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.

BMP signaling patterns the dorsal and intermediate neural tube via regulation of homeobox and helix-loop-helix transcription factors

Development ◽  
2002 ◽  
Vol 129 (10) ◽  
pp. 2459-2472 ◽  
Author(s):  
John R. Timmer ◽  
Charlotte Wang ◽  
Lee Niswander
Keyword(s):  
Transcription Factors ◽  
Neural Tube ◽  
Transforming Growth Factor ◽  
Cell Types ◽  
Neural Cell ◽  
Bmp Signaling ◽  
Expression Domain ◽  
Cell Identity ◽  
Dorsoventral Axis ◽  
Helix Loop Helix

In the spinal neural tube, populations of neuronal precursors that express a unique combination of transcription factors give rise to specific classes of neurons at precise locations along the dorsoventral axis. Understanding the patterning mechanisms that generate restricted gene expression along the dorsoventral axis is therefore crucial to understanding the creation of diverse neural cell types. Bone morphogenetic proteins (BMPs) and other transforming growth factor β (TGFβ) proteins are expressed by the dorsal-most cells of the neural tube (the roofplate) and surrounding tissues, and evidence indicates that they play a role in assigning cell identity. We have manipulated the level of BMP signaling in the chicken neural tube to show that BMPs provide patterning information to both dorsal and intermediate cells. BMP regulation of the expression boundaries of the homeobox proteins Pax6, Dbx2 and Msx1 generates precursor populations with distinct developmental potentials. Within the resulting populations, thresholds of BMP act to set expression domain boundaries of developmental regulators of the homeobox and basic helix-loop-helix (bHLH) families, ultimately leading to the generation of a diversity of differentiated neural cell types. This evidence strongly suggests that BMPs are the key regulators of dorsal cell identity in the spinal neural tube.

scholarly journals The Pituitary Function of Androgen Receptor Constitutes a Glucocorticoid Production Circuit

2007 ◽  
Vol 27 (13) ◽  
pp. 4807-4814 ◽  
Author(s):  
Junko Miyamoto ◽  
Takahiro Matsumoto ◽  
Hiroko Shiina ◽  
Kazuki Inoue ◽  
Ichiro Takada ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Negative Feedback ◽  
Late Onset ◽  
Feedback Regulation ◽  
Feedback System ◽  
Cell Types ◽  
Positive Control ◽  
Negative Feedback Regulation ◽  
Pituitary Glands ◽  
Glucocorticoid Production

ABSTRACT Androgen receptor (AR) mediates diverse androgen actions, particularly reproductive processes in males and females. AR-mediated androgen signaling is considered to also control metabolic processes; however, the molecular basis remains elusive. In the present study, we explored the molecular mechanism of late-onset obesity in male AR null mutant (ARKO) mice. We determined that the obesity was caused by a hypercorticoid state. The negative feedback system regulating glucocorticoid production was impaired in ARKO mice. Male and female ARKO mice exhibited hypertrophic adrenal glands and glucocorticoid overproduction, presumably due to high levels of adrenal corticotropic hormone. The pituitary glands of the ARKO males had increased expression of proopiomelanocortin and decreased expression of the glucocorticoid receptor (GR). There were no overt structural abnormalities and no alteration in the distribution of cell types in the pituitaries of male ARKO mice. Additionally, there was normal production of the other hormones within the glucocorticoid feedback system in both the pituitary and hypothalamus. In a cell line derived from pituitary glands, GR expression was under the positive control of the activated AR. Thus, this study suggests that the activated AR supports the negative feedback regulation of glucocorticoid production via up-regulation of GR expression in the pituitary gland.

scholarly journals Universal principles of lineage architecture and stem cell identity in renewing tissues

2020 ◽  
Author(s):  
Philip Greulich ◽  
Ben D. MacArthur ◽  
Cristina Parigini ◽  
Rubén J. Sánchez-García
Keyword(s):  
Stem Cell ◽  
Cell Lineage ◽  
Adult Stem Cell ◽  
Feedback Regulation ◽  
Cell Types ◽  
Universal Principles ◽  
Formal Framework ◽  
Cell Niche ◽  
Multicellular Organisms ◽  
The Relationship

