scholarly journals Diverse epithelial cell populations contribute to the regeneration of secretory units in injured salivary glands

Development ◽  
2020 ◽  
Vol 147 (19) ◽  
pp. dev192807
Author(s):  
Ninche Ninche ◽  
Mingyu Kwak ◽  
Soosan Ghazizadeh
Keyword(s):  
Salivary Glands ◽  
De Novo ◽  
Cell Types ◽  
Myoepithelial Cells ◽  
Lineage Tracing ◽  
Secretory Cells ◽  
Cell Populations ◽  
Cellular Plasticity ◽  
Ductal Cells ◽  
Differentiated Cells

ABSTRACTSalivary glands exert exocrine secretory function to provide saliva for lubrication and protection of the oral cavity. Its epithelium consists of several differentiated cell types, including acinar, ductal and myoepithelial cells, that are maintained in a lineage-restricted manner during homeostasis or after mild injuries. Glandular regeneration following a near complete loss of secretory cells, however, may involve cellular plasticity, although the mechanism and extent of such plasticity remain unclear. Here, by combining lineage-tracing experiments with a model of severe glandular injury in the mouse submandibular gland, we show that de novo formation of acini involves induction of cellular plasticity in multiple non-acinar cell populations. Fate-mapping analysis revealed that, although ductal stem cells marked by cytokeratin K14 and Axin2 undergo a multipotency switch, they do not make a significant contribution to acinar regeneration. Intriguingly, more than 80% of regenerated acini derive from differentiated cells, including myoepithelial and ductal cells, that appear to dedifferentiate to a progenitor-like state before re-differentiation into acinar cells. The potential of diverse cell populations serving as a reserve source for acini widens the therapeutic options for hyposalivation.

scholarly journals Diverse Epithelial Cell Populations Contribute to Regeneration of Secretory Units in Injured Salivary Glands

2020 ◽  
Author(s):  
Ninche Ninche ◽  
Mingyu Kwak ◽  
Soosan Ghazizadeh
Keyword(s):  
Stem Cells ◽  
Salivary Glands ◽  
De Novo ◽  
Cell Types ◽  
Myoepithelial Cells ◽  
Lineage Tracing ◽  
Secretory Cells ◽  
Cell Populations ◽  
Cellular Plasticity ◽  
Ductal Cells

ABSTRACTSalivary glands exert exocrine secretory function to provide saliva for lubrication and protection of the oral cavity. Its epithelium consists of several differentiated cell types including acinar, ductal and myoepithelial cells that are maintained in a lineage-restricted manner during homeostasis or after mild injuries. Glandular regeneration following a near complete loss of secretory cells, however, may involve cellular plasticity, although the mechanism and extent of such plasticity remain unclear. Here, by combining lineage-tracing experiments with a model of severe glandular injury in the mouse submandibular gland, we show that de novo formation of secretory units involves induction of cellular plasticity in multiple non-acinar cell populations. Fate-mapping analysis revealed that although ductal stem cells marked by cytokeratin K14 and Axin2 undergo a multipotency switch, they do not make a significant contribution to acinar regeneration. Intriguingly, more than 80% of regenerated acini derive from differentiated cells including myoepithelial and ductal cells that dedifferentiate to a progenitor-like state before redifferentiation to acinar cells. The potential of diverse cell populations serving as a reserve source for acini widens the therapeutic options for hyposalivation.SummarySalivary glands rely in recruitment of committed and fully differentiated cell populations as well as stem cells to ensure rapid regeneration and recovery of secretory cells.

scholarly journals Large organized chromatin lysine domains help distinguish primitive from differentiated cell populations

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Seyed Ali Madani Tonekaboni ◽  
Benjamin Haibe-Kains ◽  
Mathieu Lupien
Keyword(s):  
Transposable Elements ◽  
Histone Modifications ◽  
Cell Types ◽  
Regulatory Elements ◽  
Cell Populations ◽  
Genomic Features ◽  
Differentiated Cells ◽  
Chromatin Interactions ◽  
Topologically Associating Domains ◽  
Highly Expressed Genes

