scholarly journals Positive feedback and feedforward loops between PERIANTHIA, WUSCHEL-RELATED HOMEOBOX5 and GRF-INTERACTING FACTOR 1 modulate gene expression and function in the Arabidopsis root

2018 ◽  
Author(s):  
Adam Paul Fisher ◽  
Natalie Minako Clark ◽  
Rosangela Sozzani
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Positive Feedback ◽  
Equation Model ◽  
Quiescent Center ◽  
Temporal Expression ◽  
Differential Equation Model ◽  
Arabidopsis Root ◽  
Gene Regulatory ◽  
And Function

AbstractThe Arabidopsis root meristem consists of populations of stem cells that surround the mitotically less active cells known as the Quiescent Center (QC). The QC maintains the stem cells in a non-cell-autonomous manner through the function of the transcription factor (TF) WUSCHEL-RELATED HOMEOBOX5 (WOX5), which is required for columella stem cell (CSC) maintenance. However, whether WOX5 has a regulatory role in any other adjacent stem cells is less understood. To this end, we identified a set of TFs downstream of WOX5 in both QC and Cortex Endodermis Initial (CEI) cells. We then utilized Gene Regulatory Network (GRN) inference to identify GRF-INTERACTING FACTOR 1 (GIF1) as a key gene involved in positive feedback and feedforward loops with WOX5 as well as another stem cell regulator, PERIANTHIA (PAN). Finally, we constructed an ordinary differential equation model based on this inferred GRN to simulate GIF1, PAN, and WOX5 expression over time, which suggests the precise temporal expression of WOX5 and GIF1 is important to sustain QC function.

scholarly journals Predicting gene regulatory networks by combining spatial and temporal gene expression data in Arabidopsis root stem cells

2017 ◽  
Vol 114 (36) ◽  
pp. E7632-E7640 ◽  
Author(s):  
Maria Angels de Luis Balaguer ◽  
Adam P. Fisher ◽  
Natalie M. Clark ◽  
Maria Guadalupe Fernandez-Espinosa ◽  
Barbara K. Möller ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Stem Cells ◽  
Stem Cell ◽  
Regulatory Networks ◽  
Network Inference ◽  
Quiescent Center ◽  
Cell Regulation ◽  
Gene Regulatory Network Inference ◽  
Stem Cell Regulation ◽  
Gene Regulatory

Identifying the transcription factors (TFs) and associated networks involved in stem cell regulation is essential for understanding the initiation and growth of plant tissues and organs. Although many TFs have been shown to have a role in the Arabidopsis root stem cells, a comprehensive view of the transcriptional signature of the stem cells is lacking. In this work, we used spatial and temporal transcriptomic data to predict interactions among the genes involved in stem cell regulation. To accomplish this, we transcriptionally profiled several stem cell populations and developed a gene regulatory network inference algorithm that combines clustering with dynamic Bayesian network inference. We leveraged the topology of our networks to infer potential major regulators. Specifically, through mathematical modeling and experimental validation, we identified PERIANTHIA (PAN) as an important molecular regulator of quiescent center function. The results presented in this work show that our combination of molecular biology, computational biology, and mathematical modeling is an efficient approach to identify candidate factors that function in the stem cells.

scholarly journals Protein complex stoichiometry and expression dynamics of transcription factors modulate stem cell division

2020 ◽  
Vol 117 (26) ◽  
pp. 15332-15342 ◽  
Author(s):  
Natalie M. Clark ◽  
Adam P. Fisher ◽  
Barbara Berckmans ◽  
Lisa Van den Broeck ◽  
Emily C. Nelson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Model Prediction ◽  
Protein Complex ◽  
Cell Types ◽  
Equation Model ◽  
Quiescent Center ◽  
Specialized Cell ◽  
Complex Stoichiometry ◽  
Stem Cell Divisions

Stem cells divide and differentiate to form all of the specialized cell types in a multicellular organism. In theArabidopsisroot, stem cells are maintained in an undifferentiated state by a less mitotically active population of cells called the quiescent center (QC). Determining how the QC regulates the surrounding stem cell initials, or what makes the QC fundamentally different from the actively dividing initials, is important for understanding how stem cell divisions are maintained. Here we gained insight into the differences between the QC and the cortex endodermis initials (CEI) by studying the mobile transcription factor SHORTROOT (SHR) and its binding partner SCARECROW (SCR). We constructed an ordinary differential equation model of SHR and SCR in the QC and CEI which incorporated the stoichiometry of the SHR-SCR complex as well as upstream transcriptional regulation of SHR and SCR. Our model prediction, coupled with experimental validation, showed that high levels of the SHR-SCR complex are associated with more CEI division but less QC division. Furthermore, our model prediction allowed us to propose the putative upstream SHR regulators SEUSS and WUSCHEL-RELATED HOMEOBOX 5 and to experimentally validate their roles in QC and CEI division. In addition, our model established the timing of QC and CEI division and suggests that SHR repression of QC division depends on formation of the SHR homodimer. Thus, our results support that SHR-SCR protein complex stoichiometry and regulation of SHR transcription modulate the division timing of two different specialized cell types in the root stem cell niche.

