Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: Implications on epithelial stem cells

Cell ◽  
1989 ◽  
Vol 57 (2) ◽  
pp. 201-209 ◽  
Author(s):  
George Cotsarelis ◽  
Shih-Zen Cheng ◽  
Gang Dong ◽  
Tung-Tien Sun ◽  
Robert M. Lavker
Keyword(s):  
Stem Cells ◽  
Basal Cells ◽  
Epithelial Stem Cells ◽  
Slow Cycling

scholarly journals Airway tissue stem cells reutilize the embryonic proliferation regulator, Tgfß-Id2 axis, for tissue regeneration

2020 ◽  
Author(s):  
Hirofumi Kiyokawa ◽  
Akira Yamaoka ◽  
Chisa Matsuoka ◽  
Tomoko Tokuhara ◽  
Takaya Abe ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Tissue Regeneration ◽  
Basal Cell ◽  
Molecular Mechanisms ◽  
Fine Tuning ◽  
Basal Cells ◽  
Adult Tissue ◽  
Epithelial Regeneration ◽  
Slow Cycling

SummaryDuring development, quiescent basal stem cells are derived from proliferative primordial progenitors through the cell cycle slowdown. In contrast, quiescent basal cells contribute to tissue repair during adult tissue regeneration by shifting from slow-cycling to proliferating and subsequently back to slow-cycling. Although sustained basal cell proliferation results in tumorigenesis, the molecular mechanisms regulating these transitions remain unknown. Using temporal single-cell transcriptomics of developing murine airway progenitors and in vivo genetic validation experiments, we found that Tgfß signaling slowed down cell cycle by inhibiting Id2 expression in airway progenitors and contributed to the specification of slow-cycling basal cell population during development. In adult tissue regeneration, reduced Tgfß signaling restored Id2 expression and initiated epithelial regeneration. Id2 overexpression and Tgfbr2 knockout enhanced epithelial proliferation; however, persistent Id2 expression in basal cells drove hyperplasia at a rate that resembled a precancerous state. Together, the Tgfß-Id2 axis commonly regulates the proliferation transitions in airway basal cells during development and regeneration, and its fine-tuning is critical for normal regeneration while avoiding basal cell hyperplasia.

scholarly journals Differentiation-related expression of a major 64K corneal keratin in vivo and in culture suggests limbal location of corneal epithelial stem cells.

1986 ◽  
Vol 103 (1) ◽  
pp. 49-62 ◽  
Author(s):  
A Schermer ◽  
S Galvin ◽  
T T Sun
Keyword(s):  
Stem Cells ◽  
Strong Support ◽  
Transitional Zone ◽  
Basal Cells ◽  
Epithelial Stem Cells ◽  
Corneal Epithelial ◽  
Differentiated Cells ◽  
Limbal Epithelium ◽  
Cell Layers

In this paper we present keratin expression data that lend strong support to a model of corneal epithelial maturation in which the stem cells are located in the limbus, the transitional zone between cornea and conjunctiva. Using a new monoclonal antibody, AE5, which is highly specific for a 64,000-mol-wt corneal keratin, designated RK3, we demonstrate that this keratin is localized in all cell layers of rabbit corneal epithelium, but only in the suprabasal layers of the limbal epithelium. Analysis of cultured corneal keratinocytes showed that they express sequentially three major keratin pairs. Early cultures consisting of a monolayer of "basal" cells express mainly the 50/58K keratins, exponentially growing cells synthesize additional 48/56K keratins, and postconfluent, heavily stratified cultures begin to express the 55/64K corneal keratins. Cell separation experiments showed that basal cells isolated from postconfluent cultures contain predominantly the 50/58K pair, whereas suprabasal cells contain additional 55/64K and 48/56K pairs. Basal cells of the older, postconfluent cultures, however, can become AE5 positive, indicating that suprabasal location is not a prerequisite for the expression of the 64K keratin. Taken together, these results suggest that the acidic 55K and basic 64K keratins represent markers for an advanced stage of corneal epithelial differentiation. The fact that epithelial basal cells of central cornea but not those of the limbus possess the 64K keratin therefore indicates that corneal basal cells are in a more differentiated state than limbal basal cells. These findings, coupled with the known centripetal migration of corneal epithelial cells, strongly suggest that corneal epithelial stem cells are located in the limbus, and that corneal basal cells correspond to "transient amplifying cells" in the scheme of "stem cells----transient amplifying cells----terminally differentiated cells."