AbstractThe human genome is partitioned into a collection of genomic features, inclusive of genes, transposable elements, lamina interacting regions, early replicating control elements and cis-regulatory elements, such as promoters, enhancers, and anchors of chromatin interactions. Uneven distribution of these features within chromosomes gives rise to clusters, such as topologically associating domains (TADs), lamina-associated domains, clusters of cis-regulatory elements or large organized chromatin lysine (K) domains (LOCKs). Here we show that LOCKs from diverse histone modifications discriminate primitive from differentiated cell types. Active LOCKs (H3K4me1, H3K4me3 and H3K27ac) cover a higher fraction of the genome in primitive compared to differentiated cell types while repressive LOCKs (H3K9me3, H3K27me3 and H3K36me3) do not. Active LOCKs in differentiated cells lie proximal to highly expressed genes while active LOCKs in primitive cells tend to be bivalent. Genes proximal to bivalent LOCKs are minimally expressed in primitive cells. Furthermore, bivalent LOCKs populate TAD boundaries and are preferentially bound by regulators of chromatin interactions, including CTCF, RAD21 and ZNF143. Together, our results argue that LOCKs discriminate primitive from differentiated cell populations.

Transdifferentiation of pancreatic ductal cells to endocrine β-cells

2008 ◽  
Vol 36 (3) ◽  
pp. 353-356 ◽  
Author(s):  
Susan Bonner-Weir ◽  
Akari Inada ◽  
Shigeru Yatoh ◽  
Wan-Chun Li ◽  
Tandy Aye ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Duct Cell ◽  
Cell Types ◽  
Lineage Tracing ◽  
Β Cells ◽  
Partial Pancreatectomy ◽  
Pancreatic Cell ◽  
Ductal Cells ◽  
Pancreatic Ductal Cells

The regenerative process in the pancreas is of particular interest, since diabetes, whether Type 1 or Type 2, results from an inadequate amount of insulin-producing β-cells. Islet neogenesis, or the formation of new islets, seen as budding of hormone-positive cells from the ductal epithelium, has long been considered to be one of the mechanisms of normal islet growth after birth and in regeneration, and suggested the presence of pancreatic stem cells. Results from the rat regeneration model of partial pancreatectomy led us to hypothesize that differentiated pancreatic ductal cells were the pancreatic progenitors after birth, and that with replication they regressed to a less differentiated phenotype and then could differentiate to form new acini and islets. There are numerous supportive results for this hypothesis of neogenesis, including the ability of purified primary human ducts to form insulin-positive cells budding from ducts. However, to rigorously test this hypothesis, we took a direct approach of genetically marking ductal cells using CAII (carbonic anhydrase II) as a duct-cell-specific promoter to drive Cre recombinase in lineage-tracing experiments using the Cre-Lox system. We show that CAII-expressing pancreatic cells act as progenitors that give rise to both new islets and acini after birth and after injury (ductal ligation). This identification of a differentiated pancreatic cell type as an in vivo progenitor for all differentiated pancreatic cell types has implications for a potential expandable source for new islets for replenishment therapy for diabetes either in vivo or ex vivo.

Characterization of mammary cells from the lactating rat by electron microscopy

1978 ◽  
Vol 36 (2) ◽  
pp. 560-561
Author(s):  
P. Sadhukhan ◽  
J. Chakraborty ◽  
M. S. Soloff ◽  
M. H. Wieder ◽  
D. Senitzer
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Cell Types ◽  
Myoepithelial Cells ◽  
Mammary Tissue ◽  
Secretory Cells ◽  
Isolated Cells ◽  
Transmission Electron ◽  
Cell Processes ◽  
Phosphatase Cytochemistry

The means to identify cells isolated from the mammary gland of the lactating rat as a prerequisite for cell purification have been developed.The cells were isolated from mammary tissue with 0. 1% collagenase, and they were visualized by scanning and transmission electron microscopy and by alkaline phosphatase cytochemistry.The milk-secreting cells have surface microvilli, whereas the surface of the myoepithelial cells is smooth (Fig. 1). The two isolated epithelial cell types are readily distinguishable by transmission electron microscopy (Fig. 2). The secretory cells contain vacuoles and a relatively extensive rough endoplasmic reticulum, whereas the myoepithelial cells contain a more osmiophilic cytoplasm, contractile filaments (Fig. 3) and elongate processes. These features are consistent with the appearance of the two cell types in situ.Incubation of isolated cells with oxytocin prior to glutaraldehyde fixation resulted in the contraction of the myoepithelial cell processes (Figs. 4 & 5). This physiological response to oxytocin shows that the isolated myoepithelial cells were intact. The appearance of isolated secretory cells was unchanged by the presence of oxytocin.

