scholarly journals Basal cells in the epidermis and epidermal differentiation

2021 ◽  
Author(s):  
Raghvendra Singh
Keyword(s):  
Stem Cells ◽  
Clonal Growth ◽  
Growth Analysis ◽  
Basal Layer ◽  
Lineage Tracing ◽  
Epidermal Differentiation ◽  
Basal Cells ◽  
Epidermal Stem Cells ◽  
Cellular Composition ◽  
Developmental Patterning

Abstract A definite identification of epidermal stem cells is not known and the mechanism of epidermal differentiation is not fully understood. Toward both of these quests, considerable information is available from the research on lineage tracing and clonal growth analysis in the basal layer of the epidermis, on the hair follicle and interfollicular epidermal stem cells, and on Wnt signaling along with its role in developmental patterning and cell differentiation. In this paper, literature on the aforementioned research has been collated and analyzed. In addition, models of basal layer cellular composition and epidermal differentiation have been presented.

scholarly journals Murine interfollicular epidermal differentiation is gradualistic with GRHL3 controlling progression from stem to transition cell states

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ziguang Lin ◽  
Suoqin Jin ◽  
Jefferson Chen ◽  
Zhuorui Li ◽  
Zhongqi Lin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Skin Diseases ◽  
Basal Layer ◽  
Terminal Differentiation ◽  
Skin Surface ◽  
Single Step ◽  
Epidermal Differentiation ◽  
Inflammatory Skin Diseases ◽  
Cell State

Abstract The interfollicular epidermis (IFE) forms a water-tight barrier that is often disrupted in inflammatory skin diseases. During homeostasis, the IFE is replenished by stem cells in the basal layer that differentiate as they migrate toward the skin surface. Conventionally, IFE differentiation is thought to be stepwise as reflected in sharp boundaries between its basal, spinous, granular and cornified layers. The transcription factor GRHL3 regulates IFE differentiation by transcriptionally activating terminal differentiation genes. Here we use single cell RNA-seq to show that murine IFE differentiation is best described as a single step gradualistic process with a large number of transition cells between the basal and spinous layer. RNA-velocity analysis identifies a commitment point that separates the plastic basal and transition cell state from unidirectionally differentiating cells. We also show that in addition to promoting IFE terminal differentiation, GRHL3 is essential for suppressing epidermal stem cell expansion and the emergence of an abnormal stem cell state by suppressing Wnt signaling in stem cells.

scholarly journals Identification of a basal stem cell subpopulation in the prostate via functional, lineage tracing and single-cell RNA-seq analyses

2019 ◽  
Author(s):  
Xue Wang ◽  
Haibo Xu ◽  
Chaping Cheng ◽  
Zhongzhong Ji ◽  
Huifang Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Epithelial Cells ◽  
Single Cell ◽  
Basal Cell ◽  
Lineage Tracing ◽  
Cell Subpopulation ◽  
Basal Cells ◽  
Mesenchymal Transition ◽  
Genetic Ablation

AbstractThe basal cell compartment in many epithelial tissues such as the prostate, bladder, and mammary gland are generally believed to serve as an important pool of stem cells. However, basal cells are heterogenous and the stem cell subpopulation within basal cells is not well elucidated. Here we uncover that the core epithelial-to-mesenchymal transition (EMT) inducer Zeb is exclusively expressed in a prostate basal cell subpopulation based on both immunocytochemical and cell lineage tracing analysis. The Zeb1+prostate epithelial cells are multipotent prostate basal stem cells (PBSCs) that can self-renew and generate functional prostatic glandular structures with all three epithelial cell types at the single-cell level. Genetic ablation studies reveal an indispensable role for Zeb1 in prostate basal cell development. Utilizing unbiased single cell transcriptomic analysis of over 9000 mouse prostate basal cells, we find that Zeb1+basal cell subset shares gene expression signatures with both epithelial and mesenchymal cells and stands out uniquely among all the basal cell clusters. Moreover, Zeb1+epithelial cells can be detected in mouse and clinical samples of prostate tumors. Identification of the PBSC and its transcriptome profile is crucial to advance our understanding of prostate development and tumorigenesis.

