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.

55 INFLUENCE OF DONOR CELL TYPE ON THE DEVELOPMENT OF PORCINE NUCLEAR TRANSFER EMBRYOS

2006 ◽  
Vol 18 (2) ◽  
pp. 136
Author(s):  
K. Lee ◽  
W. L. Fodor ◽  
Z. Machaty
Keyword(s):  
Stem Cells ◽  
Olfactory Bulb ◽  
Progenitor Cells ◽  
Nuclear Transfer ◽  
Cell Types ◽  
Blastocyst Stage ◽  
Blastocyst Formation ◽  
Developmental Potential ◽  
Differentiated Cells ◽  
Fetal Fibroblasts

Embryonic development after nuclear transfer is very low; the majority of cloned embryos do not survive the pre-implantation stage. Recent reports indicate that the characteristics of nuclear transfer embryos depend on the type of nuclear donor cells. It has been suggested that development after nuclear transfer improves if less differentiated cells are used as nuclear donors. The aim of the present study was to investigate the developmental potential of nuclear transfer embryos reconstructed using differentiated and non-differentiated cells. Two types of non-differentiated cells, skin stem cells and olfactory bulb progenitor cells, were used; fetal fibroblasts were used as differentiated control. Prior to nuclear transfer, the differentiated state of the cells was characterized by Oct-4 immunocytochemistry (Chemicon International, Inc., Temecula, CA, USA); Oct-4 is known to be expressed by pluripotent cells only. During nuclear transfer, the cells were transferred into the perivitelline space of in vitro-matured enucleated oocytes. After fusion, reconstructed oocytes were activated by an electrical pulse followed by incubation in 10 �g/mL cycloheximide and 5 �g/mL cytochalasin B for 5 h. The embryos were subsequently cultured in NCSU-23 medium for 6 days; their developmental data were recorded and compared by ANOVA. Non-differentiated cell types showed strong Oct-4 expression, whereas the marker protein was completely absent in fetal fibroblast cells. A total of 161 embryos were reconstructed using skin stem cells, 171 embryos from olfactory bulb progenitor cells, and 189 embryos from fibroblasts. Of the skin stem cell-derived embryos, 32.9% cleaved, and during subsequent culture, 5.6% developed to the morula/blastocyst stage. In the olfactory bulb progenitor cell group, 19.8% cleaved, and the percentage of embryos that developed to the morula/blastocyst stage was 4.7%. In the control group, 22.7% cleaved; the morula/blastocyst formation was 2.6%. Embryos reconstructed from skin stem cells showed superior cleavage rate compared to embryos from the other cell types (P < 0.05). Also, morula/blastocyst formation from skin stem cells was significantly higher than that from fetal fibroblasts (P < 0.05), and morula/blastocyst formation from olfactory bulb progenitor cell-derived embryos also tended to be higher compared to control embryos (P = 0.08). Furthermore, the formation of morulae/blastocysts per cleaved embryos was the highest in embryos reconstructed with olfactory bulb progenitor cells (23.5% vs. 17.0% using skin stem cells and 11.6% using fibroblasts) implying that embryos from olfactory bulb progenitor cells may have higher developmental potential in later stages of development. The results demonstrate that nuclei of different donor cells support development to various degrees and confirm previous reports that using non-differentiated cells as nuclear donors increases the efficiency of nuclear transfer in the pig.

Advances of Stem Cell Therapy to Treat Heart Failure

Nano LIFE ◽  
2019 ◽  
Vol 09 (03) ◽  
pp. 1941002
Author(s):  
Yanbin Fu ◽  
Zhiying He ◽  
Chao Zhang
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Stem Cell Therapy ◽  
Cell Types ◽  
Differentiated Cells ◽  
Novel Strategy

Stem cell therapy is being developed as a promising novel strategy for the treatment of heart-associated diseases. Several types of cells such as skeletal myoblasts, bone marrow (BM) mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), adipose stem cells (ADSCs), cardiac progenitor cells (CPCs), induced pluripotent stem cells (iPSCs) have been tested in pre-clinical and clinical cardiac repairing models. Fibroblasts, as terminally differentiated cells, could also be trans-differentiated into cardiomyocytes in vitro. In this review, we will summarize the recent advances of cell types, potential applications and challenges of stem cell therapy in the treatment of heart failure.