Direct in vivo adenovirus-mediated gene transfer to salivary glands

1994 ◽  
Vol 266 (6) ◽  
pp. G1146-G1155 ◽  
Author(s):  
A. Mastrangeli ◽  
B. O'Connell ◽  
W. Aladib ◽  
P. C. Fox ◽  
B. J. Baum ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Gene Transfer ◽  
Salivary Glands ◽  
De Novo ◽  
Recombinant Adenovirus ◽  
Salivary Gland Cell ◽  
Immunodeficient Mice ◽  
Ductal Cells ◽  
Adenovirus Vectors

Gene transfer to the salivary glands holds the potential for the therapy of salivary gland disorders and for delivery of therapeutic proteins to the mouth and upper gastrointestinal tract. Administration of the recombinant adenovirus vectors Ad.RSV beta gal [coding for the intracellular protein beta-galactosidase (beta-Gal)] and Ad alpha 1AT [coding for human alpha 1-antitrypsin (alpha 1-AT), a secreted protein] to salivary gland cell lines in vitro demonstrated exogenous gene expression. Retrograde ductal injection of the Ad.RSV beta gal vector to rat salivary glands in vivo resulted in beta-Gal expression in acinar and ductal cells. Exposure of submandibular glands in vivo to Ad alpha 1AT resulted in expression of alpha 1-AT mRNA transcripts, de novo synthesis of alpha 1-AT, and secretion in the saliva. To evaluate the feasibility of adenovirus-mediated gene transfer to human glands, human minor salivary glands were infected ex vivo with Ad.RSV beta gal, and implanted into severe combined immunodeficient mice. Evaluation of the human tissue demonstrated beta-Gal activity. These observations demonstrate that adenovirus vectors are capable of direct delivery of genes to the salivary glands, suggesting a variety of possible gene therapy applications.

Epithelial-Myoepithelial Carcinoma of Salivary Glands

1992 ◽  
Vol 101 (6) ◽  
pp. 540-542 ◽  
Author(s):  
John G. Batsakis ◽  
Adel K. El-Naggar ◽  
Mario A. Luna
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Cell Population ◽  
Phenotypic Expression ◽  
Myoepithelial Cells ◽  
Salivary Gland Neoplasms ◽  
Myoepithelial Carcinoma ◽  
Parotid Glands ◽  
Ductal Cells ◽  
Epithelial Myoepithelial Carcinoma

Epithelial-myoepithelial carcinomas comprise approximately 1 % of all salivary gland neoplasms. They are preponderantly tumors of the parotid glands with a relatively low mortality but a decided locoregional aggressiveness. Histopathologically, the carcinomas are characterized by a dual cell population of epithelial (ductal) cells and myoepithelial cells. These cells vary in their dominance and phenotypic expression

scholarly journals Mapping the evolving landscape of super-enhancers during cell differentiation

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yan Kai ◽  
Bin E. Li ◽  
Ming Zhu ◽  
Grace Y. Li ◽  
Fei Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Differentiation ◽  
Target Gene ◽  
Target Genes ◽  
De Novo ◽  
Cell Types ◽  
Functional Enrichment ◽  
Target Gene Expression ◽  
Differentiated Cells ◽  
Super Enhancer

Abstract Background Super-enhancers are clusters of enhancer elements that play critical roles in the maintenance of cell identity. Current investigations on super-enhancers are centered on the established ones in static cell types. How super-enhancers are established during cell differentiation remains obscure. Results Here, by developing an unbiased approach to systematically analyze the evolving landscape of super-enhancers during cell differentiation in multiple lineages, we discover a general trend where super-enhancers emerge through three distinct temporal patterns: conserved, temporally hierarchical, and de novo. The three types of super-enhancers differ further in association patterns in target gene expression, functional enrichment, and 3D chromatin organization, suggesting they may represent distinct structural and functional subtypes. Furthermore, we dissect the enhancer repertoire within temporally hierarchical super-enhancers, and find enhancers that emerge at early and late stages are enriched with distinct transcription factors, suggesting that the temporal order of establishment of elements within super-enhancers may be directed by underlying DNA sequence. CRISPR-mediated deletion of individual enhancers in differentiated cells shows that both the early- and late-emerged enhancers are indispensable for target gene expression, while in undifferentiated cells early enhancers are involved in the regulation of target genes. Conclusions In summary, our analysis highlights the heterogeneity of the super-enhancer population and provides new insights to enhancer functions within super-enhancers.

