scholarly journals Regulation of stem cell identity by miR-200a during spinal cord regeneration

2021 ◽  
Author(s):  
Sarah Walker ◽  
Keith Sabin ◽  
Micah Gearhart ◽  
Kenta Yamamoto ◽  
Karen Echeverri
Keyword(s):  
Spinal Cord ◽  
Stem Cell ◽  
Cell Fate ◽  
Model Organism ◽  
Lineage Tracing ◽  
Stem Cell Marker ◽  
Small Lesion ◽  
Spinal Cord Regeneration ◽  
Mesodermal Cell

Axolotls are an important model organism for multiple types of regeneration, including functional spinal cord regeneration. Remarkably, axolotls can repair their spinal cord after a small lesion injury and can also regenerate their entire tail following amputation. Several classical signaling pathways that are used during development are reactivated during regeneration, but how this is regulated remains a mystery. We have previously identified miR-200a as a key factor that promotes successful spinal cord regeneration. Here, using RNA-seq analysis, we discovered that the inhibition of miR-200a results in an upregulation of the classical mesodermal marker brachyury in spinal cord cells after injury. However, these cells still express the neural stem cell marker sox2. In vivo lineage tracing allowed us to determine that these cells can give rise to cells of both the neural and mesoderm lineage. Additionally, we found that miR-200a can directly regulate brachyury via a seed sequence in the 3UTR of the gene. Our data indicate that miR-200a represses mesodermal cell fate after a small lesion injury in the spinal cord when only glial cells and neurons need to be replaced.

scholarly journals aPKCλ controls epidermal homeostasis and stem cell fate through regulation of division orientation

2013 ◽  
Vol 202 (6) ◽  
pp. 887-900 ◽  
Author(s):  
Michaela T. Niessen ◽  
Jeanie Scott ◽  
Julia G. Zielinski ◽  
Susanne Vorhagen ◽  
Panagiota A. Sotiropoulou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Lineage Tracing ◽  
Premature Aging ◽  
Temporary Increase ◽  
Proliferative Potential ◽  
Cell Dynamics ◽  
Asymmetric Divisions

The atypical protein kinase C (aPKC) is a key regulator of polarity and cell fate in lower organisms. However, whether mammalian aPKCs control stem cells and fate in vivo is not known. Here we show that loss of aPKCλ in a self-renewing epithelium, the epidermis, disturbed tissue homeostasis, differentiation, and stem cell dynamics, causing progressive changes in this tissue. This was accompanied by a gradual loss of quiescent hair follicle bulge stem cells and a temporary increase in proliferating progenitors. Lineage tracing analysis showed that loss of aPKCλ altered the fate of lower bulge/hair germ stem cells. This ultimately led to loss of proliferative potential, stem cell exhaustion, alopecia, and premature aging. Inactivation of aPKCλ produced more asymmetric divisions in different compartments, including the bulge. Thus, aPKCλ is crucial for homeostasis of self-renewing stratifying epithelia, and for the regulation of cell fate, differentiation, and maintenance of epidermal bulge stem cells likely through its role in balancing symmetric and asymmetric division.

scholarly journals Universality of clonal dynamics poses fundamental limits to identify stem cell self-renewal strategies

2020 ◽  
Author(s):  
Cristina Parigini ◽  
Philip Greulich
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Adult Stem Cells ◽  
Cell Lineage ◽  
Universality Class ◽  
Lineage Tracing ◽  
Self Renewal ◽  
Fundamental Limits ◽  
Challenges And Opportunities

How adult stem cells maintain self-renewing tissues is in vivo commonly assessed by analysing clonal data from cell lineage tracing assays. To identify strategies of stem cell self-renewal requires that different models of stem cell fate choice predict sufficiently different clonal statistics. Here we show that models of cell fate choice can, in homeostatic tissues, be categorized by exactly two ‘universality classes’, whereby models of the same class predict, under asymptotic conditions, the same clonal statistics. Those classes relate to generalizations of the canonical asymmetric vs. symmetric stem cell self-renewal strategies and are differentiated by a conservation law. This poses both challenges and opportunities to identify stem cell self-renewal strategies: while under asymptotic conditions, self-renewal models of the same universality class cannot be distinguished by clonal data only, models of different classes can be distinguished by simple means.

scholarly journals Universality of clonal dynamics poses fundamental limits to identify stem cell self-renewal strategies

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Cristina Parigini ◽  
Philip Greulich
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Adult Stem Cells ◽  
Cell Lineage ◽  
Universality Class ◽  
Lineage Tracing ◽  
Self Renewal ◽  
Fundamental Limits ◽  
Challenges And Opportunities

