scholarly journals LIX1 controls digestive mesenchyme-derived cell fate decision by regulating cristae organization in mitochondria

2022 ◽  
Author(s):  
Amandine Guerin ◽  
Claire Angebault ◽  
Sandrina Kinet ◽  
Chantal Cazevieille ◽  
Manuel Rojo ◽  
...  
Keyword(s):  
Cell Fate ◽  
Unsaturated Fatty Acids ◽  
Cell Lineage ◽  
Mitochondrial Morphology ◽  
Knock Down ◽  
Fate Decision ◽  
Underlying Mechanisms ◽  
The Stability ◽  
Mitochondrial Remodeling ◽  
Species Production

Limb Expression 1 (LIX1) is a master regulator of digestive mesenchymal progenitor and GastroIntestinal Stromal Tumor (GIST) cell proliferation by controlling the expression of the Hippo effectors YAP1/TAZ and KIT. However, the underlying mechanisms of these LIX1- mediated regulations and tumor promotion remain to be elucidated. Here, we report that LIX1 is S-palmitoylated on cysteine 84 and localized in mitochondria. LIX1 knock-down affects the mitochondrial ultrastructure, resulting in decreased respiration and mitochondrial reactive oxygen species production. This is sufficient to downregulate YAP1/TAZ and reprogram KIT- positive GIST cells towards the smooth muscle cell lineage with reduced proliferative and invasive capacities. Mechanistically, LIX1 knock-down impairs the stability of the mitochondrial proteins PHB2 and OPA1 that are found in complexes with mitochondrial- specific phospholipids and are required for cristae organization. Supplementation with unsaturated fatty acids counteracts the effects of LIX1 knock-down on mitochondrial morphology and ultrastructure, restores YAP1/TAZ signaling, and consequently KIT levels. Altogether, our findings demonstrate that LIX1 contributes to GIST aggressive potential by modulating YAP1/TAZ and KIT levels, a process that depends on mitochondrial remodeling. Our work brings new insights into the mechanisms that could be targeted in tumors in which YAP1 and TAZ are implicated.

scholarly journals Cell fate clusters in ICM organoids arise from cell fate heredity and division: a modelling approach

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tim Liebisch ◽  
Armin Drusko ◽  
Biena Mathew ◽  
Ernst H. K. Stelzer ◽  
Sabine C. Fischer ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Division ◽  
Cell Fate ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Cell Lineage ◽  
Cell Fate Decision ◽  
Cell Fate Decisions ◽  
Chemical Signalling ◽  
Fate Decision

AbstractDuring the mammalian preimplantation phase, cells undergo two subsequent cell fate decisions. During the first decision, the trophectoderm and the inner cell mass are formed. Subsequently, the inner cell mass segregates into the epiblast and the primitive endoderm. Inner cell mass organoids represent an experimental model system, mimicking the second cell fate decision. It has been shown that cells of the same fate tend to cluster stronger than expected for random cell fate decisions. Three major processes are hypothesised to contribute to the cell fate arrangements: (1) chemical signalling; (2) cell sorting; and (3) cell proliferation. In order to quantify the influence of cell proliferation on the observed cell lineage type clustering, we developed an agent-based model accounting for mechanical cell–cell interaction, i.e. adhesion and repulsion, cell division, stochastic cell fate decision and cell fate heredity. The model supports the hypothesis that initial cell fate acquisition is a stochastically driven process, taking place in the early development of inner cell mass organoids. Further, we show that the observed neighbourhood structures can emerge solely due to cell fate heredity during cell division.

