Numb Expression Contributes to the Maintenance of an Undifferentiated State in Human Epidermis
The epidermis is a stratified epithelium with a stem cell subpopulation in the basal layer that constantly replicates and periodically detaches from the base, undergoing a differentiation process that involves various developmental signals and regulatory pathways. During the last 10 years, a number...
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doaj-b771dde163c64f2c8030fc12e31280f42020-11-25T03:03:21ZengSAGE PublishingCell Transplantation0963-68971555-38922016-02-012510.3727/096368915X688245Numb Expression Contributes to the Maintenance of an Undifferentiated State in Human EpidermisGioacchin Iannolo0Maria Rita Sciuto1Simona Buccheri2Cristina Colarossi3Ruggero De Maria4Lorenzo Memeo5Pier Giulio Conaldi6 Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo, Italy Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo, Italy Department of Experimental Oncology, Mediterranean Institute of Oncology (IOM), Viagrande, Catania, Italy National Cancer Institute ‘Regina Elena’, Rome, Italy Department of Experimental Oncology, Mediterranean Institute of Oncology (IOM), Viagrande, Catania, Italy Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo, ItalyThe epidermis is a stratified epithelium with a stem cell subpopulation in the basal layer that constantly replicates and periodically detaches from the base, undergoing a differentiation process that involves various developmental signals and regulatory pathways. During the last 10 years, a number of studies tried to elucidate the intricate scenario that maintains the epithelial shield during the entire life span. In our study, we investigated the role of Numb in the skin compartment and, in particular, its involvement in stem cell maintenance. Numb expression in the skin compartment was assessed by immunofluorescence and immunohistochemistry analysis. We evaluated Numb expression in primary epithelial cells at various differentiative stages. Moreover, we overexpressed Numb in the isolated population enriched for undifferentiated progenitors to establish its involvement in in vitro differentiation. We demonstrated that Numb in high-proliferating epithelial undifferentiated progenitors contributes to the maintenance of an undifferentiated state. This regulation involves the E3 ligases Itch binding. Moreover, the analysis of a cohort of cutaneous carcinomas showed that Numb is highly expressed in squamous cell carcinoma (SCC), where we observed a direct correlation between the expression of Numb and Ki-67. Our data indicate for the first time that Numb is involved in the maintenance of the undifferentiated proliferating stem cell pool in the epithelial basal layer and its expression could become a new marker in skin cancer.https://doi.org/10.3727/096368915X688245 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gioacchin Iannolo Maria Rita Sciuto Simona Buccheri Cristina Colarossi Ruggero De Maria Lorenzo Memeo Pier Giulio Conaldi |
spellingShingle |
Gioacchin Iannolo Maria Rita Sciuto Simona Buccheri Cristina Colarossi Ruggero De Maria Lorenzo Memeo Pier Giulio Conaldi Numb Expression Contributes to the Maintenance of an Undifferentiated State in Human Epidermis Cell Transplantation |
author_facet |
Gioacchin Iannolo Maria Rita Sciuto Simona Buccheri Cristina Colarossi Ruggero De Maria Lorenzo Memeo Pier Giulio Conaldi |
author_sort |
Gioacchin Iannolo |
title |
Numb Expression Contributes to the Maintenance of an Undifferentiated State in Human Epidermis |
title_short |
Numb Expression Contributes to the Maintenance of an Undifferentiated State in Human Epidermis |
title_full |
Numb Expression Contributes to the Maintenance of an Undifferentiated State in Human Epidermis |
title_fullStr |
Numb Expression Contributes to the Maintenance of an Undifferentiated State in Human Epidermis |
title_full_unstemmed |
Numb Expression Contributes to the Maintenance of an Undifferentiated State in Human Epidermis |
title_sort |
numb expression contributes to the maintenance of an undifferentiated state in human epidermis |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2016-02-01 |
description |
The epidermis is a stratified epithelium with a stem cell subpopulation in the basal layer that constantly replicates and periodically detaches from the base, undergoing a differentiation process that involves various developmental signals and regulatory pathways. During the last 10 years, a number of studies tried to elucidate the intricate scenario that maintains the epithelial shield during the entire life span. In our study, we investigated the role of Numb in the skin compartment and, in particular, its involvement in stem cell maintenance. Numb expression in the skin compartment was assessed by immunofluorescence and immunohistochemistry analysis. We evaluated Numb expression in primary epithelial cells at various differentiative stages. Moreover, we overexpressed Numb in the isolated population enriched for undifferentiated progenitors to establish its involvement in in vitro differentiation. We demonstrated that Numb in high-proliferating epithelial undifferentiated progenitors contributes to the maintenance of an undifferentiated state. This regulation involves the E3 ligases Itch binding. Moreover, the analysis of a cohort of cutaneous carcinomas showed that Numb is highly expressed in squamous cell carcinoma (SCC), where we observed a direct correlation between the expression of Numb and Ki-67. Our data indicate for the first time that Numb is involved in the maintenance of the undifferentiated proliferating stem cell pool in the epithelial basal layer and its expression could become a new marker in skin cancer. |
url |
https://doi.org/10.3727/096368915X688245 |
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