Simulation of proliferation and differentiation of cells in a stem-cell niche

2008 ◽  
Vol 387 (24) ◽  
pp. 6126-6136 ◽  
Author(s):  
Vladimir P. Zhdanov
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Proliferation And Differentiation ◽  
Cell Niche

Mir-886-3p Contributes to the Regulation of the hematopoietic microenvironment by down-Regulating SDF-1α (CXCL12).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 561-561
Author(s):  
Manoj M Pillai ◽  
Xiaodong Yang ◽  
Mineo Iwata ◽  
Lynne Bemis ◽  
Beverly Torok-Storb
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Stromal Cells ◽  
Stem Cell Niche ◽  
Expression Profiles ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Proliferation And Differentiation ◽  
Cell Niche ◽  
Angiopoietin 1

Abstract Abstract 561 Two functionally distinct stromal cell lines were isolated from a primary long term culture (LTC) established from aspirated human marrow. Designated HS5 and HS27a, the lines were immortalized and extensively characterized including expression profiles for both messenger (mRNA) and micro-RNA (miRNA, a recently described class of small non-coding RNAs that regulate gene expression by binding to target mRNAs to prevent their translation). HS5 was found to secrete growth factors that stimulate proliferation and differentiation of hematopoietic progenitors (G-CSF, IL-6, IL-1α and IL1β), whereas HS27a expresses activities associated with the stem cell niche (SDF-1αa, angiopoietin-1 etc). In keeping with this HS5 conditioned media stimulated proliferation and differentiation of isolated CD34+ cells whereas HS27a supported CD34+ cells in an undifferentiated state. When cultured together to better mimic in vivo cell-cell interactions, the gene expression of HS27a and HS5 combined differed from the expected sum of the two parts, exemplified by the 5-fold down regulation of SDF-1α. Comparisons of miRNA expression profiles of HS5 and HS27a determined that mir-886-3p, (previously described by deep sequencing of small RNA libraries) was expressed > 40 fold in HS5 compared to HS27a, this was then confirmed by quantitative RT-PCR. Given the abundance of mir-886-3p and the possibility that it could be secreted by HS5 and taken up by cells in contact with HS5, we tested its effect on gene expression in HS27a. Transcript levels of genes associated with the stem cell niche (Jagged1, BMP4, Angiopoietin-1, SDF-1α, VCAM-1 and N-Cadherin) were determined by quantitative RT-PCR after direct transfection of mir-886-3p precursors into HS27a cells and compared to appropriate controls. Results show SDF-1α mRNA expression was down-regulated by as much as 8 fold 3 days after transfection. Levels of secreted SDF-1α in culture media, as determined by ELISA, were also decreased. Since SDF-1α is a chemokine known to be critical for the homing of hematopoietic stem and progenitor cells to their niche, the functional significance of the SDF-1α down-regulation by mir-886-3p was confirmed by decreased chemotaxis of T-lymphocytic cells (Jurkat) following miRNA transfection of stromal cells. To determine if mir-886-3p directly effects the SDF-1α transcript, the 1.5 kbp 3'untranslated region (UTR) of SDF-1α gene was cloned downstream of the luciferase gene, and co-transfected with mir-886-3p into HS27a cells. Results showed the luciferase activity was down-regulated greater than 50% in the presence of mir-886-3p, suggesting a direct effect on the SDF-1 α transcript. Given the concern over the relevance of immortalized cell lines we investigated Mir-886-3p expression in primary marrow stromal cells at early passage sorted on the basis of +/- expression of CD146. (CD146 or MCAM has been reported to define a population that supports the hematopoietic stem/ precursor cell niche and is expressed by HS27a and not HS5 cells). Results indicated that the CD146+ stromal cells had significantly lower expression of mir-886-3p when compared to CD146- cells. In summary, these data suggest a role for miRNA in modulating the expression of gene products that are associated with the hematopoietic stem cell niche. Disclosures: No relevant conflicts of interest to declare.

scholarly journals mRNA-Expression of ERα, ERβ, and PR in Clonal Stem Cell Cultures Obtained from Human Endometrial Biopsies

2011 ◽  
Vol 11 ◽  
pp. 1762-1769 ◽  
Author(s):  
A. N. Schüring ◽  
J. Braun ◽  
S. Wüllner ◽  
L. Kiesel ◽  
M. Götte
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Adult Stem Cells ◽  
Direct Stimulation ◽  
Regenerative Capacity ◽  
Endometrial Stem Cells ◽  
Proliferation And Differentiation ◽  
Clonal Cultures ◽  
Cell Niche

