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Physiological and pathological role of local and immigrating colonic stem cells

World Journal of gastroenterology 2012年第4期18卷 295-301页

作者： Ferenc Sipos gábor valcz Béla Molnár 2nd Department of Internal Medicine Semmelweis University Molecular Medicine Research Unit Hungarian Academy of Sciences

The latest avenue of research is revealing the existence of and role for the colonic stem cells in the physiological renewal of the mucosa and in pathological circumstanc- es where they have both positive and negative effects. In the case of human colon, different levels of stem cell compartments exist. First, the crypt epithelial stem cells, which have a role in the normal crypt epithelial cell dynamics and in colorectal carcinogenesis. Close to the crypts, the second layer of stern cells can be found; the local subepithelial stem cell niche, including the pericryptic subepithelial myofibroblasts that regulate the epithelial cell differentiation and have a crucial role in cancer progression and chronic inflammation-related fibrosis. The third level of stem cell compartment is the immigrating bone-marrow-derived stem cells, which have an important role in wound healing after severe mucosal inflammation, but are also involved in cancer invasion. This paper focuses on stem cell biology in the context of physiological and pathological processes in the human colon.

关键词： Colon Mesencyhmal stem cells Bone marrow Myofibroblast Fibrosis Colorectal cancer Para-thyroid hormone Transforming growth factor-β

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World Journal of gastroenterology 2016年第47期22卷 10325-10340页

作者： Orsolya galamb Alexandra Kalmár Barbara Kinga Barták árpád V Patai Katalin Leiszter Bálint Péterfia Barnabás Wichmann gábor valcz gábor Veres Zsolt Tulassay Béla Molnár Molecular Medicine Research group Hungarian Academy of Sciences 2~(nd) Department of Internal Medicine Semmelweis University 1~(st) Department of Paediatrics Semmelweis University

AIM To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock Cpg sites. METHODS In silico DNA methylation analysis of 353 epigenetic clock Cp g sites published by Steve Horvath was performed using methylation array data for a set of 123 colonic tissue samples [64 colorectal cancer(CRC), 42 adenoma, 17 normal; gEO accession number: gSE48684]. Among the differentially methylated agerelated genes, secreted frizzled related protein 1(SFRP1) promoter methylation was further investigated in colonic tissue from 8 healthy adults, 19 normal children, 20 adenoma and 8 CRC patients using bisulfite-specific PCR followed by methylation-specific high resolution melting(MS-HRM) analysis. m RNA expression of age-related "epigenetic clock" genes was studied using Affymetrix HgU133 Plus2.0 whole transcriptome data of 153 colonic biopsy samples(49 healthy adult, 49 adenoma, 49 CRC, 6 healthy children)(gEO accession numbers: gSE37364, gSE10714, gSE4183, gSE37267). Whole promoter methylation analysis of genes showing inverse DNA methylationgene expression data was performed on 30 colonic samples using methyl capture *** Fifty-seven age-related Cp g sites including hypermethylated PPP1R16 B, SFRP1, SYNE1 and hypomethylated MgP, PIPOX were differentially methylated between CRC and normal tissues(P g sites differed significantly, including hypermethylated DKK3, SDC2, SFRP1, SYNE1 and hypomethylated CEMIP, SPATA18(P gion was significantly hypermethylated in CRC(55.0% ± 8.4 %) and adenoma tissue samples(49.9% ± 18.1%) compared to normal adult(5.2% ± 2.7%) and young(2.2% ± 0.7%) colonic tissue(P ghtly, but significantly increased in healthy adults compared to normal young samples(P gnificantly increased S

关键词： DNA methylation Aging Colorectal cancer Adenoma Epigenetic drift Epigenetic clock Secreted frizzled related protein 1

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Association of hepatocyte-derived growth factor receptor/caudal type homeobox 2 co-expression with mucosal regeneration in active ulcerative colitis

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World Journal of gastroenterology 2015年第28期21卷 8569-8579页

作者： Ferenc Sipos Miklós Constantinovits gábor valcz Zsolt Tulassay gy?rgyi M?zes 2nd Department of Internal Medicine Semmelweis University Molecular Medicine Research group Hungarian Academy of Sciences

AIM:To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor(HgFR)-expressing cells in active ulcerative colitis(UC).METHODS:On the whole 38 peripheral blood samples and 38 colonic biopsy samples from 18 patients with histologically proven active UC and 20 healthy control subjects were *** preparing tissue microarrays and blood smears HgFR,caudal type homeobox 2(CDX2),prominin-1(CD133) and Musashi-1conventional and double fluorescent immunolabelings were *** samples were digitalized using high-resolution Mirax Desk instrument,and analyzed with the Mirax TMA Module *** semiquantitative counting of immunopositive lamina propria(LP) cells 5 fields of view were counted at magnification x 200 in each sample core,then mean ± SD were *** case of peripheral blood smears,30 fields of view with 100 μm diameter were evaluated in every sample and the number of immunopositive cells(mean ± SD) was *** 337 nm UVA Laser MicroDissection system at least 5000 subepithelial cells from the lamina propria were *** expression analysis of HgFR,CDX2,CD133,leucine-rich repeat-containing g-protein coupled receptor 5(Lgr5),Musashi-1 and cytokeratin20(CK20) were performed in both laser-microdisscted samples and blood samples by using real time reverse transcription polymerase chain reaction(RT-PCR).RESULTS:By performing conventional and double fluorescent immunolabelings confirmed by RT-PCR,higher number of HgFR(blood:6.7 ± 1.22 vs 38.5 ±3.18;LP:2.25 ± 0.85 vs 9.22 ± 0.65;P < 0.05),CDX2(blood:0 vs 0.94 ± 0.64;LP:0.75 ± 0.55 vs 2.11± 0.75;P < 0.05),CD133(blood:1.1 ± 0.72 vs 8.3± 1.08;LP:11.1 ± 0.85 vs 26.28 ± 1.71;P < 0.05)and Musashi-1(blood and LP:0 vs scattered) positive cells were detected in blood and lamina propria of UC samples as compared to ***/CDX2(blood:0 vs 1± 0.59;LP:0.8 ± 0.69 vs 2.06 ± 0.72,P < 0.05)and Musashi-1/CDX2(blood and LP:0 vs sc

关键词： Hepatocyte-derived growth factor receptor Caudal type homeobox 2 CD133 Musashi-1 Leucinerichrepeat-containing g-protein coupled receptor 5 Ulcerative colitis Regeneration

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