Extruded Nucleoli in Poorly Differentiated Dental Pulp Cells of Human Frontal Teeth

2018 ◽  
Author(s):  
Mugurel Constantin Rusu ◽  
Adelina Maria Jianu ◽  
Rodica Lighezan ◽  
Roxana Oancea ◽  
Vasile Sorin Manoiu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Dental Pulp ◽  
Cell Types ◽  
Differentiated Cells ◽  
Nucleolar Proteins ◽  
Human Dental Pulp ◽  
Pulp Cells ◽  
Bona Fide ◽  
Poorly Differentiated

All tissues are known to contain stem cells niches. The dental pulp stem cells (DPSCs) are highly proliferative and can differentiate to various cell types, including endothelial cells. We aimed to evaluate the ultrastructural characteristics of the human dental pulp niche corresponding to the frontal teeth. We found bona fide quiescent DPSCs with high nucleoplasmic ratios, as well as poorly differentiated cells with increased amount of cytoplasm, these later being indicated as dental pulp progenitor cells (DPPCs). Vasculogenic cords were built up by mitotic endothelial progenitor cells with a peculiar trait: giant nucleoli extruded within the cytoplasm. They were either partly embedded within the nuclei, case in which their adnuclear side was coated by marginal heterochromatin and the abnuclear side was coated by a thin rim of ribosomes, or were completely isolated from the nuclei, being covered by ribosomes and surrounded by cytoplasmic fragments of chromatin. To our knowledge such giant extruded nucleoli were not previously reported in any human stem niche or cell type, although similar evidence was gathered in other species as well as in plants. They relate perhaps to intermediate stages of differentiation within the dental niche, thus appearing as transient structures. Their role needs further investigations as it looks that not only nucleolar proteins are exported into the cytoplasm, but the entire nucleolus could be extruded.

scholarly journals Cellular Functions of OCT-3/4 Regulated by Ubiquitination in Proliferating Cells

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 663
Author(s):  
Kwang-Hyun Baek ◽  
Jihye Choi ◽  
Chang-Zhu Pei
Keyword(s):  
Stem Cells ◽  
Cellular Proliferation ◽  
Critical Role ◽  
Embryonic Stem ◽  
Cell Types ◽  
Ubiquitin Proteasome System ◽  
Specific Cell ◽  
Cellular Mechanisms ◽  
Proliferating Cells ◽  
Proliferation And Differentiation

Octamer-binding transcription factor 3/4 (OCT-3/4), which is involved in the tumorigenesis of somatic cancers, has diverse functions during cancer development. Overexpression of OCT-3/4 has been detected in various human somatic tumors, indicating that OCT-3/4 activation may contribute to the development and progression of cancers. Stem cells can undergo self-renewal, pluripotency, and reprogramming with the help of at least four transcription factors, OCT-3/4, SRY box-containing gene 2 (SOX2), Krüppel-like factor 4 (KLF4), and c-MYC. Of these, OCT-3/4 plays a critical role in maintenance of undifferentiated state of embryonic stem cells (ESCs) and in production of induced pluripotent stem cells (iPSCs). Stem cells can undergo partitioning through mitosis and separate into specific cell types, three embryonic germ layers: the endoderm, the mesoderm, and the trophectoderm. It has been demonstrated that the stability of OCT-3/4 is mediated by the ubiquitin-proteasome system (UPS), which is one of the key cellular mechanisms for cellular homeostasis. The framework of the mechanism is simple, but the proteolytic machinery is complicated. Ubiquitination promotes protein degradation, and ubiquitination of OCT-3/4 leads to regulation of cellular proliferation and differentiation. Therefore, it is expected that OCT-3/4 may play a key role in proliferation and differentiation of proliferating cells.