Identification of Bipotent Basophil/Mast Cell Progenitors in Adult Murine Hematopoiesis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 633-633
Author(s):  
Yojiro Arinobu ◽  
Hiromi Iwasaki ◽  
Michael F. Gurish ◽  
Shinichi Mizuno ◽  
Hirokazu Shigematsu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Cell Fate ◽  
Bone Marrow Cells ◽  
Cell Lineage ◽  
Primary Role ◽  
Peripheral Tissues ◽  
Fate Decision

Abstract Basophils and mast cells are multifunctional hematopoietic effectors that co-operate to mount a variety of allergic and innate immune responses. Their origin and developmental relationships, however, have not yet been resolved, and remain as one of the major issues in the biology of hematopoiesis. Here we report that progenitors bipotent for basophils and mast cells(basophil/mast cell progenitors: BMCPs) are prospectively isolatable within murine spleen. We have shown that the β7-integrin(β7) is an essential molecule for tissue-specific homing of putative precursors for intestinal mast cells (J Exp Med194:1243, 2001). To identify a candidate population that seeds intestinal progenitors for mast cells, we searched for β7+ cells in the bone marrow and the spleen. Lin−c-Kit+ spleen cells contained a fraction of cells expressing β7 at high levels. They also expressed FcγRII/III, but the majority of these cells did not express FcεRIα. These Lin−c-Kit+FcγRII/III+β7hiFcεRIα−/locells exclusively differentiated into mature mast cells and basophils. Strikingly, single Lin−c-Kit+FcγRII/III+β7hiFcεRIα−/locells formed colonies containing both basophils and mast cells as well as pure mast cell or basophil colonies. We thus named these cells as BMCPs. In 2-day cultures, purified BMCPs upregulated FcεRIα, giving rise to Lin−CD34+FcεRIαhic-Kit+ and Li− CD34+FcεRIαhic-Kit− blastic cell populations, and they differentiated exclusively into mast cells and basophils, respectively. Based on this phenotype, we searched for precursors committed to either lineage in vivo. The Lin−CD34+ bone marrow cells contained FcεRIαhic-Kit−cells, which differentiated exclusively into basophils. We named this population as basophil progenitors (BaPs). Since mast cell progenitors(MCPs) were not isolatable as a distinct population in the bone marrow or the spleen, we searched for MCPs in the intestine. We newly identified CD45+Li− CD34+β7hiFcεRIαlocells in the intestine, and these cells exclusively formed pure mast cell colonies, which were named as intestinal MCPs. Since the expression of C/EBPα was dramatically increased in BaPs but was downregulated in MCPs, we hypothesized that it plays a key role in the basophil versus the mast cell lineage commitment. To test this hypothesis, we disrupted or overexpressed C/EBPα at the BMCP stage. BMCPs disrupted with C/EBPα gave rise exclusively to mast cells, while, BMCPs overexpressing C/EBPα differentiated mainly into basophils, suggesting that C/EBPα plays a primary role in deciding the basophil vs. mast cell fate at the BMCP stage. Thus, differentiation of the BMCPs into committed progeny may lead to selective migration, BaPs to the bone marrow or MCPs to peripheral tissues, and this fate decision is controlled principally by C/EBPα. These newly identified progenitors should be useful to analyze the mechanism of commitment into each of these lineages, and could also be therapeutic targets for a variety of allergic and autoimmune disorders.

scholarly journals Differential Effects of Notch Ligands Delta-1 and Jagged-1 in Human Lymphoid Differentiation

2001 ◽  
Vol 194 (7) ◽  
pp. 991-1002 ◽  
Author(s):  
Ana C. Jaleco ◽  
Hélia Neves ◽  
Erik Hooijberg ◽  
Paula Gameiro ◽  
Nuno Clode ◽  
...  
Keyword(s):  
T Cell ◽  
Notch Signaling ◽  
Cell Fate ◽  
De Novo ◽  
Cell Lineage ◽  
Differential Effects ◽  
Cell Lineages ◽  
A Cell ◽  
Fate Decision ◽  
Notch Ligands