Adult tissues in multicellular organisms typically contain a variety of stem, progenitor and differentiated cell types arranged in a lineage hierarchy that regulates healthy tissue turnover and repair. Lineage hierarchies in disparate tissues often exhibit common features, yet the general principles regulating their architecture are not known. Here, we provide a formal framework for understanding the relationship between cell molecular ‘states’ (patterns of gene, protein expression etc. in the cell) and cell ‘types’ that uses notions from network science to decompose the structure of cell state trajectories into functional units. Using this framework we show that many widely experimentally observed features of cell lineage architectures – including the fact that a single adult stem cell type always resides at the apex of a lineage hierarchy – arise as a natural consequence of homeostasis, and indeed are the only possible way that lineage architectures can be constructed to support homeostasis in renewing tissues. Furthermore, under suitable feedback regulation, for example from the stem cell niche, we show that the property of ‘stemness’ is entirely determined by the cell environment. Thus, we argue that stem cell identities are contextual and not determined by hard-wired, cell-intrinsic, characteristics.

scholarly journals Stem cells in the adult pancreas and liver

2007 ◽  
Vol 404 (2) ◽  
pp. 169-178 ◽  
Author(s):  
Zoë D. Burke ◽  
Shifaan Thowfeequ ◽  
Macarena Peran ◽  
David Tosh
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transcription Factors ◽  
Liver Failure ◽  
Adult Stem Cells ◽  
Cellular Therapy ◽  
Cell Types ◽  
Cell Compartment ◽  
Stem Cell Compartment ◽  
Undifferentiated Cells

Stem cells are undifferentiated cells that can self-renew and generate specialized (functional) cell types. The remarkable ability of stem cells to differentiate towards functional cells makes them suitable modalities in cellular therapy (which means treating diseases with the body's own cells). Potential targets for cellular therapy include diabetes and liver failure. However, in order for stem cells to be clinically useful, we must learn to identify them and to regulate their differentiation. We will use the intestine as a classical example of a stem cell compartment, and then examine the evidence for the existence of adult stem cells in two endodermally derived organs: pancreas and liver. We will review the characteristics of the putative stem cells in these tissues and the transcription factors controlling their differentiation towards functional cell types.

scholarly journals Universal principles of lineage architecture and stem cell identity in renewing tissues

Development ◽  
2021 ◽  
Vol 148 (11) ◽  
Author(s):  
Philip Greulich ◽  
Ben D. MacArthur ◽  
Cristina Parigini ◽  
Rubén J. Sánchez-García
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Feedback Regulation ◽  
Cell Types ◽  
Universal Principles ◽  
The People ◽  
Formal Framework ◽  
Cell Niche ◽  
Multicellular Organisms ◽  
The Relationship

ABSTRACT Adult tissues in multicellular organisms typically contain a variety of stem, progenitor and differentiated cell types arranged in a lineage hierarchy that regulates healthy tissue turnover. Lineage hierarchies in disparate tissues often exhibit common features, yet the general principles regulating their architecture are not known. Here, we provide a formal framework for understanding the relationship between cell molecular ‘states’ and cell ‘types’, based on the topology of admissible cell state trajectories. We show that a self-renewing cell type – if defined as suggested by this framework – must reside at the top of any homeostatic renewing lineage hierarchy, and only there. This architecture arises as a natural consequence of homeostasis, and indeed is the only possible way that lineage architectures can be constructed to support homeostasis in renewing tissues. Furthermore, under suitable feedback regulation, for example from the stem cell niche, we show that the property of ‘stemness’ is entirely determined by the cell environment, in accordance with the notion that stem cell identities are contextual and not determined by hard-wired, cell-intrinsic characteristics. This article has an associated ‘The people behind the papers’ interview.

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

2018 ◽  
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 ◽  
Quiescent Center ◽  
Specialized Cell ◽  
Complex Stoichiometry ◽  
Active Population ◽  
Stem Cell Divisions

AbstractStem cells divide and differentiate to form all the specialized cell types in a multicellular organism. In the Arabidopsis root, 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 (ODE) 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 is associated with more CEI division but less QC division. Further, our model prediction allowed us to establish the timing of QC and CEI division and propose that SHR repression of QC division depends on the formation of 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 ROS amplification drives mouse spermatogonial stem cell self-renewal

2019 ◽  
Vol 2 (2) ◽  
pp. e201900374 ◽  
Author(s):  
Hiroko Morimoto ◽  
Mito Kanastu-Shinohara ◽  
Narumi Ogonuki ◽  
Satoshi Kamimura ◽  
Atsuo Ogura ◽  
...  
Keyword(s):  
Stem Cell ◽  
Transcription Factors ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Nuclear Translocation ◽  
Cell Types ◽  
Spermatogonial Stem Cell ◽  
Self Renewal ◽  
Positive Feedback Loop ◽  
Chemical Screening