scholarly journals me31B regulates stem cell homeostasis by preventing excess dedifferentiation in the Drosophila male germline

2021 ◽  
Author(s):  
Lindy Jensen ◽  
Zsolt G. Venkei ◽  
George J. Watase ◽  
Bitarka Bisai ◽  
Scott Pletcher ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Critical Role ◽  
Stem Cell Population ◽  
Germline Stem Cells ◽  
Cell Identity ◽  
Stem Cell Maintenance ◽  
Differentiated Cells ◽  
Male Germline ◽  
Elevated Frequency

Tissue-specific stem cells maintain tissue homeostasis by providing a continuous supply of differentiated cells throughout the life of organisms. Differentiated/differentiating cells can revert back to a stem cell identity via dedifferentiation to help maintain the stem cell pool beyond the lifetime of individual stem cells. Although dedifferentiation is important to maintain the stem cell population, it is speculated to underlie tumorigenesis. Therefore, this process must be tightly controlled. Here we show that a translational regulator me31B plays a critical role in preventing excess dedifferentiation in the Drosophila male germline: in the absence of me31B, spermatogonia (SGs) dedifferentiate into germline stem cells (GSCs) at a dramatically elevated frequency. Our results show that the excess dedifferentiation is likely due to misregulation of nos, a key regulator of germ cell identity and GSC maintenance. Taken together, our data reveal negative regulation of dedifferentiation to balance stem cell maintenance with differentiation.

Lineage potential, plasticity and environmental reprogramming of epithelial stem/progenitor cells

2014 ◽  
Vol 42 (3) ◽  
pp. 637-644 ◽  
Author(s):  
Alessandro W. Amici ◽  
Fatai O. Onikoyi ◽  
Paola Bonfanti
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Cell Therapy ◽  
Hair Follicle ◽  
Progenitor Cells ◽  
Environmental Cues ◽  
Full Potential ◽  
Thymic Epithelium ◽  
Differentiated Cells ◽  
Stratified Epithelia

Recent evidence supports and reinforces the concept that environmental cues may reprogramme somatic cells and change their natural fate. In the present review, we concentrate on environmental reprogramming and fate potency of different epithelial cells. These include stratified epithelia, such as the epidermis, hair follicle, cornea and oesophagus, as well as the thymic epithelium, which stands alone among simple and stratified epithelia, and has been shown recently to contain stem cells. In addition, we briefly discuss the pancreas as an example of plasticity of intrinsic progenitors and even differentiated cells. Of relevance, examples of plasticity and fate change characterize pathologies such as oesophageal metaplasia, whose possible cell origin is still debated, but has important implications as a pre-neoplastic event. Although much work remains to be done in order to unravel the full potential and plasticity of epithelial cells, exploitation of this phenomenon has already entered the clinical arena, and might provide new avenues for future cell therapy of these tissues.

scholarly journals Adaptation to oxygen deprivation in cultures of human pluripotent stem cells, endothelial progenitor cells, and umbilical vein endothelial cells

2010 ◽  
Vol 298 (6) ◽  
pp. C1527-C1537 ◽  
Author(s):  
Hasan Erbil Abaci ◽  
Rachel Truitt ◽  
Eli Luong ◽  
German Drazer ◽  
Sharon Gerecht
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Oxygen Consumption ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Cellular Responses ◽  
Glut 1 ◽  
Lower Oxygen ◽  
Oxygen Tensions

