scholarly journals FGF10 maintains stem cell compartment in developing mouse incisors

Development ◽  
2002 ◽  
Vol 129 (6) ◽  
pp. 1533-1541 ◽  
Author(s):  
Hidemitsu Harada ◽  
Takashi Toyono ◽  
Kuniaki Toyoshima ◽  
Masahiro Yamasaki ◽  
Nobuyuki Itoh ◽  
...  

Mouse incisors are regenerative tissues that grow continuously throughout life. The renewal of dental epithelium-producing enamel matrix and/or induction of dentin formation by mesenchymal cells is performed by stem cells that reside in cervical loop of the incisor apex. However, little is known about the mechanisms of stem cell compartment formation. Recently, a mouse incisor was used as a model to show that fibroblast growth factor (FGF) 10 regulates mitogenesis and fate decision of adult stem cells. To further illustrate the role of FGF10 in the formation of the stem cell compartment during tooth organogenesis, we have analyzed incisor development in Fgf10-deficient mice and have examined the effects of neutralizing anti-FGF10 antibody on the developing incisors in organ cultures. The incisor germs of FGF10-null mice proceeded to cap stage normally. However, at a later stage, the cervical loop was not formed. We found that the absence of the cervical loop was due to a divergence in Fgf10 and Fgf3 expression patterns at E16. Furthermore, we estimated the growth of dental epithelium from incisor explants of FGF10-null mice by organ culture. The dental epithelium of FGF10-null mice showed limited growth, although the epithelium of wild-type mice appeared to grow normally. In other experiments, a functional disorder of FGF10, caused by a neutralizing anti-FGF10 antibody, induced apoptosis in the cervical loop of developing mouse incisor cultures. However, recombinant human FGF10 protein rescued the cervical loop from apoptosis. Taken together, these results suggest that FGF10 is a survival factor that maintains the stem cell population in developing incisor germs.

2007 ◽  
Vol 404 (2) ◽  
pp. 169-178 ◽  
Author(s):  
Zoë D. Burke ◽  
Shifaan Thowfeequ ◽  
Macarena Peran ◽  
David Tosh

Stem cells are undifferentiated cells that can self-renew and generate specialized (functional) cell types. The remarkable ability of stem cells to differentiate towards functional cells makes them suitable modalities in cellular therapy (which means treating diseases with the body's own cells). Potential targets for cellular therapy include diabetes and liver failure. However, in order for stem cells to be clinically useful, we must learn to identify them and to regulate their differentiation. We will use the intestine as a classical example of a stem cell compartment, and then examine the evidence for the existence of adult stem cells in two endodermally derived organs: pancreas and liver. We will review the characteristics of the putative stem cells in these tissues and the transcription factors controlling their differentiation towards functional cell types.


1997 ◽  
Vol 45 (6) ◽  
pp. 867-874 ◽  
Author(s):  
Jean-Pierre Molès ◽  
Fiona M. Watt

The basal layer of the epidermis contains two types of proliferating keratinocyte: stem cells, with high proliferative potential, and transit amplifying cells, which are destined to undergo terminal differentiation after a few rounds of division. It has been shown previously that two- to three-fold differences in the average staining intensity of fluorescein-conjugated antibodies to β1 integrin subunits reflect profound differences in the proliferative potential of keratinocytes, with integrin-bright populations being enriched for stem cells. In the search for additional stem cell markers, we have stained sections of normal human epidermis with antibodies to proteins involved in intercellular adhesion and quantitated the fluorescence of individual cell-cell borders. In the basal layer, patches of brightly labeled cells were detected with antibodies to E-cadherin, β-catenin, and γ-catenin, but not with antibodies to P-cadherin, α-catenin, or with pan-desmocollin and pan-desmoglein antibodies. In the body sites examined, palm and foreskin, integrinbright regions were strongly labeled for γ-catenin and weakly labeled for E-cadherin and β-catenin. Our data suggest that there are gradients of both cell-cell and cell-extracellular matrix adhesiveness within the epidermal basal layer and that the levels of E-cadherin and of β-and γ-catenin may provide markers for the stem cell compartment, stem cells expressing relatively higher levels of γ-catenin and lower levels of E-cadherin and β-catenin than other basal keratinocytes.


