Dependence of Kidney Morphogenesis on the Expression of Nerve Growth Factor Receptor

Sariola, Hannu; Saarma, Märt; Sainio, Kirsi; Arumäe, Urmas; Palgi, Jaan; Vaahtokari, Anne; Thesleff, Irma; Караванов, А А

doi:10.1126/science.1658930

Cited by 175 publications

(73 citation statements)

References 38 publications

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“…These results led us to conclude that cellular characteristics of p75 NGFR -expressing cells are similar to that of reserve cells noted in various epithelial basal layer. A number of previous studies agree that bcl-2 acts against cell proliferation, cell death, apoptosis and di erentiation in many normal cell types (Buck et al, 1987;Sariola et al, 1991;Polakowska et al, 1994;Reed, 1994 for a review; Harada et al, 1998). In this context, the p75 NGFR -expressing basal cell subset is distinct from a specialized cell type committed toward terminal di erentiation.…”

Section: Discussionmentioning

confidence: 93%

Telomerase activity in a specific cell subset co-expressing integrinβ1/EGFR but not p75NGFR/bcl2/integrin β4 in normal human epithelial cells

Kikuchi

Ahmed

et al. 1998

Oncogene

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Telomerase activity is correlated with the immortality of various cultured cells and cancer cells. The activity, however, is also demonstrated in various normal regenerating cells which normally have a ®nite life span in vivo and in vitro, though its biological implication remains unclear. Using cultured normal human epithelial cells, we show that telomerase activity is associated with epithelial cell subsets which actively proliferate in vitro. Unlike in most cancer cell lines, telomerase activity was evidently up-regulated when the cells entered into S phase in primary human epithelial cells. To characterize the cells which have telomerase activity, the primary human epithelial cell population of uterine cervix was dissociated into several distinctive cellular subsets by means of immunocytochemical cell fractionation. Telomerase activity was found to be closely associated with the subset which expressed predominantly integrin b1 and epidermal growth factor receptor. We further identi®ed the telomerase-negative subpopulation which contained a small subset that strongly coexpresses p75 NGFR low a nity nerve growth factor receptor, integrin b4 and bcl-2 protein. The location of the p75 NGFR -expressing cells contrasts to that of the Ki-67 positive cells in vivo and is distinctive of telomerase positive cycling cells, indicating that these cells remain at the G0 phase. The present study supports the notion that telomerase activity is linked to cell cycle regulation, implying that telomerase is activated upon cell proliferation in regenerating normal human epithelial cells.

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Section: Discussionmentioning

confidence: 93%

Telomerase activity in a specific cell subset co-expressing integrinβ1/EGFR but not p75NGFR/bcl2/integrin β4 in normal human epithelial cells

Kikuchi

Ahmed

et al. 1998

Oncogene

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“…Altogether, our data suggest that the selection with anti-L-NGFR MoAb allows us to obtain a more homogeneous and primitive population: the almost total co-expression of CD34, the expression of the stem markers CD117 and CD105, and the higher proliferative, clonogenic, and differentiative potential, in particular at early passages, seem to support this observation. The role of L-NGFR in MSCs is still unclear, although its expression has been described in BM and in other tissues [ 34 , 57 ] and it has been shown to be involved in several functions including morphogenesis [58][59][60][61], growth factor presentation [ 62 ], and apoptosis in response to NGF stimulation [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-L-NGFR and -CD34 Monoclonal Antibodies Identify Multipotent Mesenchymal Stem Cells in Human Adipose Tissue

