scholarly journals DCAMKL-1 Expression Identifies Tuft Cells Rather Than Stem Cells in the Adult Mouse Intestinal Epithelium

2009 ◽  
Vol 137 (6) ◽  
pp. 2179-2180 ◽  
Author(s):  
François Gerbe ◽  
Bénédicte Brulin ◽  
Leila Makrini ◽  
Catherine Legraverend ◽  
Philippe Jay
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lu Xue ◽  
Lingyu Bao ◽  
Julia Roediger ◽  
Yijun Su ◽  
Bingyin Shi ◽  
...  

Abstract Background Adult stem cells play an essential role in adult organ physiology and tissue repair and regeneration. While much has been learnt about the property and function of various adult stem cells, the mechanisms of their development remain poorly understood in mammals. Earlier studies suggest that the formation of adult mouse intestinal stem cells takes place during the first few weeks after birth, the postembryonic period when plasma thyroid hormone (T3) levels are high. Furthermore, deficiency in T3 signaling leads to defects in adult mouse intestine, including reduced cell proliferation in the intestinal crypts, where stem cells reside. Our earlier studies have shown that protein arginine methyltransferase 1 (PRMT1), a T3 receptor coactivator, is highly expressed during intestinal maturation in mouse. Methods We have analyzed the expression of PRMT1 by immunohistochemistry and studied the effect of tissue-specific knockout of PRMT1 in the intestinal epithelium. Results We show that PRMT1 is expressed highly in the proliferating transit amplifying cells and crypt base stem cells. By using a conditional knockout mouse line, we have demonstrated that the expression of PRMT1 in the intestinal epithelium is critical for the development of the adult mouse intestine. Specific removal of PRMT1 in the intestinal epithelium results in, surprisingly, more elongated adult intestinal crypts with increased cell proliferation. In addition, epithelial cell migration along the crypt-villus axis and cell death on the villus are also increased. Furthermore, there are increased Goblet cells and reduced Paneth cells in the crypt while the number of crypt base stem cells remains unchanged. Conclusions Our finding that PRMT1 knockout increases cell proliferation is surprising considering the role of PRMT1 in T3-signaling and the importance of T3 for intestinal development, and suggests that PRMT1 likely regulates pathways in addition to T3-signaling to affect intestinal development and/or homeostasis, thus affecting cell proliferating and epithelial turn over in the adult.


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.


2010 ◽  
Vol 17 (4) ◽  
pp. 498-505 ◽  
Author(s):  
Antonin Bukovsky

AbstractAt the beginning of the last century, reproductive biologists have discussed whether in mammalian species the fetal oocytes persist or are replaced by neo-oogenesis during adulthood. Currently the prevailing view is that neo-oogenesis is functional in lower vertebrates but not in mammalian species. However, contrary to the evolutionary rules, this suggests that females of lower vertebrates have a better opportunity to provide healthy offspring compared to mammals with oocytes subjected to environmental threats for up to several decades. During the last 15 years, a new effort has been made to determine whether the oocyte pool in adult mammals is renewed as well. Most recently, Ji Wu and colleagues reported a production of offspring from female germline stem cells derived from neonatal and adult mouse ovaries. This indicates that both neonatal and adult mouse ovaries carry stem cells capable of producing functional oocytes. However, it is unclear whether neo-oogenesis from ovarian somatic stem cells is physiologically involved in follicular renewal and why menopause occurs. Here we review observations that indicate an involvement of immunoregulation in physiological neo-oogenesis and follicular renewal from ovarian stem cells during the prime reproductive period and propose why menopause occurs in spite of persisting ovarian stem cells.


2018 ◽  
Vol 154 (1) ◽  
pp. S48-S49
Author(s):  
Claartje A. Meddends ◽  
Edward E.S. Nieuwenhuis ◽  
Michal Mokry

2021 ◽  
Author(s):  
Zayna Chaker ◽  
Corina Segalada ◽  
Fiona Doetsch

Neural stem cells (NSCs) in the adult mouse brain contribute to lifelong brain plasticity. NSCs in the adult ventricular-subventricular zone (V-SVZ) are heterogeneous and, depending on their location in the niche, give rise to different subtypes of olfactory bulb interneurons. Here, we show that during pregnancy multiple regionally-distinct NSCs are dynamically recruited at different times. Coordinated temporal activation of these NSC pools generates sequential waves of short-lived olfactory bulb interneuron subtypes that mature in the mother around birth and in the perinatal care period. Concomitant with neuronal addition, oligodendrocyte progenitors also transiently increase in the olfactory bulb. Thus, life experiences, such as pregnancy, can trigger transient neurogenesis and gliogenesis under tight spatial and temporal control, and may provide a novel substrate for brain plasticity in anticipation of temporary physiological demand.


2011 ◽  
Vol 208 (2) ◽  
pp. 285-294 ◽  
Author(s):  
Shuichiro Takashima ◽  
Masanori Kadowaki ◽  
Kazutoshi Aoyama ◽  
Motoko Koyama ◽  
Takeshi Oshima ◽  
...  

Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation (BMT), and damage to the gastrointestinal (GI) tract plays a critical role in amplifying systemic disease. Intestinal stem cells (ISCs) play a pivotal role not only in physiological tissue renewal but also in regeneration of the intestinal epithelium after injury. In this study, we have discovered that pretransplant conditioning regimen damaged ISCs; however, the ISCs rapidly recovered and restored the normal architecture of the intestine. ISCs are targets of GVHD, and this process of ISC recovery was markedly inhibited with the development of GVHD. Injection of Wnt agonist R-spondin1 (R-Spo1) protected against ISC damage, enhanced restoration of injured intestinal epithelium, and inhibited subsequent inflammatory cytokine cascades. R-Spo1 ameliorated systemic GVHD after allogeneic BMT by a mechanism dependent on repair of conditioning-induced GI tract injury. Our results demonstrate for the first time that ISC damage plays a central role in amplifying systemic GVHD; therefore, we propose ISC protection by R-Spo1 as a novel strategy to improve the outcome of allogeneic BMT.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Albert Spicher ◽  
Andrea Meinhardt ◽  
Marc-Estienne Roehrich ◽  
Giuseppe Vassalli

Identification of stem cells based on hematopoietic stem cell (HSC) surface markers, such as stem cell antigen-1 (Sca-1) and the c-kit receptor, has limited specificity. High aldehyde-dehydrogenase (ALDH) activity is a general cellular property of stem cells shared by HSC, neural, and intestinal stem cells. The presence of cells with high ALDH activity in the adult heart has not been investigated. Methods: Cells were isolated from adult mouse hearts, and from atrial appendage samples from humans with ischemic or valvular heart disease. Myocyte-depleted mouse Sca-1+, and lineage (Lin)-negative/c-kit+ human heart cells were purified with immunomagnetic beads. ALDH-high cells were identified using a specific fluorescent substrate, and sorted by FACS. Cell surface marker analysis was performed by flow cytometry. Results: Myocyte-depleted mouse heart cells contained 4.8+/−3.2% ALDH-high/SSC-low and 32.6+/−1.6% Sca-1+ cells. ALDH-high cells were Lin-negative, Sca-1+ CD34+ CD105+ CD106+, contained small CD44+ (27%) and CD45+ (15%) subpopulations, and were essentially negative for c-kit (2%), CD29, CD31, CD133 and Flk-1. After several passages in culture, ~20% of ALDH-high cells remained ALDH-high. Myocyte-depleted human atrial cells contained variable numbers of ALDH-high cells ranging from 0.5% to 11%, and 4% Lin-negative/c-kit+ cells. ALDH-high cells were CD29+ CD105+, contained a small c-kit+ subpopulation (5%), and were negative for CD31, CD45 and CD133. After 5 passages in culture, the majority of ALDH-high cells remained ALDH-high. Conclusions: Adult mouse and human hearts contain significant numbers of cells with high ALDH activity, a general cellular property that stem cells possess in different organs, and express stem cell markers (Sca-1 and CD34 in the mouse). The immunophenotype of cardiac-resident ALDH-high cells differs from that previously described for bone marrow ALDH-high HSC, and suggests that this cell population may be enriched in mesenchymal progenitors. Analysis of lineage differentiation potential of ALDH-high cells is in progress. ALDH activity provides a new, practical approach to purifying cardiac-resident progenitor cells.


Reproduction ◽  
2021 ◽  
Author(s):  
Shinnosuke Suzuki ◽  
John R. McCarrey ◽  
Brian P Hermann

Initiation of spermatogonial differentiation in the mouse testis begins with the response to retinoic acid (RA) characterized by activation of KIT and STRA8 expression. In the adult, spermatogonial differentiation is spatiotemporally coordinated by a pulse of RA every 8.6 days that is localized to stages VII-VIII of the seminiferous epithelial cycle. Dogmatically, progenitor spermatogonia that express retinoic acid receptor gamma (RARG) at these stages will differentiate in response to RA, but this has yet to be tested functionally. Previous single-cell RNA-seq data identified phenotypically and functionally distinct subsets of spermatogonial stem cells (SSCs) and progenitor spermatogonia, where late progenitor spermatogonia were defined by expression of RARG and Dppa3. Here, we found late progenitor spermatogonia (RARGhigh KIT-) were further divisible into two subpopulations based on Dppa3 reporter expression (Dppa3-ECFP or Dppa3-EGFP) and were observed across all stages of the seminiferous epithelial cycle. However, nearly all Dppa3+ spermatogonia were differentiating (KIT+) late in the seminiferous epithelial cycle (stages X-XII), while Dppa3- late progenitors remained abundant, suggesting that Dppa3+ and Dppa3- late progenitors differentially responded to RA. Following acute RA treatment (2-4hr), significantly more Dppa3+ late progenitors induced KIT, including at the midpoint of the cycle (stages VI-IX), than Dppa3- late progenitors. Subsequently, single-cell analyses indicated a subset of Dppa3+ late progenitors expressed higher levels of Rxra, which we confirmed by RXRA whole-mount immunostaining. Together, these results indicate RARG alone is insufficient to initiate a spermatogonial response to RA in the adult mouse testis and suggest differential RXRA expression may discriminate responding cells.


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