Abstract:
:In the seminiferous epithelium of the testis, Sertoli cells are key niche cells directing proliferation and differentiation of spermatogonial stem cells (SSCs) into spermatozoa. Sertoli cells produce glial cell line-derived neurotrophic factor (GDNF), which is essential for SSC self-renewal and progenitor expansion. While the role of GDNF in the testis stem cell niche is established, little is known about how this factor is regulated. Our previous studies on NOTCH activity in Sertoli cells demonstrated a role of this pathway in limiting stem/progenitor cell numbers, thus ultimately downregulating sperm cell output. In this study we demonstrate through a double-mutant mouse model that NOTCH signaling in Sertoli cells functions solely through the canonical pathway. Further, we demonstrate through Dual luciferase assay and chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR) analysis that the NOTCH targets HES1 and HEY1, which are transcriptional repressors, directly downregulate GDNF expression by binding to the Gdnf promoter, thus antagonizing the effects of FSH/cAMP. Finally, we demonstrate that testicular stem/progenitors cells are activating NOTCH signaling in Sertoli cells in vivo and in vitro through the NOTCH ligand JAG1 at their surface, indicating that these cells may ensure their own homeostasis through negative feedback regulation.
journal_name
Stem Cells Devjournal_title
Stem cells and developmentauthors
Garcia TX,Parekh P,Gandhi P,Sinha K,Hofmann MCdoi
10.1089/scd.2016.0318subject
Has Abstractpub_date
2017-04-15 00:00:00pages
585-598issue
8eissn
1547-3287issn
1557-8534journal_volume
26pub_type
杂志文章abstract::Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming ne...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0451
更新日期:2013-05-15 00:00:00
abstract::The mechanisms responsible for the inhibitory effects of mesenchymal stem cells (MSCs) on dendritic cells (DCs) are still poorly understood. Our investigation of the potential signaling pathways revealed for the first time that human umbilical-cord-derived MSCs (UC-MSCs) instruct DCs to acquire tolerogenic phenotypes ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0559
更新日期:2014-09-01 00:00:00
abstract::Remyelination is the goal of potential cell transplantation therapies for demyelinating diseases and other central nervous system injuries. Transplantation of oligodendrocyte precursor cells (OPCs) can result in remyelination in the central nervous system, and induced pluripotent stem cells (iPSCs) are envisioned to b...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2015.0244
更新日期:2016-05-01 00:00:00
abstract::Phenotypic guidance of embryonic stem (ES) cell fate is paramount if these cells are to be used for tissue repair and regeneration. Our objective was to compare two different cell culture feeders and their effect on proliferation, apoptosis, and differentiation of human (h) ES cells. HSF-6 hES cells were grown in Knoc...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2006.0109
更新日期:2007-06-01 00:00:00
abstract::Pluripotent stem cell-derived endothelial cells (ECs) have great potential to be used in vascular therapy or tissue engineering. It is also much desired to obtain arterial or venous ECs for specific applications. Factors that are critical for the proper arterial or venous differentiation from pluripotent stem cells st...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2017.0240
更新日期:2018-04-01 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::Mesenchymal stem cells (MSCs) from bone marrow (BM) are widely used for bone and less for cartilage tissue regeneration due to their self-renewal and differentiating properties into osteogenic or chondrogenic lineages. This review considers the last decade of clinical trials involving a two-step procedure, by expandin...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2012.0373
更新日期:2013-01-15 00:00:00
abstract::Transcription factor FoxA1 plays a critical role during embryonic development and is activated during retinoic acid (RA)-induced neural differentiation of pluripotent P19 embryonal carcinoma cells at the early stage, which is marked by decreased expression of Nanog and increased expression of neural stem cell marker N...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0386
更新日期:2010-09-01 00:00:00
abstract::Diseases of the digestive tract are complex and encompass a broad spectrum of different pathogeneses (inflammatory, ischemic, neoplastic, and functional deficit). The digestive tract is not a sterile environment, and its organs are composed of tissues with different embryologic origin and different morphologic and fun...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2010.0277
更新日期:2011-07-01 00:00:00
abstract::Fluorescence in situ hybridization (FISH) was used to analyze peripheral blood stem cells (PBSC) and stem cell assays (SCA) derived from them in 2 patients with acute myeloid leukemia (AML) with trisomy 8 as the sole chromosome abnormality prior to undergoing autologous stem cell transplantation. In both cases, the de...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/154732804773099227
更新日期:2004-02-01 00:00:00
abstract::Immune suppression is a very stable property of multipotent stromal cells also known as mesenchymal stem cells (MSCs). All cell lines tested showed robust immune suppression not affected by a long culture history. Several mechanisms were described to account for this capability. Since several of the described mechanis...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0433
更新日期:2014-07-15 00:00:00
abstract::Aneurysm refers to the dilation of the vessel wall for more than 50%. Abdominal aortic aneurysm (AAA) refers to the dilation and weakening of all three layers of the abdominal aorta, which mostly occur infrarenally. The population aged above 50 years is at risk of AAA development, while a familiar history doubles the ...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2014.0517