Quirici

Scavullo

Girolamo

et al. 2010

Stem Cells and Development

103

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Stem cells hold great promise in tissue engineering for repairing tissues damaged by disease or injury. Mesenchymal stem cells (MSCs) are multipotent cells able to proliferate and differentiate into multiple mesodermal tissues such as bone, cartilage, muscle, tendon, and fat. We have previously reported that the low-affi nity nerve growth factor receptor (L-NGFR or CD271) defi nes a subset of cells with high proliferative, clonogenic, and multipotential differentiation ability in adult bone marrow (BM). It has been recently shown that adipose tissue is an alternative source of adult multipotent stem cells and human adipose-derived stem cells, selected by plastic adherence (PA hASCs), have been extensively characterized for their functional potentials in vitro. In this study, immunoselected L-NGFR + and CD34 + subpopulations have been analyzed and compared with the PA hASCs. Phenotypic profi le of freshly purifi ed subpopulations showed an enrichment in the expression of some stem cell markers; indeed, a great percentage of L-NGFR + cells co-expressed CD34 and CD117 antigens, whereas the endothelial-committed progenitor markers KDR and P1H12 were mainly expressed on CD34 + cells. Differently from PA hASCs, the immunoseparated fractions showed high increments in cell proliferation, and the fi broblast colony-forming activity (CFU-F) was maintained throughout the time of culture. Furthermore, the immunoselected populations showed a greater differentiative potential toward adipocytes, osteoblasts, and chondrocytelike cells, compared to PA hASCs. Our data suggest that both CD34+ and L-NGFR + hASCs can be considered alternative candidates for tissue engineering and regenerative medicine applications. IntroductionI n the recent years, the emerging fi eld of cell-based therapies for repair and regeneration of damaged tissues has been focusing on the identifi cation of the ideal source of stem cells, which combines the ability of multipotential differentiation and the accessibility in large amounts under a minimally invasive procedure, not complicated by immunological rejection concerns and ethical controversies.Adult mesenchymal stem cells (MSCs) are a population of multipotent cells able to proliferate and differentiate into multiple mesodermal tissues. MSCs have been initially identifi ed in bone marrow (BM) [ 1 ], but have been subsequently isolated from many other tissues [ 2-10 ]. Among them, human MSCs derived from adipose tissue (hASCs) show stem cell key features such as the ability to form fi broblast-like colonies (CFU-F), the expression of several common cell surface antigens, the capacity of extensive proliferation, and the potential to differentiate in vitro and in vivo into multiple lineages of mesodermal origin, and also to transdifferentiate into neurogenic and hepatic lineages [ 4 , 11-21 ]. Similarly to BM-derived MSCs (BM MSCs), hASCs are able to suppress immunoreactivity, suggesting a possible overcoming of histocompatibility limitations in allogeneic transplantation [ 22 , 23 ]; furthermore, they ar...

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“…Recently, physiological functions of this receptor type were described in transgenic mice. including involvement in morphogenesis of kidney [29] and an essential role in the development and function of sensory neurons which innervate cutaneous tissues [30]. It will be interesting to determine whether any of these functions can be connected to rapid CAMP responses.…”

Section: In Further Experimentsmentioning

confidence: 99%

Neurotrophin induced cAMP and IP₃ responses in PC12 cells

et al. 1993

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NGF and BDNF elevate cAMP and IP3 levels in membranes of PC12 cells within a subsecond time period. The cAM P formation induced by NGF and BDNF pretreatment for 2 s was reduced by GDP‐β‐S and PTX, but not the trkNGFR inhibitor K 252a. NGF, but not BDNF, induced IP3 formation. IP3 formation was reduced by K 252a, but not by GDP‐β‐S and PTX. Using p75NGFR expressing, but trkNGFR‐deficient PCNA cell membranes, NGF and BDNF induced cAMP formation, but not IP3 formation. We suggest that NGF and BDNF induced cAMP formation is mediated via a p75NGFR/G‐protein mediated mechanism, and IP3 formation via a K 252a sensitive pathway.

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Dependence of Kidney Morphogenesis on the Expression of Nerve Growth Factor Receptor

Cited by 175 publications

References 38 publications

Telomerase activity in a specific cell subset co-expressing integrinβ1/EGFR but not p75NGFR/bcl2/integrin β4 in normal human epithelial cells

Telomerase activity in a specific cell subset co-expressing integrinβ1/EGFR but not p75NGFR/bcl2/integrin β4 in normal human epithelial cells

Anti-L-NGFR and -CD34 Monoclonal Antibodies Identify Multipotent Mesenchymal Stem Cells in Human Adipose Tissue

Neurotrophin induced cAMP and IP₃ responses in PC12 cells

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Dependence of Kidney Morphogenesis on the Expression of Nerve Growth Factor Receptor

Cited by 175 publications

References 38 publications

Telomerase activity in a specific cell subset co-expressing integrinβ1/EGFR but not p75NGFR/bcl2/integrin β4 in normal human epithelial cells

Telomerase activity in a specific cell subset co-expressing integrinβ1/EGFR but not p75NGFR/bcl2/integrin β4 in normal human epithelial cells

Anti-L-NGFR and -CD34 Monoclonal Antibodies Identify Multipotent Mesenchymal Stem Cells in Human Adipose Tissue

Neurotrophin induced cAMP and IP3 responses in PC12 cells

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Neurotrophin induced cAMP and IP₃ responses in PC12 cells