional human adult hepatocytes remains one of the major challenges for the use of in-vitro models toward liver cell therapy and industrial drug-screening applications. Among the suggested strategies to solve this issue, the use of human-induced pluripotent stem cells (hiPSCs), differentiated toward hepatocyte-like cells (HLCs) is promising. In this work, we

Long noncoding RNAs (lncRNAs) have been shown to execute key roles in spermatogenesis. However, little is known about how lncRNAs gene expression is itself regulated in the germ cells of testis. We previously demonstrated that high expression of lncRNA-Gm2044 exists in spermatocytes and can regulate male germ cell proliferation. Here, the transcriptional regulation of lnRNA-Gm2044 expression in spermatocytes

Mesenchymal stromal/stem cells (MSCs) are attracting more and more attention due to their tissue regenerative properties and immunomodulatory functions. MSCs may be the most acceptable, safe, and effective source for allogeneic cell therapy, and have been used in medical treatment. However, the similarities and differences between umbilical cord-derived MSCs (UC-MSCs) of heterosexual twins remain poorly

Replicative senescence causes a reduced osteogenic differentiation potential of senescent dental follicle cells (DFCs). The transcription factor p53 is often involved in the induction of cellular senescence, but little is known about its role in DFCs. This study examined for the first time the role of p53 compared to its pro-proliferative antagonist E2F-1 in terms of osteogenic differentiation potential

Extracellular matrix (ECM) plays an integral role in different developmental stages and in multiple systems. However, due to ECM being composed of various extracellular components (growth factors, cytokines, and hormones), its innate complexity and the lack of any efficient purification techniques limit further research into the detailed mechanisms of its role in cellular activities. Laminin (LN),

Sea urchin development has been studied extensively for more than a century and considered regulative since the first experimental evidence. Further investigations have repeatedly supported this standpoint by revealing the presence of inductive mechanisms that alter cell fate decisions at early cleavage stages and flexibility of development in response to environmental conditions. Some features indicate

Thy-1 is a 25–37 kDa glycophosphatidylinositol (GPI)-anchored cell surface protein that was discovered more than 50 years ago. Recent findings have suggested that Thy-1 is expressed on thymocytes, mesenchymal stem cells (MSCs), cancer stem cells, hematopoietic stem cells, fibroblasts, myofibroblasts, endothelial cells, neuronal smooth muscle cells, and pan T cells. Thy-1 plays vital roles in cell migration

Laterality disease is frequently associated with congenital heart disease (CHD). However, it is unclear what is behind this association, a pleiotropic effect of common genetic causes of laterality diseases or the impact of abnormal left-right patterning on the downstream cardiovascular development. MEGF8 is a disease gene of Carpenter syndrome characterized by defective lateralization and CHD. Here

Circular RNAs (circRNAs) are a type of noncoding RNA (ncRNA) and have attracted widespread research attention in recent years. They form a covalently closed loop structure and are widely distributed in tissues and organs. CircRNAs have also been found to regulate a variety of biological processes by functioning as microRNA sponges, transcriptional regulators, and protein binding partners. Recent sequencing

The functional maturation of human pancreatic β-cells remains poorly understood. EndoC-βH2 is a human β-cell line with a reversible immortalized phenotype. Removal of the two oncogenes, SV40LT and hTERT introduced for its propagation, stops proliferation, triggers cell size increase and senescence, promotes mitochondrial activity and amplifies several β-cell traits and functions. Overall, these events

To induce and maintain naïve pluripotency in mouse embryonic and induced pluripotent stem cells (ESCs/iPSCs), chemically defined N2B27 medium with PD0325901, CHIR99021, and leukemia inhibitory factor (2i/LIF) is a classic and simple condition. However, this method cannot be simply extrapolated to human ESCs/iPSCs that are principally stabilized in primed pluripotency and become primitive neuroepithelium-like

Despite significant effort devoted to developing new treatments and procedures, cardiac disease is still one of the leading causes of death in the world. The loss of myocytes due to ischemic injury remains a major therapeutic challenge. However, cell-based therapy to repair the injured heart has shown significant promise in basic and translation research and in clinical trials. Embryonic stem cells

Background The periodontal ligament contains periodontal ligament cells, which is a heterogeneous cell population, and includes progenitor cells that can differentiate into osteoblasts/cementoblasts. Mesenchymal stem cells (MSCs) can differentiate into various cells and can be used for periodontal regenerative therapy. Therefore, transplanted MSCs can be affected by humoral factors from periodontal