Hypoxia plays an important role in vascular development through hypoxia-inducible factor-1α (HIF-1α) accumulation and downstream pathway activation. We sought to explore the in vitro response of cultures of human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs), human endothelial progenitor cells (hEPCs), and human umbilical cord vein endothelial cells (HUVECs) to normoxic and hypoxic oxygen tensions. We first measured dissolved oxygen (DO) in the media of adherent cultures in atmospheric (21% O2), physiological (5% O2), and hypoxic oxygen conditions (1% O2). In cultures of both hEPCs and HUVECs, lower oxygen consumption was observed when cultured in 1% O2. At each oxygen tension, feeder-free cultured hESCs and iPSCs were found to consume comparable amounts of oxygen. Transport analysis revealed that the oxygen uptake rate (OUR) of hESCs and iPSCs decreased distinctly as DO availability decreased, whereas the OUR of all cell types was found to be low when cultured in 1% O2, demonstrating cell adaptation to lower oxygen tensions by limiting oxygen consumption. Next, we examined HIF-1α accumulation and the expression of target genes, including VEGF and angiopoietins ( ANGPT; angiogenic response), GLUT-1 (glucose transport), BNIP3, and BNIP3L (autophagy and apoptosis). Accumulations of HIF-1α were detected in all four cell lines cultured in 1% O2. Corresponding upregulation of VEGF, ANGPT2, and GLUT-1 was observed in response to HIF-1α accumulation, whereas upregulation of ANGPT1 was detected only in hESCs and iPSCs. Upregulation of BNIP3 and BNIP3L was detected in all cells after 24-h culture in hypoxic conditions, whereas apoptosis was not detectable using flow cytometry analysis, suggesting that BNIP3 and BNIP3L can lead to cell autophagy rather than apoptosis. These results demonstrate adaptation of all cell types to hypoxia but different cellular responses, suggesting that continuous measurements and control over oxygen environments will enable us to guide cellular responses.

scholarly journals Rapid and sustained hematopoietic recovery in lethally irradiated mice transplanted with purified Thy-1.1lo Lin-Sca-1+ hematopoietic stem cells

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3758-3779 ◽  
Author(s):  
N Uchida ◽  
HL Aguila ◽  
WH Fleming ◽  
L Jerabek ◽  
IL Weissman
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Blood Cells ◽  
Critical Role ◽  
White Blood Cells ◽  
Cell Types ◽  
Dose Dependence ◽  
Hematopoietic Stem ◽  
Hematopoietic Recovery

Abstract Hematopoietic stem cells (HSCs) are believed to play a critical role in the sustained repopulation of all blood cells after bone marrow transplantation (BMT). However, understanding the role of HSCs versus other hematopoietic cells in the quantitative reconstitution of various blood cell types has awaited methods to isolate HSCs. A candidate population of mouse HSCs, Thy-1.1lo Lin-Sca-1+ cells, was isolated several years ago and, recently, this population has been shown to be the only population of BM cells that contains HSCs in C57BL/Ka-Thy-1.1 mice. As few as 100 of these cells can radioprotect 95% to 100% of irradiated mice, resulting long-term multilineage reconstitution. In this study, we examined the reconstitution potential of irradiated mice transplanted with purified Thy-1.1lo Lin-Sca-1+ BM cells. Donor-derived peripheral blood (PB) white blood cells were detected as early as day 9 or 10 when 100 to 1,000 Thy-1.1lo Lin-Sca-1+ cells were used, with minor dose-dependent differences. The reappearance of platelets by day 14 and thereafter was also seen at all HSC doses (100 to 1,000 cells), with a slight dose-dependence. All studied HSC doses also allowed RBC levels to recover, although at the 100 cell dose a delay in hematocrit recovery was observed at day 14. When irradiated mice were transplanted with 500 Thy-1.1lo Lin-Sca-1+ cells compared with 1 x 10(6) BM cells (the equivalent amount of cells that contain 500 Thy-1.1lo Lin-Sca-1+ cells as well as progenitor and mature cells), very little difference in the kinetics of recovery of PB, white blood cells, platelets, and hematocrit was observed. Surprisingly, even when 200 Thy1.1lo Lin-Sca- 1+ cells were mixed with 4 x 10(5) Sca-1- BM cells in a competitive repopulation assay, most of the early (days 11 and 14) PB myeloid cells were derived from the HSC genotype, indicating the superiority of the Thy-1.1lo Lin-Sca-1+ cells over Sca-1- cells even in the early phases of myeloid reconstitution. Within the Thy-1.1lo Lin-Sca-1+ population, the Rhodamine 123 (Rh123)hi subset dominates in PB myeloid reconstitution at 10 to 14 days, only to be overtaken by the Rh123lo subset at 3 weeks and thereafter. These findings indicate that HSCs can account for the early phase of hematopoietic recovery, as well as sustained hematopoiesis, and raise questions about the role of non-HSC BM populations in the setting of BMT.