Notch signaling is known to differentially affect the development of lymphoid B and T cell lineages, but it remains unclear whether such effects are specifically dependent on distinct Notch ligands. Using a cell coculture assay we observed that the Notch ligand Delta-1 completely inhibits the differentiation of human hematopoietic progenitors into the B cell lineage while promoting the emergence of cells with a phenotype of T cell/natural killer (NK) precursors. In contrast, Jagged-1 did not disturb either B or T cell/NK development. Furthermore, cells cultured in the presence of either Delta-1 or Jagged-1 can acquire a phenotype of NK cells, and Delta-1, but not Jagged-1, permits the emergence of a de novo cell population coexpressing CD4 and CD8. Our results thus indicate that distinct Notch ligands can mediate differential effects of Notch signaling and provide a useful system to further address cell-fate decision processes in lymphopoiesis.

scholarly journals Epigenetic control of cell fate - an interview with Prof. Maria-Elena Torres-Padilla

2020 ◽  
Vol 52 ◽  
Author(s):  
Jesús Chimal-Monroy ◽  
Diana María Escalante-Alcalde
Keyword(s):  
Cell Fate ◽  
Cell Biology ◽  
Cell Lineage ◽  
Cellular Reprogramming ◽  
Cell Fate Decision ◽  
Cell Embryo ◽  
Founding Director ◽  
Fate Decision ◽  
The One ◽  
New Generation

Dr. Maria-Elena Torres-Padilla's research is focused on how cell fate arises from a single-cell embryo, the fertilized egg or zygote. After the initial divisions, cell potency becomes restricted, originating the first cell lineage fates. She studies how epigenetic information controls transitions in cell identity and cellular reprogramming during embryonic development. Currently, she is the founding Director of the Institute of Epigenetics and Stem Cells, Helmholtz Centre, and Professor of Stem Cell Biology at the LMU in Munich. In this interview, Dr. Maria-Elena Torres-Padilla talks to us about her beginnings in the biology field in Mexico. She also tells us about how she became interested in the control of genome regulation within the nucleus during the transition from totipotency to pluripotency and how the control of gene regulation and chromatin organization during the early stages of cell fate decision in the one-cell embryo occurs. She considers that science has no borders; visiting Mexico gives her the possibility to discuss her work with colleagues and the new generation of students trained in Mexico.

scholarly journals Biochemical and structural cues of 3D-printed matrix synergistically direct MSC differentiation for functional sweat gland regeneration

2020 ◽  
Vol 6 (10) ◽  
pp. eaaz1094 ◽  
Author(s):  
Bin Yao ◽  
Rui Wang ◽  
Yihui Wang ◽  
Yijie Zhang ◽  
Tian Hu ◽  
...  
Keyword(s):  
Cell Fate ◽  
Sweat Gland ◽  
Therapeutic Potential ◽  
3D Structure ◽  
Activation Assay ◽  
3D Printed ◽  
Fate Decision ◽  
Matrix Differential ◽  
Underlying Mechanisms ◽  
Msc Differentiation

Mesenchymal stem cells (MSCs) encapsulation by three-dimensionally (3D) printed matrices were believed to provide a biomimetic microenvironment to drive differentiation into tissue-specific progeny, which made them a great therapeutic potential for regenerative medicine. Despite this potential, the underlying mechanisms of controlling cell fate in 3D microenvironments remained relatively unexplored. Here, we bioprinted a sweat gland (SG)–like matrix to direct the conversion of MSC into functional SGs and facilitated SGs recovery in mice. By extracellular matrix differential protein expression analysis, we identified that CTHRC1 was a critical biochemical regulator for SG specification. Our findings showed that Hmox1 could respond to the 3D structure activation and also be involved in MSC differentiation. Using inhibition and activation assay, CTHRC1 and Hmox1 synergistically boosted SG gene expression profile. Together, these findings indicated that biochemical and structural cues served as two critical impacts of 3D-printed matrix on MSC fate decision into the glandular lineage and functional SG recovery.

scholarly journals Uncertainty in cell fate decision making: Lessons from potential landscapes of bifurcation systems

