scholarly journals PpRPK2 modulates auxin homeostasis and transport to specify stem cell identity and plant shape in the moss Physcomitrella

2021 ◽  
Author(s):  
Zoe Nemec Venza ◽  
Connor Madden ◽  
Amy Stewart ◽  
Wei Liu ◽  
Ondrej Novak ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Function ◽  
Cell Activity ◽  
Fundamental Property ◽  
Land Plant ◽  
Cell Identity ◽  
Auxin Homeostasis ◽  
Plant Stem ◽  
Plant Form ◽  
Hormone Homeostasis

Plant shape is determined by the activity of stem cells in the growing tips, and evolutionary changes in shape are linked to changes in stem cell function. The CLAVATA pathway is a key regulator of stem cell function in the multicellular shoot tips of Arabidopsis, acting via the WUSCHEL transcription factor to modulate hormone homeostasis. Broad scale evolutionary comparisons have shown that CLAVATA is a conserved regulator of land plant stem cell function, but CLAVATA acts independently of WUSCHEL-like (WOX) proteins in bryophytes, raising questions about the evolution of stem cell function and the role of the CLAVATA pathway. Here we show that the moss (Physcomitrella) CLAVATA pathway affects stem cell activity and overall plant shape by modulating hormone homeostasis. CLAVATA pathway components are expressed in the tip cells of filamentous tissues, regulating cell identity, filament branching patterns and plant spread. The PpRPK2 receptor-like kinase plays the major role and is expressed more strongly than other receptor-encoding genes. Pprpk2 mutants have abnormal responses to cytokinin, and auxin transport inhibition and show reduced PIN auxin transporter expression. We propose a model whereby PpRPK2 modulates PIN activity to determine stem cell identity and overall plant form in Physcomitrella. Our data indicate that CLAVATA-mediated auxin homeostasis is a fundamental property of plant stem cell function likely exhibited by the last shared common ancestor of land plants.

scholarly journals Multiple Roles for Cholinergic Signaling from the Perspective of Stem Cell Function

2021 ◽  
Vol 22 (2) ◽  
pp. 666
Author(s):  
Toshio Takahashi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Function ◽  
Cell Activity ◽  
Embryonic Stem ◽  
Cholinergic Neurons ◽  
Cell Types ◽  
Proliferative Potential ◽  
True Nature ◽  
Cholinergic Signaling

Stem cells have extensive proliferative potential and the ability to differentiate into one or more mature cell types. The mechanisms by which stem cells accomplish self-renewal provide fundamental insight into the origin and design of multicellular organisms. These pathways allow the repair of damage and extend organismal life beyond that of component cells, and they probably preceded the evolution of complex metazoans. Understanding the true nature of stem cells can only come from discovering how they are regulated. The concept that stem cells are controlled by particular microenvironments, also known as niches, has been widely accepted. Technical advances now allow characterization of the zones that maintain and control stem cell activity in several organs, including the brain, skin, and gut. Cholinergic neurons release acetylcholine (ACh) that mediates chemical transmission via ACh receptors such as nicotinic and muscarinic receptors. Although the cholinergic system is composed of organized nerve cells, the system is also involved in mammalian non-neuronal cells, including stem cells, embryonic stem cells, epithelial cells, and endothelial cells. Thus, cholinergic signaling plays a pivotal role in controlling their behaviors. Studies regarding this signal are beginning to unify our understanding of stem cell regulation at the cellular and molecular levels, and they are expected to advance efforts to control stem cells therapeutically. The present article reviews recent findings about cholinergic signaling that is essential to control stem cell function in a cholinergic niche.

scholarly journals Set1 Targets Genes with Essential Identity and Tumor-Suppressing Functions in Planarian Stem Cells

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1182
Author(s):  
Prince Verma ◽  
Court K. M. Waterbury ◽  
Elizabeth M. Duncan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mammalian Cells ◽  
Cell Function ◽  
Genotoxic Stress ◽  
Specific Gene ◽  
Cell Identity ◽  
Chromatin Signature ◽  
Lysine Methyltransferase

