scholarly journals Maintenance of Adult Stem Cells: Role of the Stem Cell Niche

2011 ◽  
pp. 35-55 ◽  
Author(s):  
Yoshiko Matsumoto ◽  
Hiroko Iwasaki ◽  
Toshio Suda
2011 ◽  
Vol 11 ◽  
pp. 1762-1769 ◽  
Author(s):  
A. N. Schüring ◽  
J. Braun ◽  
S. Wüllner ◽  
L. Kiesel ◽  
M. Götte

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.


2017 ◽  
Author(s):  
Wei Dai ◽  
Amy Peterson ◽  
Thomas Kenney ◽  
Denise J. Montell

AbstractAdult stem cells commonly give rise to transit-amplifying progenitors, whose progeny differentiate into distinct cell types. Signals within the stem cell niche maintain the undifferentiated state. However it is unclear whether or how niche signals might also coordinate fate decisions within the progenitor pool. Here we use quantitative microscopy to elucidate distinct roles for Wnt, Hedgehog (Hh), and Notch signalling in progenitor development in the Drosophila ovary. Follicle stem cells (FSCs) self-renew and produce precursors whose progeny adopt distinct polar, stalk, and main body cell fates. We show that a steep gradient of Wnt signalling maintains a multipotent state in proximally located progenitor cells by inhibiting expression of the cell fate determinant Eyes Absent (Eya). A shallower gradient of Hh signalling controls the proliferation to differentiation transition. The combination of Notch and Wnt signalling specifies polar cells. These findings reveal a mechanism by which multiple niche signals coordinate cell fate diversification of progenitor cells.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 858-858
Author(s):  
Hiroki Yoshihara ◽  
Fumio Arai ◽  
Kentaro Hosokawa ◽  
Takao Takahashi ◽  
Hiroshi Miyazaki ◽  
...  

Abstract Hematopoietic stem cells (HSCs) have the ability to self-renew and to differentiate to produce multi-lineage blood cells throughout the lifetime of individuals. Maintenance of these stem cell activities depends on the balance of intrinsic and extrinsic factors. The factors which regulate HSCs are provided by a microenvironment called stem cell niche, and interactions between HSCs and stem cell niche is critical for the maintenance of stem cell activities. Recently, it has been reported that HSCs exist frequently aside of the trabecular bone surface in bone marrow (BM). We have previously reported that side-population (SP) in HSC fraction is in the G0 phase and anti-apoptotic stem cells, and contacts osteoblasts. (Arai et al., Cell 2004). To further investigate the regulation of quiescence, cell adhesion, and survival of HSCs, we tried to clone the quiescent HSCs specific molecules by microarray analysis of c-Kit+Sca-1+Lin− (KSL)-SP vs. non-SP cells. We identified that Mpl, thrombopoietin (Tpo) receptor, was highly expressed in SP cells compared to non-SP cells. Tpo/Mpl signal is known as a physiological regulator of megakaryopoiesis, but the role of Tpo/Mpl signal in the maintenance of HSCs remains elusive. In this study, we investigated the role of Tpo/Mpl signal on the regulation of HSCs in the niche. The frequency of Mpl+ cells in KSL, KSL-SP, and KSL-non SP cells were 50.4 %, 88.9 %, and 44.7 %, respectively. In addition, Tpo was expressed in osteoblastic cells in BM. Immunohistochemical staining of BM showed that Mpl+ HSCs adhered to the bone surface and bone-lining osteoblastic cells produced Tpo. These data suggest that Tpo/Mpl signal contributes to the HSCs-niche interaction. BM transplantation (BMT) assay demonstrated that Mpl+KSL cells showed high long-term reconstitution (LTR)-activity, whereas Mpl−KSL cells did not, suggesting that LTR-HSCs were enriched in Mpl+ fraction. To investigate the function of Tpo/Mpl signal in HSCs, we performed CAFC assay and LTC-IC assay in the presence of anti-Mpl neutralizing antibody (AMM2). Inhibition of Tpo/Mpl signal reduced cobblestone formation and reduced LTC-IC formation. These data suggest that Tpo/Mpl signal maintained immature phenotypes of HSCs in vitro. It was reported that Mpl deficient mice showed the defect of stem cell function. For rapid and transient inhibition of Mpl signaling in vivo, we administrated AMM2 into the adult mice. AMM2 did not affect the frequency of non-SP fraction, but transiently decreased frequency of SP in KSL after 6 days of injection. Moreover, the combination of AMM2 and 5-FU capacitated BMT without irradiation. In contrast, injection of Tpo increased KSL-SP cells. To understand the mechanism of Tpo/Mpl signal, we cultured Mpl+KSL cells in the presence of SCF and/or Tpo, and analyzed the gene expression. We found that Tpo treatment up-regulate β1-integrin and p57, but not p21, p27 or p18. As the up-regulation of p57 is essential for TGF-β induced cell cycle arrest in hematopoiesis, Tpo/Mpl signal may also be related to cell cycle arrest. Altogether, these data suggest that Tpo/Mpl signal regulates HSCs-niche interaction and enhanced the quiescence of HSCs.