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."

miRNA Profiling of Pediatric ALL and Non-Hodgkin Lymphomas.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2719-2719
Author(s):  
Pablo Landgraf ◽  
Amanda Rice ◽  
Nicola Iovino ◽  
Valerio Fulci ◽  
Robert Sheridan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Lines ◽  
Burkitt Lymphoma ◽  
Lymphoblastic Leukemia ◽  
Expression Patterns ◽  
Critical Role ◽  
Mrna Translation ◽  
Cell Types ◽  
Two Samples ◽  
Hematopoetic Stem Cells

Abstract MicroRNAs (miRNAs) are conserved 21−23 nt non-coding RNA molecules that regulate gene expression either by mRNA cleavage or by repression of mRNA translation. miRNAs regulate many different processes, including apoptosis and cell proliferation and may therefore also play a critical role in oncogenic transformation. To date, most miRNAs have been discovered by cDNA cloning and sequencing, though other profiling methods, such as miRNA micro-arrays, have recently been applied. Profiling of miRNA expression by cloning has the advantage of identifying new miRNA genes, and if a large number of clones are sequenced, to also be quantitative. In addition the exact sequence is determined and polymorphisms and mutations in any miRNAs can readily be detected. To get an insight in the role of miRNAs in the differentiation and maturation of hematopoetic cells as well as their contribution to oncogenesis in ALL and lymphomas, we cloned and sequenced various cell lines and patient samples:five cell lines (B-ALL, AML, Burkitt Lymphoma); samples from sorted blood cells covering pluripotent stem cells, B-, T-, NK- cells, monocytes and granulocytes; eight patient samples with ALL (2 pro-B-ALL, 2 pre-B-ALL, 2 cALL, 2 T-ALL) at the time point of diagnosis; four additional samples of these patients with B-ALL and two samples of T-ALL patients each after 36 days of treatment according to the protocol of the German Cooperative Acute Lymphoblastic Leukemia study group (COALL-07-03). We also recorded the small RNA profiles of three patients with various forms of AML at diagnosis and after the first induction according to the protocol of the AML-BFM 2004 study; two Burkitt lymphoma samples and one B-Non Hodgkin Lymphoma (B-NHL) sample. We report here the identification of over 20 novel human miRNAs in these samples. To determine specific expression patterns, the miRNA profiles were compared to a reference set of 22 different human tissue types. Some miRNAs are expressed in a cell or tissue specific manner, others have a more general expression pattern between different cell types and tissues. For example human miRNA miR-142 is ubiquitously expressed in cells of the hematopoetic lineage, whereas human miR-150 is only expressed in differentiated hematopoetic cells, but not in hematopoetic stem cells. In hematopoetic stem cells human miR-126 is 3 to more than 10 times higher expressed than in differentiated hematopoetic cells. The existence of the latter two in humans are first described in this study. miR-16 on the other hand is expressed in all cell types examined including non-hematopoetic. Furthermore, miRNAs are up/down-regulated in ALL and NHL patient samples. In conclusion, this study identifies miRNAs that might be involved in hematopoetic cell differentiation and maturation and is important to identify miRNAs that might contribute to oncogenesis in leukemia and lymphomas.

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