scholarly journals Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium

2011 ◽  
Vol 192 (5) ◽  
pp. 767-780 ◽  
Author(s):  
François Gerbe ◽  
Johan H. van Es ◽  
Leila Makrini ◽  
Bénédicte Brulin ◽  
Georg Mellitzer ◽  
...  

The unique morphology of tuft cells was first revealed by electron microscopy analyses in several endoderm-derived epithelia. Here, we explore the relationship of these cells with the other cell types of the intestinal epithelium and describe the first marker signature allowing their unambiguous identification. We demonstrate that although mature tuft cells express DCLK1, a putative marker of quiescent stem cells, they are post-mitotic, short lived, derive from Lgr5-expressing epithelial stem cells, and are found in mouse and human tumors. We show that whereas the ATOH1/MATH1 transcription factor is essential for their differentiation, Neurog3, SOX9, GFI1, and SPDEF are dispensable, which distinguishes these cells from enteroendocrine, Paneth, and goblet cells, and raises from three to four the number of secretory cell types in the intestinal epithelium. Moreover, we show that tuft cells are the main source of endogenous intestinal opioids and are the only epithelial cells that express cyclooxygenase enzymes, suggesting important roles for these cells in the intestinal epithelium physiopathology.

Blood ◽  
1970 ◽  
Vol 35 (6) ◽  
pp. 761-774 ◽  
Author(s):  
BERNARD S. MORSE ◽  
NICHOLAS J. RENCRICCA ◽  
FREDERICK STOHLMAN

Abstract Hydroxyurea, a cytotoxic agent that kills cells in DNA synthesis, was used to study the relationship between erythropoietin and the generative cycle of the immediate erythroid precursor cell. When OHU and EP were administered simultaneously to hypertransfused mice, the resultant erythroid response was diminished relative to EP treated controls. OHU given at intervals after EP resulted in a progressively greater diminution of erythroid response. From these studies, then, we would suggest that in the suppressed animal the committed stem cell compartment is in cycle but with a prolonged G1. After EP there is a shortening of the generation time and an increase in the rate of turnover of the committed stem cells. The data also indicate that cells in cycle are differentiated into the pronormoblast compartment. It further may be suggested that erythropoietin is effective throughout the bulk of the generative cycle although it seems unlikely that differentiation is accomplished during the mitotic phase. Whether erythropoietin must be present in both G1 and S as suggested by Kretchmar cannot be answered by the present studies. The data also indicate that cells of the pluripotential compartment are normally in G0 or perhaps a prolonged G1. Damage to the committed compartment appears to be in part repaired by the influx of cells from the pluripotential compartment.


Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 560
Author(s):  
Yoojin Seo ◽  
So-Yeon Park ◽  
Hyung-Sik Kim ◽  
Jeong-Seok Nam

Despite endogenous insults such as mechanical stress and danger signals derived from the microbiome, the intestine can maintain its homeostatic condition through continuous self-renewal of the crypt–villus axis. This extraordinarily rapid turnover of intestinal epithelium, known to be 3 to 5 days, can be achieved by dynamic regulation of intestinal stem cells (ISCs). The crypt base-located leucine-rich repeat-containing G-protein-coupled receptor 5-positive (Lgr5+) ISCs maintain intestinal integrity in the steady state. Under severe damage leading to the loss of conventional ISCs, quiescent stem cells and even differentiated cells can be reactivated into stem-cell-like cells with multi-potency and contribute to the reconstruction of the intestinal epithelium. This process requires fine-tuning of the various signaling pathways, including the Hippo–YAP system. In this review, we summarize recent advances in understanding the correlation between Hippo–YAP signaling and intestinal homeostasis, repair, and tumorigenesis, focusing specifically on ISC regulation.


2009 ◽  
Vol 137 (6) ◽  
pp. 2179-2180 ◽  
Author(s):  
François Gerbe ◽  
Bénédicte Brulin ◽  
Leila Makrini ◽  
Catherine Legraverend ◽  
Philippe Jay

2020 ◽  
Vol 52 (7) ◽  
pp. 723-735 ◽  
Author(s):  
Yuanzhuo Gu ◽  
Xin Zheng ◽  
Junfang Ji

Abstract Cancer stem cells (CSCs) are cells possessing abilities of self-renewal, differentiation, and tumorigenicity in NOD/SCID mice. Based on this definition, multiple cell surface markers (such as CD24, CD133, CD90, and EpCAM) as well as chemical methods are discovered to enrich liver CSCs in the recent decade. Accumulated studies have revealed molecular signatures and signaling pathways involved in regulating different liver CSCs. Among liver CSCs positive for different markers, some molecular features and regulatory pathways are commonly shared, while some are only unique in certain CSC populations. These studies imply that liver CSCs exhibit diverse heterogeneity, while a functional relationship also exists. The aim of this review is to revisit the society of liver CSCs and summarize the common or unique molecular features of known liver CSCs. We hope to call for attention of researchers on the relationship of the liver CSC subgroups and to provide clues on the hierarchical structure of the liver CSC society.


Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769224 ◽  
Author(s):  
Ioannis A Voutsadakis

Proteasome is a multi-protein organelle that participates in cellular proteostasis by destroying damaged or short-lived proteins in an organized manner guided by the ubiquitination signal. By being in a central place in the cellular protein complement homeostasis, proteasome is involved in virtually all cell processes including decisions on cell survival or death, cell cycle, and differentiation. These processes are important also in cancer, and thus, the proteasome is an important regulator of carcinogenesis. Cancers include a variety of cells which, according to the cancer stem cell theory, descend from a small percentage of cancer stem cells, alternatively termed tumor-initiating cells. These cells constitute the subsets that have the ability to propagate the whole variety of cancer and repopulate tumors after cytostatic therapies. Proteasome plays a role in cellular processes in cancer stem cells, but it has been found to have a decreased function in them compared to the rest of cancer cells. This article will discuss the transcriptional regulation of proteasome sub-unit proteins in cancer and in particular cancer stem cells and the relationship of the proteasome with the pluripotency that is the defining characteristic of stem cells. Therapeutic opportunities that present from the understanding of the proteasome role will also be discussed.


2009 ◽  
Vol 296 (2) ◽  
pp. C296-C305 ◽  
Author(s):  
S. Samuel ◽  
R. Walsh ◽  
J. Webb ◽  
A. Robins ◽  
C. Potten ◽  
...  

Colonic epithelial stem cells are believed to be located at the crypt base where they have previously been shown to express musashi-1. The colonic stem cell niche, which includes extracellular matrix and myofibroblasts (together with other cell types), is likely to be important in maintaining the function of the progenitor cells. The aims of our studies were to characterize stem cells in isolated and disaggregated human colonic crypt epithelial cells and investigate their interactions with monolayers of primary human colonic myofibroblasts. In unfractionated preparations of disaggregated colonic crypts, musashi-1 positive cells preferentially adhered to colonic myofibroblasts, despite the presence of excess blocking anti-β1-integrin antibody. These adherent epithelial cells remained viable for a number of days and developed slender processes. Cells with side population characteristics (as demonstrated by ability to expel the dye Hoechst 33342) were consistently seen in the isolated colonic crypt epithelial cells. These side population cells expressed musashi-1, β1-integrin, BerEP4, and CD133. Sorted side population crypt epithelial cells also rapidly adhered to primary colonic myofibroblasts. In conclusion, in preparation of isolated and disaggregated human colonic crypts, cells with stem cell characteristics preferentially adhere to primary human colonic myofibroblasts in a β1-integrin-independent fashion.


2013 ◽  
Vol 66 (03) ◽  
Author(s):  
Jan Adamowicz ◽  
Marta Pokrywczyńska ◽  
Jakub Tworkiewicz ◽  
Zbigniew Wolski ◽  
Tomasz Drewa

Author(s):  
Anna A. Valyaeva ◽  
Anastasia A. Zharikova ◽  
Artem S. Kasianov ◽  
Yegor S. Vassetzky ◽  
Eugene V. Sheval

AbstractSARS-CoV-2 can infiltrate the lower respiratory tract, resulting in severe respiratory failure and a high death rate. Normally, the airway and alveolar epithelium can be rapidly reconstituted by multipotent stem cells after episodes of infection. Here, we analyzed published RNA-seq datasets and demonstrated that cells of four different lung epithelial stem cell types express SARS-CoV-2 entry factors, including Ace2. Thus, stem cells can be potentially infected by SARS-CoV-2, which may lead to defects in regeneration capacity partially accounting for the severity of SARS-CoV-2 infection and its consequences.


1988 ◽  
Vol 90 (2) ◽  
pp. 237-245
Author(s):  
J.M. Lord ◽  
J.A. Thick ◽  
C.M. Bunce ◽  
A.M. Taylor ◽  
P.H. Gallimore ◽  
...  

The monoclonal antibody AGF2.3 identifies a nuclear envelope protein that is restricted to certain cell types. In particular, this antigen shows a reduced level of expression during haemopoietic cell maturation. In this study, we have examined the relationship of this protein to known nuclear envelope proteins that have a similar molecular mass. Antigen extraction and immunoelectron microscope studies revealed that the AGF2.3 protein is an integral membrane protein present at both the inner and outer aspects of the nuclear envelope. The protein is not associated with nuclear pores and therefore is distinct from pore complex proteins. The AGF2.3 protein does not have ATPase activity. Therefore, this protein is also distinct from a myosin heavy chain-like ATPase that is associated with the nuclear envelope. The AGF2.3 antibody identifies a novel nuclear envelope protein. Further studies of the biochemical nature of the AGF2.3 protein should provide insight into novel cellular processes at the nuclear envelope relating to the lineage or maturation status of cells.


Lipids ◽  
1971 ◽  
Vol 6 (1) ◽  
pp. 58-61 ◽  
Author(s):  
Stuart Patton ◽  
T. W. Keenan

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