更新日期:2015-07-01 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::There have been reports of marrow cells converting into pulmonary epithelial cells after marrow transplantation in irradiated mice. We evaluated the impact of whole bone marrow (WBM) infusion in mice, with or without total body irradiation (TBI), treated with saline or monocrotaline (MCT), which induces pulmonary hype...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2008.0237
更新日期:2009-06-01 00:00:00
abstract::The induction and detection of chemotactic migration in mesenchymal stem cells (MSC) are complicated by their adherent nature. We describe here the experimental details for inducing the transmigration of MSC seeded in microchemotaxis chambers and reliably identifying the translocated cells. A combination of 8-microm p...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2005.14.231
更新日期:2005-04-01 00:00:00
abstract::In a previous study we established colony assays suitable for studying murine adult (2-4 months) pancreatic progenitor cells plated in semisolid media containing methylcellulose and extracellular matrix proteins. Using these assays, we found robust in vitro progenitor cell activities (multilineage differentiation and ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0466
更新日期:2014-04-15 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::Retinoic acid (RA) is present at sites of neurogenesis in both the embryonic and adult brain. While it is widely accepted that RA signaling is involved in the regulation of neural stem cell differentiation, little is known about vitamin A utilization and biosynthesis of active retinoids in the neurogenic niches, or ab...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0422
更新日期:2013-10-15 00:00:00
abstract::Regenerative medicine is in demand of adult pluripotent stem cells (PSCs). The "Bonghan System (BHS)" was discovered and suggested to contain cells with regenerative capacity in the early 1960s. It had been ignored for a long time due to the lack of sufficient details of experiments, but about 37 years after the initi...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2015.0024
更新日期:2015-10-01 00:00:00
abstract::Nonpluripotent neural progenitor cells (NPCs) derived from the human fetal central nervous system were found to express a number of messenger RNA (mRNA) species associated with pluripotency, such as NANOG, REX1, and OCT4. The expression was restricted to small subpopulations of NPCs. In contrast to pluripotent stem ce...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2016.0346
更新日期:2017-06-15 00:00:00
abstract::The capability to form all cell types of the body is a unique feature of stem cells. However, many questions remain concerning the mechanisms regulating differentiation potential. The derivation of spermatogonial cell lines (SGs) from mouse and human, which can differentiate across germ-layer borders, suggested male g...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2010.0290
更新日期:2011-08-01 00:00:00
abstract::Osteogenesis imperfecta (OI) is a genetic bone pathology with prenatal onset, characterized by brittle bones in response to abnormal collagen composition. There is presently no cure for OI. We previously showed that human first trimester fetal blood mesenchymal stem cells (MSCs) transplanted into a murine OI model (oi...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0132
更新日期:2014-02-01 00:00:00
abstract::Osteophytes are a distinct feature of osteoarthritis (OA). Their formation may be related to pluripotential cells in the periosteum responding to stimulus during OA. This study aimed to isolate stem cells from osteophyte tissues and to characterize their phenotype, proliferation, and differentiation potential, as well...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2007.0146
更新日期:2008-04-01 00:00:00
abstract::Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a severe adverse reaction, which results in progressive bone destruction in the maxillofacial region of patients. To date, the pathological mechanisms remain largely unclear. Recently, we found that BRONJ patient had significantly deep periodontal pockets and...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2019.0151
更新日期:2020-02-01 00:00:00
abstract::Human embryonic stem cells (hESCs) have the potential to differentiate into many adult cell types, and they are being explored as a resource for cell replacement therapies for multiple diseases. In order to optimize in vitro differentiation protocols, it will be necessary to elucidate regulatory mechanisms that contri...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0224
更新日期:2010-06-01 00:00:00
abstract::The optimization of defined growth conditions is necessary for the development of clinical application of human embryonic stem cells (hESCs). Current research has focused on developing defined media formulations for long-term culture of hESCs with little attention on the establishment of defined substrates for hESC pr...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2008.0410
更新日期:2009-10-01 00:00:00
abstract::In recent years it has been hypothesized that cancer stem cells (CSCs) are the actual driving force of tumor formation, highlighting the need to specifically target CSCs to successfully eradicate cancer growth and recurrence. Particularly, the deregulation of physiological signaling pathways controlling stem cell prol...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2015.0081
更新日期:2015-10-15 00:00:00
abstract::Bronchopulmonary dysplasia (BPD), the main complication of extreme prematurity, has lifelong consequences for lung health. Mesenchymal stromal cells (MSCs) prevent lung injury in experimental BPD in newborn rodents when given in the immediate neonatal period. Whether MSC therapy can restore normal lung growth after es...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2019.0116
更新日期:2020-03-15 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
abstract::Myocardial infarction (MI) results in loss of myofibers in the ischemic zone of the heart, followed by scar formation. These factors increase barriers to mobilization of mesenchymal stem cells (MSC), thereby impeding their effectiveness in cardiac repair. This study examined MSC overexpressing CXCR4 (MSC(CX4)) to dete...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0126
更新日期:2012-03-20 00:00:00