Background. Proliferation and differentiation of the endometrium are regulated by estrogen and progesterone. The enormous regenerative capacity of the endometrium is thought to be based on the activity of adult stem cells. However, information on endocrine regulatory mechanisms in human endometrial stem cells is scarce. In the present study, we investigated the expression of ERα, ERβ, and PR in clonal cultures of human endometrial stem cells derived from transcervical biopsies.Methods. Endometrial tissue of 11 patients was obtained by transcervical biopsy. Stromal cell suspensions were plated at clonal density and incubated for 15 days. Expression of ERα, ERβand PR was determined by qPCR prior to and after one cloning round, and normalized to 18 S rRNA expression.Results. Expression of ERαand ERβwas downregulated by 64% and 89%, respectively ( and ). In contrast, PR was not significantly downregulated, due to a more heterogenous expression pattern.Conclusions. Culture of human endometrial stroma cells results in a downregulation of ERαand ERβ, while expression of PR remained unchanged in our patient collective. These results support the hypothesis that stem cells may not be subject to direct stimulation by sex steroids, but rather by paracrine mechanisms within the stem cell niche.

scholarly journals The transcription factor CLAMP is required for neurogenesis in Drosophila melanogaster

2020 ◽  
Author(s):  
Maria A. Tsiarli ◽  
Ashley M. Conard ◽  
Lucy Xu ◽  
Erica Nguyen ◽  
Erica N. Larschan
Keyword(s):  
Transcription Factor ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Target Genes ◽  
Transcriptional Program ◽  
Glial Development ◽  
Proliferation And Differentiation ◽  
Transcriptional Changes ◽  
Cell Niche ◽  
External Signals

AbstractNeural stem cell (NSC) differentiation is controlled by cell-intrinsic and external signals from the stem cell niche including niche surface glia (SG). However, the mechanisms by which transcription factors drive NSC differentiation within the niche remain largely unknown. Here, we show that the transcription factor, Chromatin-linked adaptor for MSL proteins (CLAMP) is required for NSC differentiation. CLAMP promotes transcription of genes involved in stemness, proliferation, and glial development and represses transcription of genes involved in neurogenesis and niche survival. Consistent with transcriptional changes, CLAMP promotes NSC proliferation and SG production. Furthermore, glial-specific knock-down of clamp causes similar phenotypes to clamp null mutants. CLAMP motifs are present at many target genes including the glial-determining gene, glial cells missing, and Notch, a key regulator of neurogenesis. Collectively, our results suggest that CLAMP regulates a transcriptional program which drives NSC proliferation and differentiation via cell-intrinsic and niche-dependent mechanisms that involve niche glia.

scholarly journals PDGFRα+ pericryptal stromal cells are the critical source of Wnts and RSPO3 for murine intestinal stem cells in vivo

2018 ◽  
Vol 115 (14) ◽  
pp. E3173-E3181 ◽  
Author(s):  
Gediminas Greicius ◽  
Zahra Kabiri ◽  
Kristmundur Sigmundsson ◽  
Chao Liang ◽  
Ralph Bunte ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Ex Vivo ◽  
Paneth Cell ◽  
Intestinal Stem Cells ◽  
Intestinal Stem Cell ◽  
Intestinal Crypt ◽  
Proliferation And Differentiation ◽  
Cell Niche

Wnts and R-spondins (RSPOs) support intestinal homeostasis by regulating crypt cell proliferation and differentiation. Ex vivo, Wnts secreted by Paneth cells in organoids can regulate the proliferation and differentiation of Lgr5-expressing intestinal stem cells. However, in vivo, Paneth cell and indeed all epithelial Wnt production is completely dispensable, and the cellular source of Wnts and RSPOs that maintain the intestinal stem-cell niche is not known. Here we investigated both the source and the functional role of stromal Wnts and RSPO3 in regulation of intestinal homeostasis. RSPO3 is highly expressed in pericryptal myofibroblasts in the lamina propria and is several orders of magnitude more potent than RSPO1 in stimulating both Wnt/β-catenin signaling and organoid growth. Stromal Rspo3 ablation ex vivo resulted in markedly decreased organoid growth that was rescued by exogenous RSPO3 protein. Pdgf receptor alpha (PdgfRα) is known to be expressed in pericryptal myofibroblasts. We therefore evaluated if PdgfRα identified the key stromal niche cells. In vivo, Porcn excision in PdgfRα+ cells blocked intestinal crypt formation, demonstrating that Wnt production in the stroma is both necessary and sufficient to support the intestinal stem-cell niche. Mice with Rspo3 excision in the PdgfRα+ cells had decreased intestinal crypt Wnt/β-catenin signaling and Paneth cell differentiation and were hypersensitive when stressed with dextran sodium sulfate. The data support a model of the intestinal stem-cell niche regulated by both Wnts and RSPO3 supplied predominantly by stromal pericryptal myofibroblasts marked by PdgfRα.

Tissue Stem Cells and Stem Cell Niche of the Human Vocal Fold

2020 ◽  
Vol 71 (2) ◽  
pp. 211-213
Author(s):  
K. Sato ◽  
S. Chitose ◽  
K. Sato ◽  
F. Sato ◽  
T. Kurita ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Vocal Fold ◽  
Cell Niche
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