Label-retaining cells of the bladder: candidate urothelial stem cells

2008 ◽  
Vol 294 (6) ◽  
pp. F1415-F1421 ◽  
Author(s):  
Eric A. Kurzrock ◽  
Deborah K. Lieu ◽  
Lea A. deGraffenried ◽  
Camie W. Chan ◽  
Roslyn R. Isseroff
Keyword(s):  
Stem Cells ◽  
Basal Layer ◽  
Basal Cells ◽  
Bladder Epithelium ◽  
Chase Period ◽  
Brdu Label ◽  
Dividing Cells ◽  
Β4 Integrin ◽  
Cytokeratin 14

Adult tissue stem cells replicate infrequently, retaining DNA nucleotide label (BrdU) for much longer periods than mature, dividing cells in which the label is diluted during a chase period. Those “label-retaining cells” (LRCs) have been identified as the tissue stem cells in skin, cornea, intestine, and prostate. However, in the urinary tract uroepithelial stem cells have not yet been identified. In this study, BrdU administration identified urothelial LRCs in the rat bladder with 9% of the epithelial basal cells retaining BrdU label 1 yr after its administration. Markers for stem cells in other tissues, Bcl, p63, cytokeratin 14, and β1 integrin, were immunolocalized in the basal bladder epithelium in or near urothelial LRCs, but not uniquely limited to these cells. Flow cytometry demonstrated that urothelial LRCs were small, had low granularity, and were uniquely β4 integrin bright. Urothelium from long-term labeled bladders was cultured and LRCs were found to be significantly more clonogenic and proliferative, characteristics of stem cells, than unlabeled urothelial cells. Thus, this work demonstrates that LRCs in the bladder localize to the basal layer, are small, low granularity, uniquely β4 integrin rich, slowly cycling and demonstrate superior clonogenic and proliferative ability compared with unlabeled epithelial cells. We propose that LRCs represent putative urothelial stem cells.

scholarly journals Acute inflammation regulates neuroregeneration through the NF-κB pathway in olfactory epithelium

2017 ◽  
Vol 114 (30) ◽  
pp. 8089-8094 ◽  
Author(s):  
Mengfei Chen ◽  
Randall R. Reed ◽  
Andrew P. Lane
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Olfactory Epithelium ◽  
Acute Inflammation ◽  
Basal Layer ◽  
Basal Cells ◽  
Genetic Ablation ◽  
Molecular Events ◽  
Tnf Α ◽  
Horizontal Basal Cells

Adult neural stem cells/progenitor cells residing in the basal layer of the olfactory epithelium are capable of reconstituting the neuroepithelium even after severe damage. The molecular events underlying this regenerative capacity remain elusive. Here we show that the repair of neuroepithelium after lesioning is accompanied by an acute, but self-limited, inflammatory process. Attenuation of inflammatory cell recruitment and cytokine production by dexamethasone impairs proliferation of progenitor horizontal basal cells (HBCs) and subsequent neuronal differentiation. Using TNF-α receptor-deficient mice, we identify TNF-α signaling as an important contributor to this inflammatory and reparative process, mainly through TNF-α receptor 1. HBC-selective genetic ablation of RelA (p65), the transcriptional activator of the NF-κB pathway, retards inflammation and impedes proliferation at the early stages of regeneration and suggests HBCs directly participate in cross-talk between immune response and neurogenesis. Loss of RelA in the regenerating neuroepithelium perturbs the homeostasis between proliferation and apoptosis while enhancing JNK signaling. Together, our results support a model in which acute inflammation after injury initiates important regenerative signals in part through NF-κB–mediated signaling that activates neural stem cells to reconstitute the olfactory epithelium.

scholarly journals Dorso-ventral heterogeneity in tracheal basal stem cells

Biology Open ◽  
2021 ◽  
Author(s):  
Tomomi Tadokoro ◽  
Keisuke Tanaka ◽  
Shun Osakabe ◽  
Mimoko Kato ◽  
Hisato Kobayashi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Gene Ontology ◽  
Smooth Muscle ◽  
Three Dimensional ◽  
Lineage Tracing ◽  
Basal Cells ◽  
Gene Ontology Analysis ◽  
Organoid Culture

The tracheal basal cells (BCs) function as stem cells to maintain the epithelium in steady state and repair it after injury. The airway is surrounded by cartilage ventrolaterally and smooth muscle dorsally. Lineage tracing using Krt5-CreER shows dorsal BCs produce more, larger, clones than ventral BCs. Large clones were found between cartilage and smooth muscle where subpopulation of dorsal BCs exists. Three-dimensional organoid culture of BCs demonstrated that dorsal BCs show higher colony forming efficacy to ventral BCs. Gene ontology analysis revealed that genes expressed in dorsal BCs are enriched in wound healing while ventral BCs are enriched in response to external stimulus and immune response. Significantly, ventral BCs express Myostatin, which inhibits the growth of smooth muscle cells, and HGF, which facilitates cartilage repair. The results support the hypothesis that BCs from the dorso-ventral airways have intrinsic molecular and behavioural differences relevant to their in vivo function.