Tumor suppressor genes (TSGs) are essential for normal cellular function in multicellular organisms, but many TSGs and tumor-suppressing mechanisms remain unknown. Planarian flatworms exhibit particularly robust tumor suppression, yet the specific mechanisms underlying this trait remain unclear. Here, we analyze histone H3 lysine 4 trimethylation (H3K4me3) signal across the planarian genome to determine if the broad H3K4me3 chromatin signature that marks essential cell identity genes and TSGs in mammalian cells is conserved in this valuable model of in vivo stem cell function. We find that this signature is indeed conserved on the planarian genome and that the lysine methyltransferase Set1 is largely responsible for creating it at both cell identity and putative TSG loci. In addition, we show that depletion of set1 in planarians induces stem cell phenotypes that suggest loss of TSG function, including hyperproliferation and an abnormal DNA damage response (DDR). Importantly, this work establishes that Set1 targets specific gene loci in planarian stem cells and marks them with a conserved chromatin signature. Moreover, our data strongly suggest that Set1 activity at these genes has important functional consequences both during normal homeostasis and in response to genotoxic stress.

scholarly journals Nfatc1’s Role in Mammary Epithelial Morphogenesis and Basal Stem/progenitor Cell Self-renewal

2021 ◽  
Author(s):  
Melissa McNeil ◽  
Yingying Han ◽  
Peng Sun ◽  
Kazuhide Watanabe ◽  
Jun Jiang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mammary Gland ◽  
Progenitor Cell ◽  
Cell Function ◽  
Cell Activity ◽  
Basal Layer ◽  
Mammary Epithelial ◽  
Epithelial Morphogenesis ◽  
Small Subset ◽  
Self Renewal

AbstractMammary gland is an outstanding system to study the regulatory mechanisms governing adult epithelial stem cell activity. Stem cells in the basal layer of the mammary gland fuel the morphogenesis and regeneration of a complex epithelial network during development and upon transplantation. The self-renewal of basal stem/progenitor cells is subjected to regulation by both cell-intrinsic and extrinsic mechanisms. Nfatc1 is a transcription factor that regulates breast tumorigenesis and metastasis, but its role in mammary epithelial development and stem cell function has not been investigated. Here we show that Nfatc1 is expressed in a small subset of mammary basal epithelial cells and its epithelial-specific deletion results in mild defects in side branching and basal-luminal cell balance. Moreover, Nfatc1-deficient basal cells exhibit reduced colony forming ability in vitro and somewhat compromised regenerative potential upon transplantation. Thus, our study provides evidence for a detectable yet non-essential role of Nfatc1 in mammary epithelial morphogenesis and basal stem/progenitor cell self-renewal.

Normal Hematopoietic Stem Cell Functioning in p21−/− Mice.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1701-1701
Author(s):  
Leonie M. Kamminga ◽  
Kyrjon van Pelt ◽  
Bert Dontje ◽  
Gerald de Haan
Keyword(s):  
Stem Cell ◽  
Kinase Inhibitors ◽  
Cell Function ◽  
Cell Activity ◽  
Homozygous Deletion ◽  
Hematopoietic Stem ◽  
Mixed Genetic Background ◽  
Senescent Phenotype

Abstract Recently, several studies have suggested that the family of cyclin-dependent kinase inhibitors plays a crucial role in regulating hematopoietic stem and progenitor pool size. However, due to a lack of appropriate transplantation models, competitive repopulation assays have not been performed. In the present study we have backcrossed a p21 null allele from mice with a mixed genetic background to inbred C57BL/6 mice. As expected, mouse embryonic fibroblasts (MEFs) derived from B6p21−/− mice failed to undergo senescence, whereas B6p21+/+ MEFs show a normal senescent phenotype. Moreover, B6p21−/− CFU-GM were more resistant to radiation compared to B6p21+/+. In contrast, homozygous deletion of the p21 allele did not affect the percentage of Lin− Sca-1+ c-kit+ cells in S-phase when measured by 7-AAD staining, and did not result in any alterations of in vitro cobblestone area forming cell activity. In a competitive repopulating assay different ratios of Ly5.2 BM cells from B6p21−/− or B6p21+/+ littermates were competed with 2 x 106 Ly5.1 B6 BM cells. Assuming similar repopulating capacity of both cell populations, expected chimerism was calculated. Surprisingly, observed and expected chimerism were identical, strongly suggesting that B6p21−/− stem cells had completely normal competitive repopulating activity for up to 1 year after transplant. Our data argue against an important role of p21 in maintaining stem cell function during steady-state hematopoiesis.