Reactive oxygen species (ROS) play critical roles in self-renewal division for various stem cell types. However, it remains unclear how ROS signals are integrated with self-renewal machinery. Here, we report that the MAPK14/MAPK7/BCL6B pathway creates a positive feedback loop to drive spermatogonial stem cell (SSC) self-renewal via ROS amplification. The activation of MAPK14 induced MAPK7 phosphorylation in cultured SSCs, and targeted deletion of Mapk14 or Mapk7 resulted in significant SSC deficiency after spermatogonial transplantation. The activation of this signaling pathway not only induced Nox1 but also increased ROS levels. Chemical screening of MAPK7 targets revealed many ROS-dependent spermatogonial transcription factors, of which BCL6B was found to initiate ROS production by increasing Nox1 expression via ETV5-induced nuclear translocation. Because hydrogen peroxide or Nox1 transfection also induced BCL6B nuclear translocation, our results suggest that BCL6B initiates and amplifies ROS signals to activate ROS-dependent spermatogonial transcription factors by forming a positive feedback loop.

scholarly journals Self-confined expression in the Arabidopsis root stem cell niche

2021 ◽  
Author(s):  
Josep Mercadal ◽  
Isabel Betegón-Putze ◽  
Nadja Bosch ◽  
Ana I. Caño-Delgado ◽  
Marta Ibañes
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Primary Root ◽  
Small Region ◽  
General Mechanism ◽  
Expression Domain ◽  
Arabidopsis Root ◽  
Root Stem Cell ◽  
Unique Identity ◽  
Cell Niche

AbstractStem cell niches are local microenvironments that preserve their unique identity while communicating with adjacent tissues. In the primary root of Arabidopsis thaliana, the stem cell niche comprises the expression of two transcription factors, BRAVO and WOX5, among others. Intriguingly, these proteins confine their own gene expression to the niche, as evidenced in each mutant background. Here we propose through mathematical modeling that BRAVO confines its own expression domain to the stem cell niche by attenuating its WOX5-dependent diffusible activator. This negative feedback drives WOX5 action to be spatially restricted as well. The results show that WOX5 diffusion and sequestration by binding to BRAVO is sufficient to drive realistic confined BRAVO expression at the stem cell niche. We propose that attenuation of a diffusible activator can be a general mechanism to confine genetic activity to a small region while at the same time maintain signaling within it and with the surrounding cells.

scholarly journals Arabidopsis Poly(ADP-ribose)-binding protein RCD1 interacts with Photoregulatory Protein Kinases in nuclear bodies

2020 ◽  
Author(s):  
Julia P. Vainonen ◽  
Alexey Shapiguzov ◽  
Julia Krasensky-Wrzaczek ◽  
Raffaella De Masi ◽  
Richard Gossens ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Signaling Pathways ◽  
Protein Kinases ◽  
Plant Stress ◽  
Nuclear Bodies ◽  
Dependent Manner ◽  
Stress Reactions ◽  
Transcriptional Responses ◽  
Environmental Signals ◽  
Intrinsically Disordered

AbstractContinuous reprograming of gene expression in response to environmental signals in plants is achieved through signaling hub proteins that integrate external stimuli and transcriptional responses. RADICAL-INDUCED CELL DEATH1 (RCD1) functions as a nuclear hub protein, which interacts with a variety of transcription factors with its C-terminal RST domain and thereby acts as a co-regulator of numerous plant stress reactions. Here a previously function for RCD1 as a novel plant PAR reader protein is shown; RCD1 functions as a scaffold protein, which recruits transcription factors to specific locations inside the nucleus in PAR-dependent manner. The N-terminal WWE- and PARP-like domains of RCD1 bind poly(ADP-ribose) (PAR) and determine its localization to nuclear bodies (NBs), which is prevented by chemical inhibition of PAR synthesis. RCD1 also binds and recruits Photoregulatory Protein Kinases (PPKs) to NBs. The PPKs, which have been associated with circadian clock, abscisic acid, and light signaling pathways, phosphorylate RCD1 at multiple sites in the intrinsically disordered region between the WWE- and PARP-like-domains, which affects the stability and function of RCD1 in the nucleus. Phosphorylation of RCD1 by PPKs provides a mechanism where turnover of a PAR-binding transcriptional co-regulator is controlled by nuclear phosphorylation signaling pathways.

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.

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