Critical role of p63 in the development of a normal esophageal and tracheobronchial epithelium

2004 ◽  
Vol 287 (1) ◽  
pp. C171-C181 ◽  
Author(s):  
Yaron Daniely ◽  
Grace Liao ◽  
Darlene Dixon ◽  
R. Ilona Linnoila ◽  
Adriana Lori ◽  
...  
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Squamous Metaplasia ◽  
Critical Role ◽  
Basal Layer ◽  
Cell Types ◽  
Basal Cells ◽  
Ciliated Cells ◽  
Differentiated Cells ◽  
Unique Cell

The trachea and esophagus originate from the foregut endoderm during early embryonic development. Their epithelia undergo a series of changes involving the differentiation of stem cells into unique cell types and ultimately forming the mature epithelia. In this study, we monitored the expression of p63 in the esophagus and the trachea during development and examined in detail morphogenesis in p63−/− mice. At embryonic day 15.5 (E15.5), the esophageal and tracheobronchial epithelia contain two to three layers of cells; however, only the progenitor cells express p63. These progenitor cells differentiate first into ciliated cells (p63−/β-tubulin IV+) and after birth into mature basal cells (p63+/K14+/K5+/BS-I-B4+). In the adult pseudostratified, columnar tracheal epithelium, K14+/K5+/BS-I-B4+ basal cells stain most intensely for p63, whereas ciliated and mucosecretory cells are negative. In stratified squamous esophageal epithelium and during squamous metaplasia in the trachea, cells in the basal layer stain strongest for p63, whereas p63 staining declines progressively in transient amplifying and squamous differentiated cells. Generally, p63 expression is restricted to human squamous cell carcinomas, and adenocarcinomas and Barrett's metaplasia do not stain for p63. Examination of morphogenesis in newborn p63−/− mice showed an abnormal persistence of ciliated cells in the esophagus. Significantly, in both tissues, lack of p63 expression results in the development of a highly ordered, columnar ciliated epithelium deficient in basal cells. These observations indicate that p63 plays a critical role in the development of normal esophageal and tracheobronchial epithelia and appears to control the commitment of early stem cells into basal cell progeny and the maintenance of basal cells.

scholarly journals Chronic inflammation of middle ear cholesteatoma promotes its recurrence via a paracrine mechanism

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Matthias Schürmann ◽  
Felix Oppel ◽  
Senyao Shao ◽  
Verena Volland-Thurn ◽  
Christian Kaltschmidt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Middle Ear ◽  
Culture Conditions ◽  
Epidermal Differentiation ◽  
Epidermal Stem Cells ◽  
Middle Ear Cholesteatoma ◽  
Surgical Extraction ◽  
Standard Culture ◽  
Lps Treatment ◽  
Tlr4 Antagonist

Abstract Background Cholesteatoma disease is an expanding lesion in the middle ear. Hearing loss and facial paralysis alongside with other intracranial complications are found. No pharmaceutical treatment is available today and recurrence after surgical extraction occurs. We investigated possible TLR4-based mechanisms promoting recurrence and explore possible treatments strategies. Methods We isolated fibroblasts and epidermal stem cells from cholesteatoma tissue and healthy auditory canal skin. Subsequently, their expression under standard culture conditions and after stimulation with LPS was investigated by RT-qPCR. Cell metabolism and proliferation were analysed upon LPS treatment, with and without TLR4 antagonist. An indirect co-culture of fibroblasts and epidermal stem cells isolated from cholesteatoma tissue was utilized to monitor epidermal differentiation upon LPS treatment by RT-qPCR and immunocytochemistry. Results Under standard culture conditions, we detected a tissue-independent higher expression of IL-1β and IL-8 in stem cells, an upregulation of KGF and IGF-2 in both cell types derived from cholesteatoma and higher expression of TLR4 in stem cells derived from cholesteatoma tissue. Upon LPS challenge, we could detect a significantly higher expression of IL-1α, IL-1β, IL-6 and IL-8 in stem cells and of TNF-a, GM-CSF and CXCL-5 in stem cells and fibroblasts derived from cholesteatoma. The expression of the growth factors KGF, EGF, EREG, IGF-2 and HGF was significantly higher in fibroblasts, particularly when derived from cholesteatoma. Upon treatment with LPS the metabolism was elevated in stem cells and fibroblasts, proliferation was only enhanced in fibroblasts derived from cholesteatoma. This could be reversed by the treatment with a TLR4 antagonist. The cholesteatoma fibroblasts could be triggered by LPS to promote the epidermal differentiation of the stem cells, while no LPS treatment or LPS treatment without the presence of fibroblasts did not result in such a differentiation. Conclusion We propose that cholesteatoma recurrence is based on TLR4 signalling imprinted in the cholesteatoma cells. It induces excessive inflammation of stem cells and fibroblasts, proliferation of perimatrix fibroblasts and the generation of epidermal cells from stem cells thru paracrine signalling by fibroblasts. Treatment of the operation site with a TLR4 antagonist might reduce the chance of cholesteatoma recurrence.