Salivary Glands: A Paradigm for Diversity of Gland Development

1997 ◽  
Vol 8 (1) ◽  
pp. 51-75 ◽  
Author(s):  
P.C. Denny ◽  
W.D. Ball ◽  
R.S. Redman
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Expression Patterns ◽  
Cell Types ◽  
Secretory Cells ◽  
Control Mechanisms ◽  
Regulatory Cascade ◽  
Late Initiation ◽  
Cellular Phenotypes ◽  
Gland Development

The major salivary glands of mammals are represented by three pairs of organs that cooperate functionally to produce saliva for the oral cavity. While each type of gland produces a signature secretion that complements the secretions from the other glands, there is also redundancy as evidenced by secretion of functionally similar and, in some cases, identical products in the three glands. This, along with their common late initiation of development, in fetal terms, their similarities in developmental pattern, and their proximate sites of origin, suggests that a common regulatory cascade may have been shared until shortly before the onset of overt gland development. Furthermore, occasional ectopic differentiation of individual mature secretory cells in the "wrong" gland suggests that control mechanisms responsible for the distinctive cellular composition of each gland also share many common steps, with only minor differences providing the impetus for diversification. To begin to address this area, we examine here the origins of the salivary glands by reviewing the expression patterns of several genes with known morphogenetic potential that may be involved based on developmental timing and location. The possibility that factors leading to determination of the sites of mammalian salivary gland development might be homologous to the regulatory cascade leading to salivary gland formation in Drosophila is also evaluated. In a subsequent section, cellular phenotypes of neonatal and adult glands are compared and evaluated for insights into the mechanisms and lineages leading to cellular diversification. Finally, the phenomena of proliferation, repair, and regeneration in adult salivary glands are reviewed, with emphasis on the extent to which the cellular diversity is reversible and which cell type other than stem cells has the ability to redifferentiate into other cell types.

scholarly journals Immunocytochemical identification of proliferating cell types in mouse mammary gland.

1990 ◽  
Vol 38 (11) ◽  
pp. 1541-1547 ◽  
Author(s):  
A Sapino ◽  
L Macrì ◽  
P Gugliotta ◽  
G Bussolati
Keyword(s):  
Cell Proliferation ◽  
Mammary Gland ◽  
Smooth Muscle Actin ◽  
Cell Types ◽  
Myoepithelial Cells ◽  
Mouse Mammary Gland ◽  
Staining Procedure ◽  
Secretory Cells ◽  
Alpha Smooth Muscle Actin

To study cell proliferation in different cell types and segments of the mammary gland, we devised a dual staining procedure, combining nuclear labeling by 5-bromo-2'-deoxy-uridine (BrdU) uptake (revealed by a dark-brown precipitate) and an alternative (red or blue) cytoplasmic labeling by antibodies specific for the differentiation proteins of epithelial, myoepithelial, and secretory cell types. The following markers, revealed by APAAP or beta-galactosidase procedure, were selected: alpha-smooth muscle actin for the myoepithelial cells, keratin (detected by AE1 monoclonal) for the luminal epithelial cells, alpha-lactalbumin and beta-casein for the secretory cells. To follow the full process of organogenesis, the study was conducted in mouse mammary glands from virgin, primed, and lactating animals and from glands cultured in vitro under specific hormone stimulation. Cell proliferation was localized mainly in focal areas (end buds), and mostly corresponded to "null" undifferentiated cells. Estrogen and progestin stimulation induced a relative increase of proliferating differentiated cells of either epithelial or myoepithelial type, localized in ducts and alveolar structures. Prolactin stimulation induced proliferation in secretory cells.

scholarly journals Prom1 expression does not mark a stem/progenitor population in the mouse oviduct epithelium

2020 ◽  
Author(s):  
Matthew J Ford ◽  
Yojiro Yamanaka
Keyword(s):  
Stem Cell ◽  
Adult Stem Cell ◽  
Lineage Tracing ◽  
Stem Cell Marker ◽  
Secretory Cells ◽  
Cell Populations ◽  
Cell Marker ◽  
Multiciliated Cells ◽  
Cell Property ◽  
Stem Cell Populations

SummaryThe oviduct or fallopian tube is the site of fertilization and preimplantation embryonic development. The epithelium lining the oviduct consists of multiciliated and secretory cells, which support fertilization and preimplantation development, however, its homeostasis still remains poorly understood. CD133/Prom1 has been used to identify adult stem cell populations in various organs and often associated with cancer stem cell property. Using a Cre-recombinase based lineage tracing strategy, we found that CD133/Prom1 expression was not associated with a stem/progenitor population in the oviduct but marked a sub population of multiciliated and secretory cells which did not propagate. Interestingly, Prom1 expressing secretory cells rapidly transition to multiciliated cells and progressively migrate to the tips of epithelial folds in the ampulla. Our results show that CD133/Prom1 expression cannot be used as a progenitor/stem cell marker in the mouse oviduct.

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