2021 ◽  
Author(s):  
Anissa Guillemin ◽  
Elisabeth Roesch ◽  
Michael P.H. Stumpf
Keyword(s):  
Decision Making ◽  
Cell Fate ◽  
Qualitative Change ◽  
Pictorial Representation ◽  
Cell Fate Decision ◽  
Ample Evidence ◽  
Molecular Noise ◽  
Intrinsic Complexity ◽  
Fate Decision ◽  
The Stability

AbstractCell fate decision making is known to be a complex process and is still far from being understood. The intrinsic complexity, but also features such as molecular noise represent challenges for modelling these systems. Waddington’s epigenetic landscape has become the overriding metaphor for developmental processes: it both serves as pictorial representation, and can be related to mathematical models. In this work we investigate how the landscape is affected by noise in the underlying system. Specifically, we focus on those systems where minor changes in the parameters cause major changes in the stability properties of the system, especially bifurcations. We analyse and quantify the changes in the landscape’s shape as the effects of noise increase. We find ample evidence for intricate interplay between noise and dynamics which can lead to qualitative change in a system’s dynamics and hence the corresponding landscape. In particular, we find that the effects can be most pronounced in the vicinity of the bifurcation point of the underlying deterministic dynamical systems, which would correspond to the cell fate decision event in cellular differentiation processes.

scholarly journals Aberrant Mitochondrial Dynamics: An Emerging Pathogenic Driver of Abdominal Aortic Aneurysm

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mingqi Ouyang ◽  
Mi Wang ◽  
Bilian Yu
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Cell Fate ◽  
Mitochondrial Dynamics ◽  
Oxygen Species ◽  
Abdominal Aortic ◽  
Mitochondrial Functions ◽  
Important Player ◽  
Underlying Mechanisms ◽  
Species Production

Abdominal aortic aneurysm (AAA) is defined as a progressive segmental dilation of the abdominal aorta and is associated with high mortality. The characterized features of AAA indicate several underlying mechanisms of AAA formation and progression, including reactive oxygen species production, inflammation, and atherosclerosis. Mitochondrial functions are critical for determining cell fate, and mitochondrial dynamics, especially selective mitochondrial autophagy, which is termed as mitophagy, has emerged as an important player in the pathogenesis of several cardiovascular diseases. The PARKIN/PARIS/PGC1α pathway is associated with AAA formation and has been proposed to play a role in mitochondrial dynamics mediated by the PINK/PARKIN pathway in the pathogenesis underlying AAA. This review is aimed at deepening our understanding of AAA formation and progression, which is vital for the development of potential medical therapies for AAA.

scholarly journals Polarized endosome dynamics engage cytosolic Par-3 and dynein during asymmetric division

2020 ◽  
Author(s):  
Xiang Zhao ◽  
Kai Tong ◽  
Xingye Chen ◽  
Bin Yang ◽  
Qi Li ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Radial Glia ◽  
Asymmetric Cell Division ◽  
Time Lapse ◽  
Cell Fate Decisions ◽  
Dynein Motor ◽  
Fate Decision ◽  
Underlying Mechanisms

AbstractAsymmetric cell division (ACD), which produces two daughters with different fates, is fundamental for generating cellular diversity. In the developing embryos of both invertebrates and vertebrates, asymmetrically dividing progenitors generate daughter cells with differential activity of Notch signaling1–7, a key regulator of cell fate decisions8,9. The cell polarity regulator Par-3 is critical for establishing this Notch asymmetry1,4,6, but the underlying mechanisms are not understood. Here, employing in vivo time-lapse imaging in the developing zebrafish forebrain during the mitotic cycle of radial glia, the principal vertebrate neural stem cells10,11, we show that during ACD, endosomes containing the Notch ligand Delta D (Dld) undergo convergent movement toward the cleavage plane, followed by preferential segregation into the posterior (and subsequently basal) Notchhi daughter. This asymmetric segregation requires the activity of Par-3 and the dynein motor complex. Employing label-retention expansion microscopy, we further detect Par-3 in the cytosol in association with the dynein light intermediate chain 1 (DLIC1) on Dld endosomes, suggesting a direct involvement of Par-3 in dynein-mediated polarized transport of Notch signaling endosomes. Our data reveal an unanticipated mechanism by which Par-3 regulates cell fate decision by directly polarizing Notch signaling components during ACD.