scholarly journals Investigation of Stem Cell Aging Throughout the Lifetime and Therapeutic Opportunities

2020 ◽  
Author(s):  
Sarah Karimi ◽  
Setareh Raoufi ◽  
Zohreh Bagher
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Aging Process ◽  
Cell Function ◽  
Cell Activity ◽  
The Body ◽  
Natural Phenomenon ◽  
Cell Aging ◽  
Molecular Pathways ◽  
Stem Cell Aging

Introduction: Aging is a natural phenomenon that is caused by changes in the cells of the body. Theoretically, aging starts from birth and lasts throughout life. These changes affect the function of the cells. Also, in old tissues, the capacity for homeostasis and tissue repair is decline due to destructive changes in specific tissue stem cells, niche of stem cells and systemic factors that regulate stem cell activity. Understanding molecular pathways that disrupt stem cell function during aging is crucial for the development of new treatments for aging-associated diseases. In this article, the symptoms of stem cell aging and the key molecular pathways that are commonly used for the aging of stem cells were discussed. We will consider experimental evidence for all of the mechanisms and evaluate the way that can slow down or even stop the aging process. Finally, we will look at the aging process of three types of stem cells.

scholarly journals Molecular regulation of plant stem cell function

2020 ◽  
Vol 50 (2) ◽  
pp. 187-195
Author(s):  
XiaoNing HAN ◽  
HuiHong GUO ◽  
JingYi MA
Keyword(s):  
Stem Cell ◽  
Cell Function ◽  
Molecular Regulation ◽  
Plant Stem

Azacytidine Compromises NK-Cell Activity in AML and MDS Patients Undergoing MRD-Based Pre-Emptive Treatment After Allogeneic Stem Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4122-4122
Author(s):  
Katja Sockel ◽  
Claudia Schönefeldt ◽  
Sieghart Sopper ◽  
Martin Wermke ◽  
Marc Schmitz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Function ◽  
Nk Cell ◽  
Cell Activity ◽  
Nk Cell Activity ◽  
Activating Receptors

Abstract Abstract 4122 The hypomethylating agent azacytidine (AZA) represents the standard treatment for many high-risk MDS and AML patients. While the clinical efficacy has been confirmed in several studies, the precise molecular mechanism of action has not been fully understood yet. Human NK-cells play an important role in the regulation of immune responses against malignant cells. Their function is controlled by a complex interplay of activating and inhibitory receptors - some of them being regulated by methylation of the respective genes. We, therefore explored, whether AZA modulates in vitro NK-cell function as well as in vivo during minimal-residual disease (MRD)-guided treatment of imminent relapse in MDS and AML patients treated within the prospective RELAZA trial (NCT00422890). Methods: After purifying NK-cells of healthy donors by MACS (magnetic cell sorting), NK-cells were exposed in vitro to different concentrations of AZA (100nM, 1μM, 3μM) with or without IL-2. In parallel, the NK-cell phenotype of patients (n=12) with AML or MDS, undergoing MRD-guided treatment with AZA after stem cell transplantation was monitored by FACS from peripheral blood samples on day 1, 5 and 7 of the first and second AZA cycle. All patients were still in complete haematological remission at the time of therapy. Results: In vitro, we observed a significant reduction (3,1% to 1,8% p=0.028) of the immature and cytokine-regulating CD56bright NK-cell subpopulation with increasing concentrations of AZA. There was a trend towards a reduced expression of the death-ligand TRAIL, the activating receptors NKG2D and NKp46 and for an increased expression of the inhibitory KIR CD158b1/b2, whereas we could not detect any changes in the expression of FAS-L, Perforin, Granzyme B, NKp30, NKp44, CD69, CD57, DNAM-1, CD16, and NKG2A-CD94. Confirmatory, we observed a significant decrease in the expression of TRAIL (p=0.003), NKG2D (p=0.03) and NKp46 (p=0.006) during AZA treatment in-vivo. Interestingly, these changes appeared to be reversible. The observed reduction of NK-cell activating receptors and TRAIL during AZA treatment correlated with a reduction or stable course of MRD in all analyzed patients. Conclusion: In summary these data suggest that the clinical effects of AZA are not mediated by enhancing NK-cell activity. In fact, the drug may have inhibitory effects on NK-cell function which should be considered when applying AZA in the post-transplant setting. Disclosures: Platzbecker: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Control of plant stem cell function by conserved interacting transcriptional regulators

