A Glis3-CD133-Wnt signaling axis regulating the self-renewal of adult murine pancreatic progenitor-like cells in colonies/organoids
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA514382 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8432300.fastq.gz | Fastqsanger.gz | |||
| SRR8432295.fastq.gz | Fastqsanger.gz | |||
| SRR8432296.fastq.gz | Fastqsanger.gz | |||
| SRR8432297.fastq.gz | Fastqsanger.gz | |||
| SRR8432298.fastq.gz | Fastqsanger.gz |
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Project description:Adult pancreatic progenitor cells are a potential source of renewable insulin producing cells that can be used in regenerative medicine and cell replacement therapy for type-1 diabetes. We sought to understand the mechanisms by which adult pancreatic progenitor cells undergo self-renewal. The effects of knockdown of Glis3, CD133 (Prominin-1) and beta-catenin were investigated and we found that Glis3 and CD133 are capable of regulating self-renewal through Wnt gene expression.
2019-06-30 | GSE124944 | GEO
Project description:The existence and regenerative potential of resident stem and progenitor cells in the adult pancreas are controversial topics. A question that has been only minimally addressed is the capacity of a progenitor cell to self-renew, a key attribute that defines stem cells. Previously, our laboratory has identified putative stem and progenitor cells from the adult murine pancreas. Using an ex vivo colony/organoid culture system, we demonstrated that these stem/progenitor-like cells have self-renewal and multilineage differentiation potential. We have named these cells pancreatic colony-forming units (PCFUs) because they can give rise to three-dimensional colonies. However, the molecular mechanisms by which PCFUs self-renew have remained largely unknown. Here, we tested the hypothesis that PCFU self-renewal requires GLIS family zinc finger 3 (GLIS3), a zinc-finger transcription factor important in pancreas development. Pancreata from 2- to 4-month-old mice were dissociated, sorted for CD133highCD71low ductal cells, known to be enriched for PCFUs, and virally transduced with shRNAs to knock down GLIS3 and other proteins. We then plated these cells into our colony assays and analyzed the resulting colonies for protein and gene expression. Our results revealed a previously unknown GLIS3-to-CD133-to-WNT signaling axis in which GLIS3 and CD133 act as factors necessary for maintaining WNT receptors and signaling molecules in colonies, allowing responses to WNT ligands. Additionally, we found that CD133, but not GLIS3 or WNT, is required for phosphoinositide 3-kinase (PI3K)/AKT Ser/Thr kinase (AKT)-mediated PCFU survival. Collectively, our results uncover a molecular pathway that maintains self-renewal of adult murine PCFUs.
| S-EPMC6851293 | biostudies-literature
Project description:We show that Glis3 is expressed in gonocytes, SSCs and SPCs, but not in differentiated spermatogonia or subsequent stages of spermatogenesis nor in Sertoli or Leydig cells. We further demonstrate that Glis3-deficiency causes a severe impairment in spermatogenesis in mice. Although the number of gonocytes was slightly diminished in Glis3KO testis, the number undifferentiated, PLZF+ spermatogonia was dramatically reduced leading to a virtual block in the progression of spermatogenesis. Gene expression profiling showed that the expression of a number of genes associated with self-renewal and differentiation of spermatogonial cells was significantly decreased in 1-week-old Glis3KO2 testis. These included a set of GDNF-dependent genes, such as Etv5, Bcl6b, Lhx1, Brachyury, Id4, and Pou3f1, and GDNF-independent genes, such as FoxO1, Oct4, and Zbtb16. Impairment of the nuclear localization of FoxO1 may be in part responsible for the reduced expression of Ret, Lhx1, and Sall4 in Glis3KO2 testis. Our study identifies Glis3 as a novel and critical regulator of early stages of spermatogenesis. Thy1+ cells were isolated from 3 WT and 3 Glis3KO2 testis at postnatal day 4, and total RNAs were purified from them. Then the samples were applied to Agilent mouse genome chip.
2016-07-01 | E-GEOD-70195 | biostudies-arrayexpress
Project description:Renal repair after injury is dependent on clonal expansion of proliferation competent cells. In the human kidney, the expression of CD133+ characterizes a population of resident scattered cells with resistance to damage and ability to proliferate. However, the biological function of the CD133 molecule is unknown. We found by RNA sequencing that cells undergoing cisplatin damage lost the CD133 signature and acquired metanephric mesenchymal and regenerative genes such as SNAIL1, KLF4, SOX9 and WNT3. CD133 was reacquired in the recovery phase. Lack of CD133 was specifically correlated with deregulation of the Wnt signalling and E-cadherin pathway and, functionally, limited cell proliferation after injury. By immunoprecipitation, CD133 appeared to form a complex with E-cadherin and β-catenin. In parallel, CD133-Kd cells showed lower β-catenin levels in basal condition and after Wnt pathway activation and reduced TCF/LEF promoter activation in respect to CD133+ cells. Finally, the lack of CD133 impaired generation of nephrospheres while favored senescence. These data indicate that CD133 may act as a permissive factor for beta-catenin signalling, preventing its degradation in the cytoplasm. Therefore, CD133 itself appears to play a functional role in renal tubular repair trough maintenance of proliferative response and control of senescence.