scholarly journals An inference approach combines spatial and temporal gene expression data to predict gene regulatory networks in Arabidopsis stem cells

2017 ◽  
Author(s):  
Maria Angels de Luis Balaguer ◽  
Adam P. Fisher ◽  
Natalie M. Clark ◽  
Maria Guadalupe Fernandez-Espinosa ◽  
Barbara K. Möller ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Stem Cells ◽  
Stem Cell ◽  
Regulatory Networks ◽  
Dynamic Bayesian Network ◽  
Quiescent Center ◽  
Cell Regulation ◽  
Stem Cell Regulation ◽  
Transcriptional Signature ◽  
Gene Regulatory

AbstractIdentifying the transcription factors (TFs) and associated networks involved in stem cell regulation is key for understanding the initiation and growth of plant tissues and organs. Although many TFs have been shown to have a role in the Arabidopsis root stem cells, a comprehensive view of the transcriptional signature of the stem cells is lacking. In this work, we used spatial and temporal transcriptomic data to predict interactions among the genes involved in stem cell regulation. For this, we transcriptionally profiled several stem cell populations and developed a gene regulatory network (GRN) inference algorithm that combines clustering with Dynamic Bayesian Network (DBN) inference. We leveraged the topology of our networks to infer potential key regulators. The results presented in this work show that our combination of molecular biology approaches, computational biology and mathematical modeling was key to identify candidate factors that function in the stem cells. Specifically, through experimental validation and mathematical modeling, we identified PERIANTHIA (PAN) as an important molecular regulator of quiescent center (QC) function.

Distribution of amniotic stem cells in human term amnion membrane

Microscopy ◽  
2021 ◽  
Author(s):  
Nobuyuki Koike ◽  
Jun Sugimoto ◽  
Motonori Okabe ◽  
Kenichi Arai ◽  
Makiko Nogami ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Markers ◽  
Epithelial Stem Cells ◽  
Human Amnion ◽  
Transporter Protein ◽  
Amniotic Mesenchymal Stem Cells ◽  
Amnion Membrane ◽  
And Function ◽  
A Site

Abstract Amnion membrane studies related to miscarriage have been conducted in the field of obstetrics and gynecology. However, the distribution of stem cells within the amnion and the differences in the properties of each type of stem cells are still not well understood. We address this gap in knowledge in the present study where we morphologically classified the amnion membrane, and we clarified the distribution of stem cells here to identify functionally different amniotic membrane–derived stem cells. The amnion can be divided into a site that is continuous with the umbilical cord (region A), a site that adheres to the placenta (region B), and a site that is located opposite the placenta (region C). We found that human amnion epithelial stem cells (HAECs) that strongly express stem cell markers were abundant in area A. HAEC not only expressesed stem cell-specific surface markers TRA-1-60, Tra-1-81, SSEA4, SSEA3, but was also OCT-3/4 positive and had alkaline phosphatase activity. Human amniotic mesenchymal stem cells expressed KLF-A, OCTA, Oct3/4, c-MYC and Sox2 which is transcription factor. Especially, in regions A and B they have expressed CD73, and the higher expression of BCRP which is drug excretion transporter protein than the other parts. These data suggest that different types of stem cells may have existed in different area. The understanding the relation with characteristics of the stem cells in each area and function would allow for the efficient harvest of suitable HAE and HAM stem cells as using tool for regenerative medicine.

