scholarly journals The spatial transcriptomic landscape of the healing intestine following damage

2021 ◽  
Author(s):  
Sara M Parigi ◽  
Ludvig Larsson ◽  
Srustidhar Das ◽  
Ricardo Omar Ramirez Flores ◽  
Annika Frede ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Practice ◽  
Steady State ◽  
Intestinal Barrier ◽  
Mucosal Healing ◽  
Complex Cell ◽  
Epithelial Stem Cells ◽  
Cell Network ◽  
P53 Activation ◽  
Murine Colon

The intestinal barrier is composed of a complex cell network defining highly compartmentalized and specialized structures. Here, we use spatial transcriptomics (ST) to define how the transcriptomic landscape is spatially organized in the steady state and healing murine colon. At steady state conditions, we demonstrate a previously unappreciated molecular regionalization of the colon, which dramatically changes during mucosal healing. Here, we identified spatially-organized transcriptional programs defining compartmentalized mucosal healing, and regions with dominant wired pathways. Furthermore, we showed that decreased p53 activation defined areas with increased presence of proliferating epithelial stem cells. Finally, we used our resource to map transcriptomics modules associated with human diseases demonstrating that ST can be used to inform clinical practice. Overall, we provide a publicly available resource defining principles of transcriptomic regionalization of the colon during mucosal healing and a framework to develop and progress further hypotheses.

scholarly journals Qingchang Wenzhong Decoction Accelerates Intestinal Mucosal Healing Through Modulation of Dysregulated Gut Microbiome, Intestinal Barrier and Immune Responses in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhongmei Sun ◽  
Junxiang Li ◽  
Wenting Wang ◽  
Yuyue Liu ◽  
Jia Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Mucosal Healing ◽  
Intestinal Stem Cells ◽  
Mucosal Inflammation ◽  
Protective Effects ◽  
Fecal Microbiome ◽  
Epithelial Regeneration

Inflammatory bowel disease (IBD), a group of multifactorial and inflammatory infirmities, is closely associated with dysregulation of gut microbiota and host metabolome, but effective treatments are currently limited. Qingchang Wenzhong Decoction (QCWZD) is an effective and classical traditional herbal prescription for the treatment of IBD and has been proved to attenuate intestinal inflammation in a model of acute colitis. However, the role of QCWZD in recovery phase of colitis is unclear. Here, we demonstrated that mice treated with QCWZD showed a faster recovery from dextran sulfate sodium (DSS)-induced epithelial injury, accompanied by reduced mucosal inflammation and attenuated intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing compared to those receiving sterile water. The protective effects of QCWZD are gut microbiota dependent, as demonstrated by fecal microbiome transplantation and antibiotics treatment. Gut microbes transferred from QCWZD-treated mice displayed a similar role in mucosal protection and epithelial regeneration as QCWZD on colitis in mice, and depletion of the gut microbiota through antibiotics treatments diminished the beneficial effects of QCWZD on colitis mice. Moreover, metabolomic analysis revealed metabolic profiles alternations in response to the gut microbiota reprogrammed by QCWZD intervention, especially enhanced tryptophan metabolism, which may further accelerate intestinal stem cells-mediated epithelial regeneration to protect the integrity of intestinal mucosa through activation of Wnt/β-catenin signals. Collectively, our results suggested that orally administrated QCWZD accelerates intestinal mucosal healing through the modulation of dysregulated gut microbiota and metabolism, thus regulating intestinal stem cells-mediated epithelial proliferation, and hold promise for novel microbial-based therapies in the treatment of IBD.

scholarly journals Senescence of alveolar stem cells drives progressive pulmonary fibrosis

2019 ◽  
Author(s):  
Changfu Yao ◽  
Xiangrong Guan ◽  
Gianni Carraro ◽  
Tanyalak Parimon ◽  
Xue Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Chronic Disease ◽  
Pulmonary Fibrosis ◽  
Cellular Senescence ◽  
Adult Mouse ◽  
Alveolar Type ◽  
Epithelial Stem Cells ◽  
Organ Function ◽  
P53 Activation

AbstractTissue fibrosis is a common pathological outcome of chronic disease that markedly impairs organ function leading to morbidity and mortality. In the lung, idiopathic pulmonary fibrosis (IPF) is an insidious and fatal interstitial lung disease associated with declining pulmonary function. Here, we show that alveolar type 2 (AT2) stem cells isolated from IPF lung tissue exhibit characteristic transcriptomic features of cellular senescence. We used conditional loss of Sin3a in adult mouse AT2 cells to initiate a program of p53-dependent cellular senescence, AT2 cell depletion, and spontaneous, progressive pulmonary fibrosis. We establish that senescence rather than loss of epithelial stem cells serves as a proximal driver of Tgfβ activation and progressive fibrosis and show that either genetic or pharmacologic interventions targeting p53 activation, senescence, or downstream Tgfβ activation, block fibrogenesis.

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.

scholarly journals Stem Cells in the Path of Light, from Corneal to Retinal Reconstruction

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 873
Author(s):  
Ovidiu Samoila ◽  
Lacramioara Samoila
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Clinical Success ◽  
Corneal Stroma ◽  
Cell Transplant ◽  
Inclusion Criteria ◽  
Epithelial Stem Cells ◽  
Corneal Epithelial ◽  
Stem Cells Transplantation ◽  
Limbal Epithelial Stem Cells

The future of eye reconstruction invariably includes stem cells transplantation. Corneal limbus, corneal stroma, trabeculum, retinal cells, optic nerve, and all structures that are irreversibly damaged and have no means to be repaired or replaced, through conventional treatment or surgery, represent targets for stem cell reconstruction. This review tries to answer the question if there is any clinical validation for stem therapies, so far, starting from the cornea and, on the path of light, arriving to the retina. The investigation covers the last 10 years of publications. From 2385 published sources, we found 56 clinical studies matching inclusion criteria, 39 involving cornea, and 17 involving retina. So far, corneal epithelial reconstruction seems well validated clinically. Enough clinical data are collected to allow some form of standardization for the stem cell transplant procedures. Cultivated limbal epithelial stem cells (CLET), simple limbal epithelial transplant (SLET), and oral mucosa transplantation are implemented worldwide. In comparison, far less patients are investigated in retinal stem reconstructions, with lower anatomical and clinical success, so far. Intravitreal, subretinal, and suprachoroidal approach for retinal stem therapies face specific challenges.

scholarly journals Long-term repopulating hematopoietic stem cells and “side population” in human steady state peripheral blood

2013 ◽  
Vol 11 (1) ◽  
pp. 625-633 ◽  
Author(s):  
Philippe Brunet de la Grange ◽  
Marija Vlaski ◽  
Pascale Duchez ◽  
Jean Chevaleyre ◽  
Veronique Lapostolle ◽  
...  
Keyword(s):  
Stem Cells ◽  
Steady State ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Side Population ◽  
Hematopoietic Stem
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