2018-03-07 | GSE107273 | GEO
Project description:Loss of transcription factor GLIS3 function in humans and mice leads to the development of neonatal polycystic kidney disease (PKD). To investigate how loss of GLIS3 function in kidney affects postnatal kidney development and PKD, we analyzed the gene expression profiles of kidneys from WT and Glis3-null mice at P7, P14, and P28 by RNA-Seq analysis using Glis3 global KO model Glis3-mCherry.
2024-12-18 | GSE240532 | GEO
Project description:We show that Glis3 is expressed in gonocytes, SSCs and SPCs, but not in differentiated spermatogonia or subsequent stages of spermatogenesis nor in Sertoli or Leydig cells. We further demonstrate that Glis3-deficiency causes a severe impairment in spermatogenesis in mice. Although the number of gonocytes was slightly diminished in Glis3KO testis, the number undifferentiated, PLZF+ spermatogonia was dramatically reduced leading to a virtual block in the progression of spermatogenesis. Gene expression profiling showed that the expression of a number of genes associated with self-renewal and differentiation of spermatogonial cells was significantly decreased in 1-week-old Glis3KO2 testis. These included a set of GDNF-dependent genes, such as Etv5, Bcl6b, Lhx1, Brachyury, Id4, and Pou3f1, and GDNF-independent genes, such as FoxO1, Oct4, and Zbtb16. Impairment of the nuclear localization of FoxO1 may be in part responsible for the reduced expression of Ret, Lhx1, and Sall4 in Glis3KO2 testis. Our study identifies Glis3 as a novel and critical regulator of early stages of spermatogenesis. Testis total RNAs were purified from 4 WT and 4 Glis3KO2 at 1 week old age, and 3WT and 3 Glis3KO2 at 3 week-old age. Then the samples were applied to Agilent mouse genome chip.
2016-07-01 | E-GEOD-70194 | biostudies-arrayexpress
Project description:We show that Glis3 is expressed in gonocytes, SSCs and SPCs, but not in differentiated spermatogonia or subsequent stages of spermatogenesis nor in Sertoli or Leydig cells. We further demonstrate that Glis3-deficiency causes a severe impairment in spermatogenesis in mice. Although the number of gonocytes was slightly diminished in Glis3KO testis, the number undifferentiated, PLZF+ spermatogonia was dramatically reduced leading to a virtual block in the progression of spermatogenesis. Gene expression profiling showed that the expression of a number of genes associated with self-renewal and differentiation of spermatogonial cells was significantly decreased in 1-week-old Glis3KO2 testis. These included a set of GDNF-dependent genes, such as Etv5, Bcl6b, Lhx1, Brachyury, Id4, and Pou3f1, and GDNF-independent genes, such as FoxO1, Oct4, and Zbtb16. Impairment of the nuclear localization of FoxO1 may be in part responsible for the reduced expression of Ret, Lhx1, and Sall4 in Glis3KO2 testis. Our study identifies Glis3 as a novel and critical regulator of early stages of spermatogenesis.
2016-07-01 | GSE70195 | GEO
Project description:We show that Glis3 is expressed in gonocytes, SSCs and SPCs, but not in differentiated spermatogonia or subsequent stages of spermatogenesis nor in Sertoli or Leydig cells. We further demonstrate that Glis3-deficiency causes a severe impairment in spermatogenesis in mice. Although the number of gonocytes was slightly diminished in Glis3KO testis, the number undifferentiated, PLZF+ spermatogonia was dramatically reduced leading to a virtual block in the progression of spermatogenesis. Gene expression profiling showed that the expression of a number of genes associated with self-renewal and differentiation of spermatogonial cells was significantly decreased in 1-week-old Glis3KO2 testis. These included a set of GDNF-dependent genes, such as Etv5, Bcl6b, Lhx1, Brachyury, Id4, and Pou3f1, and GDNF-independent genes, such as FoxO1, Oct4, and Zbtb16. Impairment of the nuclear localization of FoxO1 may be in part responsible for the reduced expression of Ret, Lhx1, and Sall4 in Glis3KO2 testis. Our study identifies Glis3 as a novel and critical regulator of early stages of spermatogenesis.
2016-07-01 | GSE70194 | GEO