2014 ◽  
Vol 59 (2) ◽  
pp. 273-280 ◽  
Author(s):  
Mariusz Z. Ratajczak ◽  
Krzysztof Marycz ◽  
Agata Poniewierska-Baran ◽  
Katarzyna Fiedorowicz ◽  
Monika Zbucka-Kretowska ◽  
...  

Blood ◽  
1976 ◽  
Vol 47 (2) ◽  
pp. 315-323 ◽  
Author(s):  
RL DeGowin ◽  
DP Gibson

Abstract To determine if mononuclear cells proliferating in murine hemopoietic spleen colonies were pluripotential in addition to possessing kinetic features of stem cells, we performed sequential studies of mice during their recovery from a split-dose irradiation regimen of 850 roentgens leg shielded-3-hr interval-850 roentgens leg irradiated (850R L.S. 3- L.I.). Injecting tritiated thymidine during stem cell compartment repletion 3 and 4 days after 850R L.S. 3- L.I. resulted in heavily labeled mononuclear cells resembling medium to large leptochromatic lymphocytes in the portion of spleen removed an hour after injection. The splenic remnant obtained from the same mouse 24–48 hr later contained lightly labeled erythroblasts, myeloid cells, and lymphoid cells. Grain counts suggested that erythroblasts and their precursors had undergone about four divisions, myeloid cells and their precursors two to three divisions, and lymphoid cells and their precursors two to three divisions during the 48-hr period. Similar studies in plethoric mice demonstrated the labeling of mononuclear cells on day 4 and their differentiation to myeloid and lymphoid cells by day 6. This finding confirmed that the labeled mononuclear cells were not exclusively erythroblast progenitors. On the basis of these and previous studies of post-irradiation survival and erythropoietic recovery, we conclude that these endogenous monomuclear cells, which resemble medium to large leptochromatic lymphocytes and replicate during stem cell compartment repletion, are pluripotential hemopoietic stem cells.


2020 ◽  
Vol 117 (14) ◽  
pp. 8064-8073 ◽  
Author(s):  
Steven J. Mileto ◽  
Thierry Jardé ◽  
Kevin O. Childress ◽  
Jaime L. Jensen ◽  
Ashleigh P. Rogers ◽  
...  

Gastrointestinal infections often induce epithelial damage that must be repaired for optimal gut function. While intestinal stem cells are critical for this regeneration process [R. C. van der Wath, B. S. Gardiner, A. W. Burgess, D. W. Smith,PLoS One8, e73204 (2013); S. Kozaret al.,Cell Stem Cell13, 626–633 (2013)], how they are impacted by enteric infections remains poorly defined. Here, we investigate infection-mediated damage to the colonic stem cell compartment and how this affects epithelial repair and recovery from infection. Using the pathogenClostridioides difficile,we show that infection disrupts murine intestinal cellular organization and integrity deep into the epithelium, to expose the otherwise protected stem cell compartment, in a TcdB-mediated process. Exposure and susceptibility of colonic stem cells to intoxication compromises their function during infection, which diminishes their ability to repair the injured epithelium, shown by altered stem cell signaling and a reduction in the growth of colonic organoids from stem cells isolated from infected mice. We also show, using both mouse and human colonic organoids, that TcdB from epidemic ribotype 027 strains does not require Frizzled 1/2/7 binding to elicit this dysfunctional stem cell state. This stem cell dysfunction induces a significant delay in recovery and repair of the intestinal epithelium of up to 2 wk post the infection peak. Our results uncover a mechanism by which an enteric pathogen subverts repair processes by targeting stem cells during infection and preventing epithelial regeneration, which prolongs epithelial barrier impairment and creates an environment in which disease recurrence is likely.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1551-1551
Author(s):  
Janina Ratajczak ◽  
Wu Wan ◽  
Rui Liu ◽  
Dong-Myung Shin ◽  
Magdalena Kucia ◽  
...  