scholarly journals Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis

2009 ◽  
Vol 187 (1) ◽  
pp. 91-100 ◽  
Author(s):  
Alexandra Van Keymeulen ◽  
Guilhem Mascre ◽  
Khalil Kass Youseff ◽  
Itamar Harel ◽  
Cindy Michaux ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Embryonic Development ◽  
Lineage Tracing ◽  
Merkel Cells ◽  
Sensitive Area ◽  
Epidermal Stem Cells ◽  
Conditional Deletion ◽  
Slow Turnover ◽  
Dependent Mechanism

Merkel cells (MCs) are located in the touch-sensitive area of the epidermis and mediate mechanotransduction in the skin. Whether MCs originate from embryonic epidermal or neural crest progenitors has been a matter of intense controversy since their discovery >130 yr ago. In addition, how MCs are maintained during adulthood is currently unknown. In this study, using lineage-tracing experiments, we show that MCs arise through the differentiation of epidermal progenitors during embryonic development. In adults, MCs undergo slow turnover and are replaced by cells originating from epidermal stem cells, not through the proliferation of differentiated MCs. Conditional deletion of the Atoh1/Math1 transcription factor in epidermal progenitors results in the absence of MCs in all body locations, including the whisker region. Our study demonstrates that MCs arise from the epidermis by an Atoh1-dependent mechanism and opens new avenues for study of MC functions in sensory perception, neuroendocrine signaling, and MC carcinoma.

scholarly journals Chronic inflammation of middle ear cholesteatoma promotes its recurrence via a paracrine mechanism

2020 ◽  
Author(s):  
Matthias Schuermann ◽  
Felix Oppel ◽  
Senyao Shao ◽  
Verena Volland-Thurn ◽  
Christian Kaltschmidt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Middle Ear ◽  
Culture Conditions ◽  
Epidermal Differentiation ◽  
Epidermal Stem Cells ◽  
Middle Ear Cholesteatoma ◽  
Surgical Extraction ◽  
Standard Culture ◽  
Lps Treatment ◽  
Tlr4 Antagonist

Abstract BackgroundCholesteatoma disease is an expanding lesion in the middle ear. Hearing loss and facial paralysis alongside with other intracranial complications are found. No pharmaceutical treatment is available today and recurrence after surgical extraction occurs. We investigated possible TLR4-based mechanisms promoting recurrence and explore possible treatments strategies.MethodsWe isolated fibroblasts and epidermal stem cells from cholesteatoma tissue and healthy auditory canal skin. Subsequently, their expression under standard culture conditions and after stimulation with LPS was investigated by RT-qPCR. Cell metabolism and proliferation were analysed upon LPS treatment, with and without TLR4 antagonist. An indirect co-culture of fibroblasts and epidermal stem cells isolated from cholesteatoma tissue was utilized to monitor epidermal differentiation upon LPS treatment by RT-qPCR and immunocytochemistry.ResultsUnder standard culture conditions, we detected a tissue-independent higher expression of IL-1β and IL-8 in stem cells, an upregulation of KGF and IGF-2 in both cell types derived from cholesteatoma and higher expression of TLR4 in stem cells derived from cholesteatoma tissue. Upon LPS challenge, we could detect a significantly higher expression of IL-1α, IL-1β, IL-6 and IL-8 in stem cells and of TNF-a, GM-CSF and CXCL-5 in stem cells and fibroblasts derived from cholesteatoma. The expression of the growth factors KGF, EGF, EREG, IGF-2 and HGF was significantly higher in fibroblasts, particularly when derived from cholesteatoma. Upon treatment with LPS the metabolism was elevated in stem cells and fibroblasts, proliferation was only enhanced in fibroblasts derived from cholesteatoma. This could be reversed by the treatment with a TLR4 antagonist. The cholesteatoma fibroblasts could be triggered by LPS to promote the epidermal differentiation of the stem cells, while no LPS treatment or LPS treatment without the presence of fibroblasts did not result in such a differentiation.ConclusionWe propose that cholesteatoma recurrence is based on TLR4 signalling imprinted in the cholesteatoma cells. It induces excessive inflammation of stem cells and fibroblasts, proliferation of perimatrix fibroblasts and the generation of epidermal cells from stem cells thru paracrine signalling by fibroblasts. Treatment of the operation site with a TLR4 antagonist might reduce the chance of cholesteatoma recurrence.

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