Abstract:
:Regenerative therapy of the salivary gland (SG) is a promising therapeutic approach for irreversible hyposalivation in patients with head and neck cancer treated by radiotherapy. However, little is known about the molecular regulators of stem/progenitor cell activity and regenerative processes in the SG. Wnt/β-catenin signaling regulates the function of many adult stem cell populations, but its role in SG development and regeneration is unknown. Using BAT-gal Wnt reporter transgenic mice, we demonstrate that in the submandibular glands (SMGs) of newborn mice Wnt/β-catenin signaling is active in a few cells at the basal layer of intercalated ducts, the putative location of salivary gland stem/progenitor cells (SGPCs). Wnt activity decreases as mice age, but is markedly enhanced in SG ducts during regeneration of adult SMG after ligation of the main secretory duct. The Hedgehog (Hh) pathway is also activated after duct ligation. Inhibition of epithelial β-catenin signaling in young Keratin5-rtTA/tetO-Dkk1 mice impairs the postnatal development of SMG, particularly affecting maturation of granular convoluted tubules. Conversely, forced activation of epithelial β-catenin signaling in adult Keratin5-rtTA/tetO-Cre/Ctnnb1((Ex3)fl) mice promotes proliferation of ductal cells, expansion of the SGPC compartment, and ectopic activation of Hh signaling. Taken together, these results indicate that Wnt/β-catenin signaling regulates the activity of SGPCs during postnatal development and regeneration upstream of the Hh pathway, and suggest the potential of modulating Wnt/β-catenin and/or Hh pathways for functional restoration of SGs after irradiation.
journal_name
Stem Cells Devjournal_title
Stem cells and developmentauthors
Hai B,Yang Z,Millar SE,Choi YS,Taketo MM,Nagy A,Liu Fdoi
10.1089/scd.2009.0499subject
Has Abstractpub_date
2010-11-01 00:00:00pages
1793-801issue
11eissn
1547-3287issn
1557-8534journal_volume
19pub_type
杂志文章abstract::Heterotopic ossification (HO) is a common and debilitating complication of burns, traumatic brain injuries, and musculoskeletal trauma and surgery. Although the exact mechanism of ectopic bone formation is unknown, mesenchymal stem cells (MSCs) capable of osteogenic differentiation are known to play an essential role....
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0291
更新日期:2015-01-15 00:00:00
abstract::Stromal cells have been used to induce dopaminergic differentiation of mouse, primate, and human embryonic stem cells (hESCs), but the mechanism that governs this induction is unknown. In this manuscript, we show that medium conditioned by the stromal cell line PA6 (PA6-CM) can induce dopaminergic differentiation in n...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0107
更新日期:2010-01-01 00:00:00
abstract::Bone marrow human mesenchymal stem cells (hMSCs) are known to survive in serum-free media, when most normal somatic cells do not survive. We found that the endogenously-activated bone morphogenetic protein (BMP) pathway is involved in this cellular behavior. Under this culture condition, phosphorylated Smad1 (PSmad1),...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0020
更新日期:2009-11-01 00:00:00
abstract::Bone marrow (BM)-derived mesenchymal stromal cells (MSCs) frequently display alterations in several hematologic disorders, such as acute lymphoid leukemia, acute myeloid leukemia (AML), and myelodysplastic syndromes. In acute leukemias, it is not clear whether MSC alterations contribute to the development of the malig...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2016.0295
更新日期:2017-05-15 00:00:00
abstract::Here, we describe a focused microarray for screening rat embryonic stem cells (ESCs) and provide validation data that this array can distinguish undifferentiated rat ESCs from rat trophoblast stem (TS) cells, rat extraembryonic endoderm cells, mouse embryonic fibroblast feeder cells, and differentiated rat ESCs. Using...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0279
更新日期:2013-02-01 00:00:00
abstract::Embryonic stem (ES) cells give rise to mesodermal progenitors that differentiate to hematopoietic and cardiovascular cells. The wnt signaling pathway plays multiple roles in cardiovascular development through a network of intracellular effectors. To monitor global changes in wnt signaling during ES cell differentiatio...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0326
更新日期:2012-01-01 00:00:00
abstract::A comparative analysis of mouse and human pancreatic development may reveal common mechanisms that control key steps as organ morphogenesis and cell proliferation and differentiation. More specifically, understanding beta cell development remains an issue, despite recent progress related to their generation from human...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0550