Idiopathic pulmonary fibrosis (IPF) is a serious lung disease that involved the myofibroblast differentiation of lung resident mesenchymal stem cells (LR-MSCs). However, the specific molecular mechanisms of myofibroblast differentiation of LR-MSCs still remain a mystery. In this study, a comprehensive analysis of miRNAs and mRNAs changes in LR-MSCs treated with TGF-β1 was performed. Through computational

Human induced pluripotent stem cells (hiPSCs) are potentially an invaluable source of cells for regenerative medicine, disease modeling and drug discovery. However, the differentiation of hiPSCs into fully functional hepatocytes remains a major challenge. Despite the importance of the information carried by metabolomes, the exploitation of metabolomics for characterizing and understanding hiPSC differentiation

Defective anorectal and urogenital malformations are some of the most severe congenital anomalies encountered in children. Only a few molecular cues have been identified in early formation of the female urogenital system. Here we describe a novel long non-coding RNA molecule known as Leat1 (long non-coding RNA, EphrinB2 associated transcript 1). This lncRNA is syntenic with EfnB2 (which encodes EphrinB2)

To better understand how the human fetal penis and clitoris grows and remodels, we undertook an investigation to define active areas of cellular proliferation and programmed cell death spatially and temporally during development of human fetal external genitalia from the indifferent stage (8 weeks) to 18 weeks of gestation. Fifty normal human fetal penile and clitoral specimens were examined using

Fibroblast growth factor (FGF2) is reported to affect the proliferation, differentiation, and survival abilities of stem cells. In this study, we hypothesize that FGF2 might promote the differentiation of hair follicle stem cell (HFSCs) into endothelial cells (ECs), in a manner dependent on STAT5 activation. We first treated human HFSCs with recombinant human FGF2 to determine the involvement of FGF2

The exosomes from human exfoliated deciduous teeth (SHED-Exos) have exhibited potential therapeutic role in dental and oral disorders. The biological effects of exosomes largely depend on cellular origin and physiological status of donor cell. In the present study, we explored the influence of conditioned exosomes from SHED with osteogenic induction on periodontal ligament stem cells (PDLSCs) in vitro

Technological advances in three-dimensional (3D) reconstruction techniques have previously enabled paradigm shifts in our understanding of human embryonic and fetal development. Light sheet fluorescence microscopy (LSFM) is a recently-developed technique that uses thin planes of light to optically section whole-mount cleared and immunolabeled biologic specimens. The advent of commercially-available

Development of the human prepuce was studied over the course of 9–17 weeks of gestation in 30 specimens. Scanning electron microscopy revealed subtle surface features that were associated with preputial development, namely the appearance of epidermal aggregates that appeared to be associated with formation of the preputial fold. Transverse and sagittal sections revealed that the epidermis of the glans

During palatal development, medial edge epithelium (MEE) disappearance is one of the crucial steps in the process of fusion. The fate of these cells is still debated, and controversies remain. During secondary palate fusion, TGF-β3 signaling mediated in the cell through the SMAD2 protein plays an important role and leads to the disappearance of the midline epithelial seam (MES) and the confluence of

Cartilage tissue damage and diseases are the most common clinical situation that occurs because of aging and injury, thereby causing pain and loss of mobility. The inability of cartilage tissue to self-repair is instrumental in developing tissue engineered substitutes. To this effect, the present study aims to engineer cartilage construct by culturing umbilical cord blood-derived human mesenchymal

Development of external genitalia (ExG) has been a topic of long mystery in the field of organogenesis research. Early stage male and female of mouse embryos develop a common genital tubercle (GT) in the perineum whose outgrowth extends distally from the posterior cloacal regions. Concomitant with GT outgrowth, the cloaca is divided into urogenital sinus and anorectum by urorectal septum (URS) internally

Fertilization requires the physical combination of gametes, and terrestrial mammals necessitated the evolution of genitalia capable of successfully completing the fertilization process in a non-aqueous environment. Thus, the male mammalian external genitalia evolved as an outgrowth from the body, an appendage sufficient to fertilize eggs housed deep inside the female. In this way, sexual dimorphism

The goal of this report is (a) to provide the first detailed description of mouse clitoral development, and (b) to compare mouse and human clitoral development. For this purpose, external genitalia of female mice were examined by wholemount microscopy, histology and immunohistochemistry from 14 days of gestation to 10 days postnatal. Human clitoral development was examined by these techniques as well