Abstract 253: The Presence of Coronary Artery Disease Influences Number and Function of Stem Cells in the Bone Marrow

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Evelien Nollet ◽  
Dina De Bock ◽  
Inez R Rodrigus ◽  
Vicky Y Hoymans ◽  
Christiaan J Vrints ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Stem Cells ◽  
Bone Marrow ◽  
Renal Function ◽  
Stem Cell ◽  
Coronary Artery ◽  
Therapeutic Benefits ◽  
Migratory Capacity ◽  
Artery Disease ◽  
And Function

Purpose: Despite the observed therapeutic benefits of autologous bone marrow (BM)-derived stem cell transplantation in patients with ischemic heart disease, the efficacy of this approach could be hampered by BM dysfunction. We investigated whether BM cellularity and function is affected by coronary artery disease (CAD). Methods & Results: BM samples were obtained peri-operatively from 26 CAD patients, undergoing coronary artery bypass surgery (LVEF 54±16%), and 6 controls, undergoing mitral valve surgery (LVEF 50±12%; age 59±10yrs). CAD patients were stratified according to their Syntax score (mild ≤15, age 61±10yrs; and moderate CAD >15, age 63±8yrs; stratification based on median score), which is used to assess complexity of coronary lesions. In vitro functional analysis of isolated BM-derived mononuclear cells (BM-MNC) revealed a significant impairment of migratory capacity towards SDF-1α and VEGF in patients with moderate CAD (25.71±7.3%) compared to controls (33.82±8.3%; p=0.042) and patients with mild CAD (34.76±7.8%; p=0.007). Hematopoetic stem cells (HSC, CD45dimCD34+SSClow) were reduced in patients with moderate CAD (8178±5530 HSC/106 BM-MNC; p=0.014) and mild CAD (10655±5489 HSC/106 BM-MNC; p=0.054) compared to controls (16220±6126 HSC/106 BM-MNC). An inverse correlation was found between age and the number of granulocyte-macrophage colony forming units (r= −0.408; p=0.048), burst forming units erythroid (r= −0.458; p=0.028) and HSC (r=-0.356; p=0.046). Furthermore, our data revealed a relation between reduced renal function (CKD-EPI eGFR, 81.2±19 ml/min) and reduced number of HSC (r=0.480; p=0.011) and endothelial progenitor cells (EPC, CD45dimCD34+KDR+; r=0.522; p=0.008). Conclusions: Migratory capacity of BM-MNC and the number of HSC are reduced in patients with CAD, which is more pronounced in more complex CAD. In addition, age and renal function emerge as relevant determinants on BM function and stem cell populations. Therefore, these factors should be taken into account when assessing benefits of autologous stem cell therapy.

scholarly journals Symplastic communication spatially directs local auxin biosynthesis to maintain root stem cell niche in Arabidopsis

2017 ◽  
Vol 114 (15) ◽  
pp. 4005-4010 ◽  
Author(s):  
Yuting Liu ◽  
Meizhi Xu ◽  
Nengsong Liang ◽  
Yanghang Zheng ◽  
Qiaozhi Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Cell Communication ◽  
Positional Information ◽  
Auxin Biosynthesis ◽  
Root Tip ◽  
Quiescent Center ◽  
Stem Cell Maintenance ◽  
Cell Niche

Stem cells serve as the source of new cells for plant development. A group of stem cells form a stem cell niche (SCN) at the root tip and in the center of the SCN are slowly dividing cells called the quiescent center (QC). QC is thought to function as a signaling hub that inhibits differentiation of surrounding stem cells. Although it has been generally assumed that cell-to-cell communication provides positional information for QC and SCN maintenance, the tools for testing this hypothesis have long been lacking. Here we exploit a system that effectively blocks plasmodesmata (PD)-mediated signaling to explore how cell-to-cell communication functions in the SCN. We showed that the symplastic signaling between the QC and adjacent cells directs the formation of local auxin maxima and establishment of AP2-domain transcription factors, PLETHORA gradients. Interestingly we found symplastic signaling is essential for local auxin biosynthesis, which acts together with auxin polar transport to provide the guidance for local auxin enrichment. Therefore, we demonstrate the crucial role of cell-to-cell communication in the SCN maintenance and further uncover a mechanism by which symplastic signaling initiates and reinforces the positional information during stem cell maintenance via auxin regulation.

Constructing stem cell microenvironments using bioengineering approaches

2013 ◽  
Vol 45 (23) ◽  
pp. 1123-1135 ◽  
Author(s):  
David A. Brafman
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Disease Modeling ◽  
Mechanical Stimuli ◽  
Culture Methods ◽  
Stem Cell Fate ◽  
And Function