更新日期:2015-08-01 00:00:00
abstract::Human embryonic stem cells (hESCs) exhibiting skewed X chromosome inactivation (XCI) have been reported. The copy number variations (CNVs), loss of heterozygosity (LOH), or single-nucleotide variant (SNV) events in those epigenetically distinct cells remain unknown, and whether such genetic abnormalities will influenc...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0463
更新日期:2015-08-01 00:00:00
abstract::Postnatal pancreas is a potential source for progenitor cells to generate endocrine β-cells for treating type 1 diabetes. However, it remains unclear whether young (1-week-old) pancreas harbors multipotent progenitors capable of differentiating into duct, acinar, and endocrine cells. Laminin is an extracellular matrix...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2015.0007
更新日期:2015-09-01 00:00:00
abstract::Human umbilical cord blood (CB) has been used successfully in stem cell transplantation. A subpopulation of CD34(+) cells expresses chemokine receptor CXCR4 which is critical for bone marrow engraftment in human hematopoietic stem cells. Here, we demonstrate the effect of short-term culture on CXCR4 expression on umbi...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2008.0298
更新日期:2009-10-01 00:00:00
abstract::Stem cell-based therapy is a promising treatment for neurodegenerative diseases. In our laboratory, a novel protocol has been developed to induce bone marrow-derived mesenchymal stem cells (MSC) into neurotrophic factors- secreting cells (NTF-SC), thus combining stem cell-based therapy with the NTF-based neuroprotecti...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2008.0411
更新日期:2009-10-01 00:00:00
abstract::Ossification of the posterior longitudinal ligament (OPLL) is characterized by ectopic OPLL. To date, the specific molecular pathogenesis of OPLL has not been clearly elucidated. In this study, bone marrow-derived mesenchymal stem cells obtained from healthy donors (HD-MSCs) and patients with OPLL (OPLL-MSCs) were cul...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2020.0117
更新日期:2020-12-01 00:00:00
abstract::Body axes and germ layers evolve at gastrulation, and in mammals are driven by many genes; however, what orchestrates the genetic pathways during gastrulation remains elusive. Previously, we presented evidence that microRNA-17 (miRNA-17) family members, miR-17-5p, miR-20a, miR-93, and miR-106a were differentially expr...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0051
更新日期:2015-02-01 00:00:00
abstract::Human embryonic stem (hES) cells, like other stem cells, have the capacity to self-renew without differentiation. Although hES cells can be differentiated to many different tissue types in vitro, clinical uses have not yet been realized from the study of hES cells. Anticipation that these cells would be immediately us...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/154732804323099172
更新日期:2004-06-01 00:00:00
abstract::Extraembryonic endoderm (XEN) cells are stem cell lines derived from primitive endoderm cells of inner cell mass in blastocysts. These cells have self-renewal properties and differentiate into visceral endoderm (VE) and parietal endoderm (PE) of the yolk sac. Recently, it has been reported that XEN cells can contribut...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2017.0026
更新日期:2017-08-01 00:00:00
abstract::Little is known about the effects of ionizing radiation on the earliest stages of embryonic development although it is well recognized that ionizing radiation is a natural part of our environment and further exposure may occur due to medical applications. The current study addresses this issue using D3 mouse embryonic...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2015.0260
更新日期:2016-01-15 00:00:00
abstract::Multipotent stem/progenitor cells from bone marrow stroma (mesenchymal stromal cells or MSCs) were previously shown to enhance proliferation and differentiation of neural stem cells (NSCs) in vivo, but the molecular basis of the effect was not defined. Here coculturing human MSCs (hMSCs) with rat NSCs (rNSCs) was foun...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0444
更新日期:2011-02-01 00:00:00
abstract::Human embryonic stem (hES) cells represent a potentially unlimited source of transplantable beta-cells for the treatment of diabetes. Here we describe a differentiation strategy that reproducibly directs HES3, an National Institutes of Health (NIH)-registered hES cell line, into cells of the pancreatic endocrine linea...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2007.0029
更新日期:2007-08-01 00:00:00