Abstract Abstract 1551 Insulin-like growth factor-1 (Igf-1) or somatomedin is an important factor affecting proliferation of several types of cells, but its role in hematopoiesis remains controversial. Secretion of Igf-1 in the liver is stimulated directly by the growth hormone (GH)–GH receptor (GH-R) axis and indirectly by a high calorie diet. We have previously reported that Igf-1 does not directly stimulate proliferation of hematopoietic progenitors (J Clin Invest. 1994;94:320). However, our recent data indicate that Igf-1 stimulates proliferation of so-called very small embryonic-like stem cells (VSELs), that as we demonstrated, are the most developmentally primitive stem cells in adult bone marrow (BM) (Leukemia 2006;20:857) and may give rise to long-term repopulating hematopoietic stem cells (LT-HSCs) (Leukemia 2010; in press doi:10.1038/leu.2010.121). We envision that VSELs play a role in rejuvenation of the pool of tissue-committed stem cells in some tissues (e.g., HSCs and MSCs in BM) and we observed that the number of these cells in murine BM decreases with age. We also observed that erasure of the somatic imprint on some paternally imprinted genes (e.g., Igf2-H19 and RasGRF1) results in attenuation of insulin/insulin-like factors (e.g., Ins/Igf-1 signaling), keeps VSELs quiescent in BM, and protects them from uncontrolled proliferation. In the current work, to shed more light on the role of Igf-1 on hematopoiesis and stem cell compartment, we analyzed BM isolated from murine Laron dwarfs, which due to a genetic mutation in the GH-R, maintain very low levels of Igf-1 in peripheral blood (PB) and interestingly are long-living animals (Nature 2010;464:504). Analysis of PB cell counts, however, did not reveal any differences in the number of erythrocytes, platelets, and leucocytes between Laron dwarf mice and wild type controls. In striking contrast, however, we observed that Laron dwarf mice have in BM i) a ∼4–5-fold increase in the number of Sca-1+c-kit+lineage- (SKL) cells and ii) a >4-fold higher number of clonogenic CFU-Mix, CFU-GM, BFU-E, and CFU-Meg cells. Interestingly, Laron dwarfs also maintained ∼3-fold higher number of VSELs in BM tissue. Since the Igf-1 level is regulated by calorie uptake, these data shed new light on caloric restriction, senescence, and the hematopoietic stem cell compartment. Accordingly, we propose a new paradigm in which chronic Igf-1 deficiency somehow protects VSELs from age-related elimination from BM. This mimics a situation seen in chronic caloric restriction where the Igf-1 level is low and this results in longevity. Since the long-living Laron dwarf mice that maintain low levels of Igf-1 have higher numbers of VSELs and HSCs in BM, we postulate that chronically elevated levels of Igf-1, resulting e.g., from high calorie uptake, may lead to premature depletion of the stem cell pool, including VSELs and HSCs, and thus be responsible for premature aging. This hypothesis is currently being tested in animals that overexpress Igf-1, and interestingly, in contrast to IGF-1–deficient Laron dwarf mice, appear to have much shorter lifespans. Further studies are needed that will link the effect of chronic high Igf-1 signaling with the development of hematological malignancies. Of note, murine Laron dwarfs are significantly protected from developing cancer and human Laron dwarfs with chronic low Igf-1 level do not develop malignancies at all. Disclosures: No relevant conflicts of interest to declare.


2016 ◽  
Vol 202 (5-6) ◽  
pp. 269-280 ◽  
Author(s):  
Daniel Martinez Saez ◽  
Robson Tetsuo Sasaki ◽  
Adriana da Costa Neves ◽  
Marcelo Cavenaghi Pereira da Silva

Adult stem cells research has been considered the most advanced sort of medical-scientific research, particularly stem cells from human exfoliated deciduous teeth (SHED), which represent an immature stem cell population. The purpose of this review is to describe the current knowledge concerning SHED from full-text scientific publications from 2003 to 2015, available in English language and based on the keyword and/or abbreviations ‘stem cells from human exfoliated deciduous teeth (SHED)', and individually presented as to the properties of SHED, immunomodulatory properties of SHED and stem cell banking. In summary, these cell populations are easily accessible by noninvasive procedures and can be isolated, cultured and expanded in vitro, successfully differentiated in vitro and in vivo into odontoblasts, osteoblasts, chondrocytes, adipocytes and neural cells, and present low immune reactions or rejection following SHED transplantation. Furthermore, SHED are able to remain undifferentiated and stable after long-term cryopreservation. In conclusion, the high proliferative capacity, easy access, multilineage differentiation capacity, noninvasiveness and few ethical concerns make stem cells from human exfoliated deciduous teeth the most valuable source of stem cells for tissue engineering and cell-based regenerative medicine therapies.


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