scholarly journals ΔN-Tp63 Mediates Wnt/β-Catenin-Induced Inhibition of Differentiation in Basal Stem Cells of Mucociliary Epithelia

Cell Reports ◽  
2019 ◽  
Vol 28 (13) ◽  
pp. 3338-3352.e6 ◽  
Author(s):  
Maximilian Haas ◽  
José Luis Gómez Vázquez ◽  
Dingyuan Iris Sun ◽  
Hong Thi Tran ◽  
Magdalena Brislinger ◽  
...  
Keyword(s):  
Stem Cells ◽  
Inhibition Of Differentiation ◽  
Mucociliary Epithelia

scholarly journals ΔN-Tp63 mediates Wnt/β-catenin-induced inhibition of differentiation in basal stem cells of mucociliary epithelia

2019 ◽  
Author(s):  
Maximilian Haas ◽  
José Luis Gómez Vázquez ◽  
Dingyuan Iris Sun ◽  
Hong Thi Tran ◽  
Magdalena Brislinger ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wnt Signaling ◽  
Basal Cells ◽  
Cell Hyperplasia ◽  
Chronic Lung Diseases ◽  
Evolutionarily Conserved ◽  
Inhibition Of Differentiation ◽  
Mucociliary Epithelia

SummaryMucociliary epithelia provide a first line of defense against pathogens in the airways and the epidermis of vertebrate larvae. Impaired regeneration and remodeling of mucociliary epithelia are associated with dysregulated Wnt/β-catenin signaling in chronic airway diseases, but underlying mechanisms remain elusive and studies of Wnt signaling in mucociliary cells yield seemingly contradicting results. Employing the Xenopus mucociliary epidermis, the mouse airway, and human airway basal stem cell cultures, we characterize the evolutionarily conserved roles of Wnt/β-catenin signaling in mucociliary cells in vertebrates. Wnt signaling is required in multiciliated cells for cilia formation during differentiation stages, but in Basal cells, Wnt signaling prevents specification and differentiation of epithelial cell types by activating ΔN-TP63 expression. We demonstrate that ΔN-TP63 is a master transcription factor in Basal cells, which is necessary and sufficient to mediate the Wnt-induced inhibition of differentiation and is required to retain basal stem cells during development. Chronic stimulation of Wnt signaling leads to mucociliary remodeling and Basal cell hyperplasia, but this is reversible in vivo and in vitro, suggesting Wnt inhibition as an option in the treatment of chronic lung diseases. Our work sheds light into the evolutionarily conserved regulation of stem cells and differentiation, resolves Wnt functions in mucociliary epithelia, and provides crucial insights into mucociliary development, regeneration and disease mechanisms.

scholarly journals Signaling Control of Mucociliary Epithelia: Stem Cells, Cell Fates, and the Plasticity of Cell Identity in Development and Disease

2021 ◽  
pp. 1-18
Author(s):  
Peter Walentek
Keyword(s):  
Stem Cells ◽  
Mucociliary Clearance ◽  
Cell Types ◽  
Secretory Cells ◽  
Chronic Obstructive ◽  
Cell Identity ◽  
Obstructive Pulmonary Disease ◽  
Congenital Diseases ◽  
Inhaled Particles ◽  
Mucociliary Epithelia

Mucociliary epithelia are composed of multiciliated, secretory, and stem cells and line various organs in vertebrates such as the respiratory tract. By means of mucociliary clearance, those epithelia provide a first line of defense against inhaled particles and pathogens. Mucociliary clearance relies on the correct composition of cell types, that is, the proper balance of ciliated and secretory cells. A failure to generate and to maintain correct cell type composition and function results in impaired clearance and high risk to infections, such as in congenital diseases (e.g., ciliopathies) as well as in acquired diseases, including asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). While it remains incompletely resolved how precisely cell types are specified and maintained in development and disease, many studies have revealed important mechanisms regarding the signaling control in mucociliary cell types in various species. Those studies not only provided insights into the signaling contribution to organ development and regeneration but also highlighted the remarkable plasticity of cell identity encountered in mucociliary maintenance, including frequent trans-differentiation events during homeostasis and specifically in disease. This review will summarize major findings and provide perspectives regarding the future of mucociliary research and the treatment of chronic airway diseases associated with tissue remodeling.

scholarly journals Apoptosis: Reprogramming and the Fate of Mature Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Hoi-Hung Cheung ◽  
Xiaozhuo Liu ◽  
Owen M. Rennert
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Multiple Roles ◽  
Proliferative Potential ◽  
Self Renewal ◽  
Differentiated Cells ◽  
Inhibition Of Differentiation

Apoptosis is essential for embryogenesis, organ metamorphosis, and tissue homeostasis. In embryonic stem cells, self-renewal is balanced with proliferative potential, inhibition of differentiation, and prevention of senescence and apoptosis. Growing evidence supports the role of apoptosis in self-renewal, differentiation of pluripotent stem cells, and dedifferentiation (reprogramming) of somatic cells. In this paper we discuss the multiple roles of apoptosis in embryonic stem cells (ESCs) and reprogramming of differentiated cells to pluripotency. The role of caspases and p53 as key effectors in controlling the generation of iPSC is emphasized. Remarkably, the complication of apoptosis arising during reprogramming may provide insights into technical improvements for derivation of iPSC from senescent cells as a tool for modeling aging-related diseases.

Proliferation and multi-differentiation potentials of human mesenchymal stem cells on thermoresponsive PDMS surfaces grafted with PNIPAAm

2010 ◽  
Vol 30 (6) ◽  
pp. 455-455 ◽  
Author(s):  
Dongyan Shi ◽  
Dan Ma ◽  
Feiqing Dong ◽  
Chen Zong ◽  
Liyue Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells

Repair of deep skin burn defects with cultured epidermal stem cells and acellular amniotic membranes

2010 ◽  
Vol 34 (8) ◽  
pp. S39-S39
Author(s):  
Dewu Liu ◽  
Honglan Xiong ◽  
Yuangui Mao ◽  
Peixin Huang ◽  
Jianping Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epidermal Stem Cells ◽  
Skin Burn ◽  
Amniotic Membranes

Directed differentiation of mouse-induced pluripotent stem cells generates dopaminergic nerve

2010 ◽  
Vol 34 (8) ◽  
pp. S36-S36
Author(s):  
Ping Duan ◽  
Xuelin Ren ◽  
Wenhai Yan ◽  
Xuefei Han ◽  
Xu Yan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Directed Differentiation ◽  
Induced Pluripotent

Preliminary research of the aldosterone synthesized by bone morrow stem cells of adult male ratsin vitro

2010 ◽  
Vol 34 (8) ◽  
pp. S43-S43
Author(s):  
Wei‑ying Zou ◽  
Bei Yang ◽  
Xiuli Ni ◽  
Da‑lei Zhang ◽  
Lei Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adult Male ◽  
Preliminary Research ◽  
Bone Morrow
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