Author(s):  
Ilaria Tortorella ◽  
Chiara Argentati ◽  
Carla Emiliani ◽  
Sabata Martino ◽  
Francesco Morena

AbstractOrganoids are a novel three-dimensional stem cells’ culture system that allows the in vitro recapitulation of organs/tissues structure complexity. Pluripotent and adult stem cells are included in a peculiar microenvironment consisting of a supporting structure (an extracellular matrix (ECM)-like component) and a cocktail of soluble bioactive molecules that, together, mimic the stem cell niche organization. It is noteworthy that the balance of all microenvironmental components is the most critical step for obtaining the successful development of an accurate organoid instead of an organoid with heterogeneous morphology, size, and cellular composition. Within this system, mechanical forces exerted on stem cells are collected by cellular proteins and transduced via mechanosensing—mechanotransduction mechanisms in biochemical signaling that dictate the stem cell specification process toward the formation of organoids. This review discusses the role of the environment in organoids formation and focuses on the effect of physical components on the developmental system. The work starts with a biological description of organoids and continues with the relevance of physical forces in the organoid environment formation. In this context, the methods used to generate organoids and some relevant published reports are discussed as examples showing the key role of mechanosensing–mechanotransduction mechanisms in stem cell-derived organoids.


2021 ◽  
Vol 23 (12) ◽  
Author(s):  
Sonja Heibl ◽  
Reinhard Stauder ◽  
Michael Pfeilstöcker

Abstract Purpose of Review To review available data on the relationship of MDS and aging and to address the question if biological changes of (premature) aging are a prerequisite for the development of MDS. Recent Findings Whereas the association of MDS with advanced age and some common biologic features of aging and MDS are well established, additional evidence for both, especially on the role of stem cells, the stem cell niche, and inflammation, has been recently described. Summary Biologically, many but not all drivers of aging also play a role in the development and propagation of MDS and vice versa. As a consequence, aging contributes to the development of MDS which can be seen as an interplay of clonal disease and normal and premature aging. The impact of aging may be different in specific MDS subtypes and risk groups.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2208-2208
Author(s):  
Young-Ju Kang ◽  
Eek-hoon Jho ◽  
Hanjun Kim ◽  
Gyeongsin Park ◽  
Jae-Seung Shim ◽  
...  

Abstract With contrasting results recently reported on the effects of b-catenin on hematopoietic stem cells (HSCs), the precise role of Wnt on HSC regulation remains in question. Here, we show that Wnt-b-catenin signaling triggers distinct biological effects on HSCs depending on the target of activation within the hematopoietic microenvironment. Retroviral transduction of a stable form of b-catenin into HSCs caused a loss of competitive repopulating units (CRUs) in a limiting-dilution assay, whereas stabilized b-catenin in stromal cells CRU frequencies of co-cultured HSCs with higher preservation of undifferentiated state and caused enhanced levels of reconstitution in a manner dependent on direct contact between HSC and stroma. The enhancing effect of b-catenin stabilized stroma on HSC was also observed for human HSCs exhibiting higher frequencies of lympho-myeloid repopulating cells after transplantation into NOD/SCID mice. Interestingly, gene expression patterns of Wnt signaling molecules revealed compartmentalization in a manner that canonical Wnt ligands were preferentially expressed in the hematopoietic cells while molecules for reception of the signal such as Frizzled receptors or their co-receptors are preferentially expressed in stromal component, suggesting the role of stromal component as a target of Wnt signals in the niche. Furthermore, b-catenin accumulated selectively in the endosteal stroma of the trabecule region in “stressed” marrows, but not in “steady-state” marrows. Taken together, these results suggest stroma-mediated Wnt signals may function as microenvironmental cues for HSC self-renewal in the stem cell niche.


2020 ◽  
Vol 71 (2) ◽  
pp. 211-213
Author(s):  
K. Sato ◽  
S. Chitose ◽  
K. Sato ◽  
F. Sato ◽  
T. Kurita ◽  
...  

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