Within the adult organism, stem cells reside in defined anatomical microenvironments called niches. These architecturally diverse microenvironments serve to balance stem cell self-renewal and differentiation. Proper regulation of this balance is instrumental to tissue repair and homeostasis, and any imbalance can potentially lead to diseases such as cancer. Within each of these microenvironments, a myriad of chemical and physical stimuli interact in a complex (synergistic or antagonistic) manner to tightly regulate stem cell fate. The in vitro replication of these in vivo microenvironments will be necessary for the application of stem cells for disease modeling, drug discovery, and regenerative medicine purposes. However, traditional reductionist approaches have only led to the generation of cell culture methods that poorly recapitulate the in vivo microenvironment. To that end, novel engineering and systems biology approaches have allowed for the investigation of the biological and mechanical stimuli that govern stem cell fate. In this review, the application of these technologies for the dissection of stem cell microenvironments will be analyzed. Moreover, the use of these engineering approaches to construct in vitro stem cell microenvironments that precisely control stem cell fate and function will be reviewed. Finally, the emerging trend of using high-throughput, combinatorial methods for the stepwise engineering of stem cell microenvironments will be explored.

scholarly journals An orthogonal differentiation platform for genomically programming stem cells, organoids, and bioprinted tissues

2020 ◽  
Author(s):  
Mark A. Skylar-Scott ◽  
Jeremy Y. Huang ◽  
Aric Lu ◽  
Alex H.M. Ng ◽  
Tomoya Duenki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Embryoid Bodies ◽  
One Pot ◽  
Neural Tissues ◽  
Induced Pluripotent ◽  
And Function ◽  
Matrix Free

AbstractSimultaneous differentiation of human induced pluripotent stem cells (hiPSCs) into divergent cell types offers a pathway to achieving tailorable cellular complexity, patterned architecture, and function in engineered human organoids and tissues. Recent transcription factor (TF) overexpression protocols typically produce only one cell type of interest rather than the multitude of cell types and structural organization found in native human tissues. Here, we report an orthogonal differentiation platform for genomically programming stem cells, organoids and bioprinted tissues with controlled composition and organization. To demonstrate this platform, we orthogonally differentiated endothelial cells and neurons from hiPSCs in a one-pot system containing neural stem cell-specifying media. By aggregating inducible-TF and wildtype hiPSCs into pooled and multicore-shell embryoid bodies, we produced vascularized and patterned cortical organoids within days. Using multimaterial 3D bioprinting, we patterned 3D neural tissues from densely cellular, matrix-free stem cell inks that were orthogonally differentiated on demand into distinct layered regions composed of neural stem cells, endothelium, and neurons, respectively. Given the high proliferative capacity and patient-specificity of hiPSCs, our platform provides a facile route for programming cells and multicellular tissues for drug screening and therapeutic applications.

scholarly journals PLETHORA and WOX5 interaction and subnuclear localisation regulates Arabidopsis root stem cell maintenance

2019 ◽  
Author(s):  
Rebecca C. Burkart ◽  
Vivien I. Strotmann ◽  
Gwendolyn K. Kirschner ◽  
Abdullah Akinci ◽  
Laura Czempik ◽  
...  
Keyword(s):  
Stem Cell ◽  
Transcription Factors ◽  
Feedback Regulation ◽  
Cell Types ◽  
Nuclear Bodies ◽  
Quiescent Center ◽  
Expression Domain ◽  
Negative Feedback Regulation ◽  
Arabidopsis Root ◽  
Intrinsically Disordered

Maintenance and homeostasis of the stem cell niche (SCN) in the Arabidopsis root is essential for growth and development of all root cell types. The SCN is organized around a quiescent center (QC) that maintains the stemness of the cells in direct contact. The transcription factors WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and the PLETHORAs (PLTs) are both expressed in the SCN where they maintain the QC and regulate the fate of the distal columella stem cells (CSCs). Although WOX5 and PLTs are known as important players in SCN maintenance, much of the necessary regulation of quiescence and division in the Arabidopsis root is not understood on a molecular level. Here, we describe the concerted mutual regulation of the key transcription factors WOX5 and PLTs on a transcriptional and protein interaction level, leading to a confinement of the WOX5 expression domain to the QC cells by negative feedback regulation. Additionally, by applying a novel SCN staining method, we demonstrate that both WOX5 and PLTs are necessary for root meristem maintenance as they regulate QC quiescence and CSC fate and show that QC divisions and CSC differentiation correlate. Moreover, we uncover that PLTs, especially PLT3, contains intrinsically disordered prion-like domains (PrDs) that are necessary for complex formation with WOX5 and its recruitment to subnuclear microdomains/nuclear bodies (NBs) in the CSCs. We propose that the partitioning of the PLT-WOX5 complexes to NBs, possibly by liquid-liquid phase separation, plays an important role during determination of CSC fate.

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