Nature ◽  
2014 ◽  
Vol 517 (7534) ◽  
pp. 377-380 ◽  
Author(s):  
Yun Zhou ◽  
Xing Liu ◽  
Eric M. Engstrom ◽  
Zachary L. Nimchuk ◽  
Jose L. Pruneda-Paz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Function ◽  
Transcriptional Regulators ◽  
Plant Stem

scholarly journals The intrinsic chaperone network of Arabidopsis stem cells confers protection against proteotoxic stress

2021 ◽  
Author(s):  
Ernesto Llamas ◽  
Salvador Torres-Montilla ◽  
Hyun Ju Lee ◽  
María Victoria Barja ◽  
Elena Schlimgen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Protein Aggregation ◽  
Cell Function ◽  
Proteasome Inhibition ◽  
Stem Cell Maintenance ◽  
Proteotoxic Stress ◽  
Differentiated Cells ◽  
Plant Stem ◽  
Chaperone Network

AbstractThe biological purpose of plant stem cells is to maintain themselves while providing new pools of differentiated cells that form organs and rejuvenate or replace damaged tissues1-3. Protein homeostasis, or proteostasis, is required for cell function and viability4-7. However, the link between proteostasis and plant stem cell identity remains unknown. In contrast to their differentiated counterparts, we find that root stem cells can prevent the accumulation of aggregated proteins even under proteotoxic stress conditions such as heat stress or proteasome inhibition. Notably, root stem cells exhibit enhanced expression of distinct chaperones that maintain proteome integrity. Particularly, intrinsic high levels of the TRiC/CCT chaperonin determine stem cell maintenance and their remarkable ability to suppress protein aggregation. Overexpression of CCT8, a key activator of TRiC/CCT assembly8, is sufficient to ameliorate protein aggregation in differentiated cells and confer resistance to proteotoxic stress in plants. Taken together, our results indicate that enhanced proteostasis mechanisms in stem cells could be an important requirement for plants to persist under extreme environmental conditions and reach extreme long ages. Thus, proteostasis of stem cells could provide insights to design and breed plants tolerant to environmental challenges caused by the climate change.

scholarly journals Loss of tyrosine kinase receptor Ephb2 impairs proliferation and stem cell activity of spermatogonia in culture†

2019 ◽  
Vol 102 (4) ◽  
pp. 950-962
Author(s):  
Thierry N’Tumba-Byn ◽  
Makiko Yamada ◽  
Marco Seandel
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Function ◽  
Cultured Cells ◽  
Cell Activity ◽  
Mapk Signaling ◽  
Tyrosine Kinase Receptor ◽  
Wild Type ◽  
Stem Cell Activity

Abstract Germline stem and progenitor cells can be extracted from the adult mouse testis and maintained long-term in vitro. Yet, the optimal culture conditions for preserving stem cell activity are unknown. Recently, multiple members of the Eph receptor family were detected in murine spermatogonia, but their roles remain obscure. One such gene, Ephb2, is crucial for maintenance of somatic stem cells and was previously found enriched at the level of mRNA in murine spermatogonia. We detected Ephb2 mRNA and protein in primary adult spermatogonial cultures and hypothesized that Ephb2 plays a role in maintenance of stem cells in vitro. We employed CRISPR-Cas9 targeting and generated stable mutant SSC lines with complete loss of Ephb2. The characteristics of Ephb2-KO cells were interrogated using phenotypic and functional assays. Ephb2-KO SSCs exhibited reduced proliferation compared to wild-type cells, while apoptosis was unaffected. Therefore, we examined whether Ephb2 loss correlates with activity of canonical pathways involved in stem cell self-renewal and proliferation. Ephb2-KO cells had reduced ERK MAPK signaling. Using a lentiviral transgene, Ephb2 expression was rescued in Ephb2-KO cells, which partially restored signaling and proliferation. Transplantation analysis revealed that Ephb2-KO SSCs cultures formed significantly fewer colonies than WT, indicating a role for Ephb2 in preserving stem cell activity of cultured cells. Transcriptome analysis of wild-type and Ephb2-KO SSCs identified Dppa4 and Bnc1 as differentially expressed, Ephb2-dependent genes that are potentially involved in stem cell function. These data uncover for the first time a crucial role for Ephb2 signaling in cultured SSCs.

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