abstract::Balanced and precisely controlled processes between self-renewal and differentiation of hematopoietic stem cells (HSCs) into all blood lineages are critical for vertebrate definitive hematopoiesis. However, the molecular mechanisms underlying the maintenance and differentiation of HSCs have not been fully elucidated. ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0623
更新日期:2013-09-15 00:00:00
abstract::Multipotent skin-derived progenitors (SKPs) can be traced back to embryonic neural crest cells and are able to differentiate into both neural and mesodermal progeny in vitro. Neural stem cells (NSCs) are capable of self-renewing and can contribute to neuron and glia in the nervous system. Recently, we derived porcine ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0067
更新日期:2012-09-20 00:00:00
abstract::Multipotent mesenchymal stromal cells (MSCs) are more and more frequently used to treat orthopedic injuries in horses. However, these cells are limited in their expandability and differentiation capacity. Recently, the first equine-induced pluripotent stem cell (iPSC) lines were reported by us [ 1 ]. In vitro differen...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0409
更新日期:2016-01-01 00:00:00
abstract::In this retrospective study, 209 patients with malignant disease were analyzed for levels of T-cell receptor excision circles (TRECs) for the first 24 months after allogeneic stem cell transplantation. CD3(+) cells were separated by direct antibody-coupled magnetic beads, followed by DNA extraction according to a stan...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0588
更新日期:2014-07-15 00:00:00
abstract::Cyclooxygenase-2 (COX-2) inhibitors suppress bone repair and bone formation by suppressing angiogenesis as well as potentially interfering with osteoblast and osteoclast functions. In spite of these reports, there is a controversy over the exact effects of COX-2 inhibitors on bone formation processes itself. This work...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0393
更新日期:2010-10-01 00:00:00
abstract::Immunodeficient mice transplanted with human hematopoietic stem cells (HSCs) have been referred to as "Human Immune System" (HIS) mice and are a translational platform for studying human immune responses in vivo. Human HSC sources used in generating HIS mice include fetal liver (FL), umbilical cord blood (CB), and adu...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2017.0156
更新日期:2017-12-01 00:00:00
abstract::We have isolated a novel progenitor cell population from adult rat pancreatic ducts, termed pancreatic-derived progenitor cells (PDPCs). Here, we report the in vitro culture, selection, and characterization of Thy1.1-positive and Thy1.1-negative PDPC subpopulations. These cells exhibit bipotentiality for differentiati...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2008.0301
更新日期:2009-12-01 00:00:00
abstract::Mesenchymal stem cells (MSC) possess a range of immunomodulatory properties which they exert through soluble mediators and through direct cell-cell contact. Due to these immune regulatory properties, the safety and clinical efficacy of MSC treatment has been tested in a number of autoimmune disorders. In this review w...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2015.0008
更新日期:2015-09-15 00:00:00
abstract::The success rate of human embryonic stem cell (hESC) derivation depends on both culture conditions and embryo quality and is routinely determined by morphological criteria. However, high incidence of chromosomal abnormality even in high-grade cleavage embryos from in vitro fertilization (IVF) patients suggests that th...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0136
更新日期:2010-01-01 00:00:00
abstract::Although amniotic fluid cells can differentiate into several mesenchymal lineages and have been proposed as a valuable therapeutic cell source, their ability to undergo terminal neuronal differentiation remains a cause of controversy. The aim of this study was to investigate the neuronal differentiation ability of the...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0281
更新日期:2012-03-20 00:00:00
abstract::Cell-based gene therapy holds a great promise for the treatment of human malignancy. Among different cells, mesenchymal stem cells (MSCs) are emerging as valuable anti-cancer agents that have the potential to be used to treat a number of different cancer types. They have inherent migratory properties, which allow them...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2016.0120
更新日期:2016-10-01 00:00:00
abstract::We have previously isolated mesenchymal stromal cells (MSCs) from the tracheal aspirates of premature neonates with respiratory distress. Although isolation of MSCs correlates with the development of bronchopulmonary dysplasia, the physiologic role of these cells remains unclear. To address this, we further characteri...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2010.0494
更新日期:2011-11-01 00:00:00