scholarly journals Runx1 regulates embryonic myeloid fate choice in zebrafish through a negative feedback loop inhibiting Pu.1 expression

Blood ◽  
2012 ◽  
Vol 119 (22) ◽  
pp. 5239-5249 ◽  
Author(s):  
Hao Jin ◽  
Li Li ◽  
Jin Xu ◽  
Fenghua Zhen ◽  
Lu Zhu ◽  
...  
Keyword(s):  
Cell Fate ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Wide Spectrum ◽  
Negative Feedback Loop ◽  
Fate Decision ◽  
Underlying Mechanisms ◽  
Regulatory Loop

Abstract Proper cell fate choice in myelopoiesis is essential for generating correct numbers of distinct myeloid subsets manifesting a wide spectrum of subset-specific activities during development and adulthood. Studies have suggested that myeloid fate choice is primarily regulated by transcription factors; however, new intrinsic regulators and their underlying mechanisms remain to be elucidated. Zebrafish embryonic myelopoiesis gives rise to neutrophils and macrophages and represents a promising system to derive new regulatory mechanisms for myeloid fate decision in vertebrates. Here we present an in vivo study of cell fate specification during zebrafish embryonic myelopoiesis through characterization of the embryos with altered Pu.1, Runx1 activity alone, or their combinations. Genetic analysis shows that low and high Pu.1 activities determine embryonic neutrophilic granulocyte and macrophage fate, respectively. Inactivation and overexpression of Runx1 in zebrafish uncover Runx1 as a key embryonic myeloid fate determinant that favors neutrophil over macrophage fate. Runx1 is induced by high Pu.1 level and in turn transrepresses pu.1 expression, thus constituting a negative feedback loop that fashions a favorable Pu.1 level required for balanced fate commitment to neutrophils versus macrophages. Our findings define a Pu.1-Runx1 regulatory loop that governs the equilibrium between distinct myeloid fates by assuring an appropriate Pu.1 dosage.

scholarly journals Regulatory network control of blood stem cells

Blood ◽  
2015 ◽  
Vol 125 (17) ◽  
pp. 2614-2620 ◽  
Author(s):  
Berthold Göttgens
Keyword(s):  
Decision Making ◽  
Stem Cells ◽  
Cell Fate ◽  
Regulatory Networks ◽  
Cell Types ◽  
Network Control ◽  
Hematopoietic Stem ◽  
Wide Range ◽  
Fate Decision ◽  
Underlying Mechanisms

Abstract Hematopoietic stem cells (HSCs) are characterized by their ability to execute a wide range of cell fate choices, including self-renewal, quiescence, and differentiation into the many different mature blood lineages. Cell fate decision making in HSCs, as indeed in other cell types, is driven by the interplay of external stimuli and intracellular regulatory programs. Given the pivotal nature of HSC decision making for both normal and aberrant hematopoiesis, substantial research efforts have been invested over the last few decades into deciphering some of the underlying mechanisms. Central to the intracellular decision making processes are transcription factor proteins and their interactions within gene regulatory networks. More than 50 transcription factors have been shown to affect the functionality of HSCs. However, much remains to be learned about the way in which individual factors are connected within wider regulatory networks, and how the topology of HSC regulatory networks might affect HSC function. Nevertheless, important progress has been made in recent years, and new emerging technologies suggest that the pace of progress is likely to accelerate. This review will introduce key concepts, provide an integrated view of selected recent studies, and conclude with an outlook on possible future directions for this field.

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