scholarly journals Proximal location of mouse prostate epithelial stem cells

2002 ◽  
Vol 157 (7) ◽  
pp. 1257-1265 ◽  
Author(s):  
Akira Tsujimura ◽  
Yasuhiro Koikawa ◽  
Sarah Salm ◽  
Tetsuya Takao ◽  
Sandra Coetzee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Distal Region ◽  
Proximal Region ◽  
Proliferative Potential ◽  
Collagen Gels ◽  
Epithelial Stem Cells ◽  
Mouse Prostate ◽  
Slow Cycling ◽  
Prostatic Ducts

Stem cells are believed to regulate normal prostatic homeostasis and to play a role in the etiology of prostate cancer and benign prostatic hyperplasia. We show here that the proximal region of mouse prostatic ducts is enriched in a subpopulation of epithelial cells that exhibit three important attributes of epithelial stem cells: they are slow cycling, possess a high in vitro proliferative potential, and can reconstitute highly branched glandular ductal structures in collagen gels. We propose a model of prostatic homeostasis in which mouse prostatic epithelial stem cells are concentrated in the proximal region of prostatic ducts while the transit-amplifying cells occupy the distal region of the ducts. This model can account for many biological differences between cells of the proximal and distal regions, and has implications for prostatic disease formation.

Phosphorylation of Smad2/3 at the specific linker threonine residue indicates slow-cycling esophageal stem-like cells before re-entry to the cell cycle

2016 ◽  
Vol 29 (2) ◽  
pp. 1-8 ◽  
Author(s):  
Y. Takahashi ◽  
T. Fukui ◽  
M. Kishimoto ◽  
R. Suzuki ◽  
T. Mitsuyama ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Epithelial Cells ◽  
Light Microscope ◽  
Basal Layer ◽  
Immunofluorescent Staining ◽  
Epithelial Stem Cells ◽  
Significant Expression ◽  
Slow Cycling ◽  
Regeneration Phase

Summary The stem cell compartment in the esophageal epithelium is possibly located in the basal layer. We have identified significant expression of Smad2/3, phosphorylated at specific linker threonine residues (pSmad2/3L-Thr), in the epithelial cells of murine stomach and intestine, and have suggested that these cells are epithelial stem cells. In this study, we explore whether pSmad2/3L-Thr could serve as a biomarker for esophageal stem cells. We examined esophageal tissues from normal C57BL/6 mice and those with esophagitis. Double immunofluorescent staining of pSmad2/3L-Thr with Ki67, CDK4, p63, or CK14 was performed. After immunofluorescent staining, we stained the same sections with hematoxylin-eosin and observed these cells under a light microscope. We used the 5-bromo-2-deoxyuridine (BrdU) labeling assay to examine label retention of pSmad2/3L-Thr immunostaining-positive cells. We collected specimens 5, 10, 15 and 20 days after repeated BrdU administrations and observed double immunofluorescent staining of pSmad2/3L-Thr with BrdU. In the esophagus, pSmad2/3L-Thr immunostaining-positive cells were detected in the basal layer. These cells were detected between Ki67 immunostaining-positive cells, but they were not co-localized with Ki67. pSmad2/3L-Thr immunostaining-positive cells showed co-localization with CDK4, p63, and CK14. Under a light microscope, pSmad2/3L-Thr immunostaining-positive cells indicated undifferentiated morphological features. Until 20 days follow-up period, pSmad2/3L-Thr immunostaining-positive cells were co-localized with BrdU. pSmad2/3L-Thr immunostaining-positive cells significantly increased in the regeneration phase of esophagitis mucosae, as compared with control mice (esophagitis vs. control: 6.889 ± 0.676/cm vs. 4.293 ± 0.659/cm; P < 0.001). We have identified significant expression of pSmad2/3L-Thr in the specific epithelial cells of murine esophagi. We suggest that these cells are slow-cycling epithelial stem-like cells before re-entry to the cell cycle.

scholarly journals FGF10-FGFR2B Signaling Generates Basal Cells and Drives Alveolar Epithelial Regeneration by Bronchial Epithelial Stem Cells after Lung Injury

2019 ◽  
Vol 12 (5) ◽  
pp. 1041-1055 ◽  
Author(s):  
Tingting Yuan ◽  
Thomas Volckaert ◽  
Elizabeth F. Redente ◽  
Seantel Hopkins ◽  
Kylie Klinkhammer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Lung Injury ◽  
Basal Cells ◽  
Epithelial Stem Cells ◽  
Bronchial Epithelial ◽  
Alveolar Epithelial ◽  
Epithelial Regeneration

A subset of mouse tracheal epithelial basal cells generates large colonies in vitro

2004 ◽  
Vol 286 (4) ◽  
pp. L631-L642 ◽  
Author(s):  
Kelly G. Schoch ◽  
Adriana Lori ◽  
Kimberlie A. Burns ◽  
Tracy Eldred ◽  
John C. Olsen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
The Body ◽  
Growth Potential ◽  
Small Subset ◽  
Basal Cells ◽  
Airway Epithelial ◽  
Epithelial Stem Cells ◽  
Tracheal Epithelial Cells ◽  
Tracheal Epithelial

Airway epithelial stem cells are not well characterized. To examine clonal growth potential, we diluted single, viable B6.129S7-Gtrosa26 (Rosa26) mouse tracheal epithelial cells that constitutively express β-galactosidase into non-Rosa26 cells in an air-liquid interface cell culture model; 1.7% of the cells formed colonies of varying size, and, on average, 0.1% of the cells formed large colonies. Thus only a small subset of cells displayed progenitorial capacity suggestive of stem or early transient amplifying cells. Prior studies identified cells with high keratin 5 (K5) promoter activity in specific niches in the mouse trachea and these cells corresponded to the location of bromodeoxyuridine label-retaining cells, thought to be stem cells (Borthwick DW, Shahbazian M, Todd KQ, Dorin JR, and Randell SH, Am J Respir Cell Mol Biol: 24: 662–670, 2001). To explore the hypothesis that stem cells were present in the K5-expressing compartment, we created transgenic mice in which enhanced green fluorescent protein (EGFP) was driven by the K5 promoter. These mice expressed EGFP in most basal cells of the body including a subset of tracheal basal cells apparently located in positions similar to previously identified stem cell niches. Flow cytometrically purified EGFP-positive cells had an overall colony-forming efficiency 4.5-fold greater than EGFP-negative cells, but the ability to generate large colonies was 12-fold greater. Thus adult mouse tracheal epithelial cells with progenitorial capacity sufficient to generate large colonies reside in the basal cell compartment. These studies are a first step toward purification and characterization of airway epithelial stem cells.

scholarly journals Identification and isolation of human prostate epithelial stem cells based on α2β1-integrin expression

2001 ◽  
Vol 114 (21) ◽  
pp. 3865-3872 ◽  
Author(s):  
Anne T. Collins ◽  
Fouad K. Habib ◽  
Norman J. Maitland ◽  
David E. Neal
Keyword(s):  
Stem Cells ◽  
Type I Collagen ◽  
Specific Antigen ◽  
Basal Layer ◽  
Basement Membranes ◽  
Type I ◽  
Integrin Subunit ◽  
Basal Cells ◽  
Epithelial Stem Cells

A major impediment to our understanding of the biology of stem cells is the inability to distinguish them from their differentiating progeny. We made use of the known association of stem cells with basement membranes to isolate prostate epithelial stem cells. We show that, in vivo, putative stem cells express higher levels of the α2-integrin subunit than other cells within the basal layer. Approximately 1% of basal cells examined by confocal microscopy were integrin ‘bright’, and these cells can be selected directly from the tissue on the basis of rapid adhesion to type I collagen. This selected population has a basal phenotype, as determined by expression of CK5 and CK14 and lack of expression of the differentiation-specific markers prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), and has a fourfold greater ability to form colonies in vitro than the total basal population. These putative stem cells are distinguished from other basal cells by their ability to generate prostate-like glands in vivo with morphologic and immuno-histochemical evidence of prostate-specific differentiation. These properties are consistent with a stem cell origin. Furthermore, the presence of surface integrins on prostate stem cells suggests that these cells share common pathways with stem cells in other tissues.

A common mechanism links activities of butyrate in the colon

2017 ◽  
Author(s):  
Mohit S. Verma ◽  
Michael J. Fink ◽  
Gabriel L Salmon ◽  
Nadine Fornelos ◽  
Takahiro E. Ohara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Histone Deacetylases ◽  
Biological Activities ◽  
Short Chain Fatty Acids ◽  
Common Mechanism ◽  
Epithelial Stem Cells ◽  
Degree Of Unsaturation ◽  
Structure Activity ◽  
Starting Point ◽  
New Compounds

Two biological activities of butyrate in the colon (suppression of proliferation of colonic epithelial stem cells and inflammation) correlate with inhibition of histone deacetylases. Cellular and biochemical studies of molecules similar in structure to butyrate, but different in molecular details (functional groups, chain-length, deuteration, oxidation level, fluorination, or degree of unsaturation) demonstrated that these activities were sensitive to molecular structure, and were compatible with the hypothesis that butyrate acts by binding to the Zn<sup>2+</sup> in the catalytic site of histone deacetylases. Structure-activity relationships drawn from a set of 36 compounds offer a starting point for the design of new compounds targeting the inhibition of histone deacetylases. The observation that butyrate was more potent than other short-chain fatty acids is compatible with the hypothesis that crypts evolved (at least in part), to separate stem cells at the base of crypts from butyrate produced by commensal bacteria.

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