How adult stem cells maintain self-renewing tissues is commonly assessed by analysing clonal data from in vivo cell lineage-tracing assays. To identify strategies of stem cell self-renewal requires that different models of stem cell fate choice predict sufficiently different clonal statistics. Here, we show that models of cell fate choice can, in homeostatic tissues, be categorized by exactly two ‘universality classes’, whereby models of the same class predict, under asymptotic conditions, the same clonal statistics. Those classes relate to generalizations of the canonical asymmetric vs. symmetric stem cell self-renewal strategies and are distinguished by a conservation law. This poses both challenges and opportunities to identify stem cell self-renewal strategies: while under asymptotic conditions, self-renewal models of the same universality class cannot be distinguished by clonal data only, models of different classes can be distinguished by simple means.

scholarly journals Triple-cell lineage tracing by a dual reporter on a single allele

2019 ◽  
Vol 295 (3) ◽  
pp. 690-700 ◽  
Author(s):  
Kuo Liu ◽  
Muxue Tang ◽  
Hengwei Jin ◽  
Qiaozhen Liu ◽  
Lingjuan He ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Cell Function ◽  
Cell Lineage ◽  
Lineage Tracing ◽  
Cell Populations ◽  
Genetic Lineage ◽  
Traffic Light ◽  
Reporter System

Genetic lineage tracing is widely used to study organ development and tissue regeneration. Multicolor reporters are a powerful platform for simultaneously tracking discrete cell populations. Here, combining Dre-rox and Cre-loxP systems, we generated a new dual-recombinase reporter system, called Rosa26 traffic light reporter (R26-TLR), to monitor red, green, and yellow fluorescence. Using this new reporter system with the three distinct fluorescent reporters combined on one allele, we found that the readouts of the two recombinases Cre and Dre simultaneously reflect Cre+Dre−, Cre−Dre+, and Cre+Dre+ cell lineages. As proof of principle, we show specific labeling in three distinct progenitor/stem cell populations, including club cells, AT2 cells, and bronchoalveolar stem cells, in Sftpc-DreER;Scgb1a1-CreER;R26-TLR mice. By using this new dual-recombinase reporter system, we simultaneously traced the cell fate of these three distinct cell populations during lung repair and regeneration, providing a more comprehensive picture of stem cell function in distal airway repair and regeneration. We propose that this new reporter system will advance developmental and regenerative research by facilitating a more sophisticated genetic approach to studying in vivo cell fate plasticity.

scholarly journals Potential roles of stem cell marker genes in axon regeneration

2021 ◽  
Vol 53 (1) ◽  
pp. 1-7
Author(s):  
Jinyoung Lee ◽  
Yongcheol Cho
Keyword(s):  
Stem Cell ◽  
Expression Profiling ◽  
Axon Regeneration ◽  
Stem Cell Marker ◽  
Marker Genes ◽  
Cell Marker ◽  
Regenerative Capacity ◽  
Regeneration Mechanism ◽  
Central Nervous Systems

AbstractAxon regeneration is orchestrated by many genes that are differentially expressed in response to injury. Through a comparative analysis of gene expression profiling, injury-responsive genes that are potential targets for understanding the mechanisms underlying regeneration have been revealed. As the efficiency of axon regeneration in both the peripheral and central nervous systems can be manipulated, we suggest that identifying regeneration-associated genes is a promising approach for developing therapeutic applications in vivo. Here, we review the possible roles of stem cell marker- or stemness-related genes in axon regeneration to gain a better understanding of the regeneration mechanism and to identify targets that can enhance regenerative capacity.

scholarly journals Stiffness Gradients Mimicking In Vivo Tissue Variation Regulate Mesenchymal Stem Cell Fate

PLoS ONE ◽  
2011 ◽  
Vol 6 (1) ◽  
pp. e15978 ◽  
Author(s):  
Justin R. Tse ◽  
Adam J. Engler
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Fate ◽  
Stem Cell Fate

scholarly journals Characterization of histone inheritance patterns in the Drosophila female germline

2020 ◽  
Author(s):  
Elizabeth W. Kahney ◽  
Lydia Sohn ◽  
Kayla Viets-Layng ◽  
Robert Johnston ◽  
Xin Chen
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Single Gene ◽  
Asymmetric Division ◽  
Germline Stem Cell ◽  
Inheritance Patterns ◽  
Daughter Cells ◽  
Dividing Cells ◽  
Female Germline

ABSTRACTStem cells have the unique ability to undergo asymmetric division which produces two daughter cells that are genetically identical, but commit to different cell fates. The loss of this balanced asymmetric outcome can lead to many diseases, including cancer and tissue dystrophy. Understanding this tightly regulated process is crucial in developing methods to treat these abnormalities. Here, we report that produced from a Drosophila female germline stem cell asymmetric division, the two daughter cells differentially inherit histones at key genes related to either maintaining the stem cell state or promoting differentiation, but not at constitutively active or silenced genes. We combined histone labeling with DNA Oligopaints to distinguish old versus new histone distribution and visualize their inheritance patterns at single-gene resolution in asymmetrically dividing cells in vivo. This strategy can be widely applied to other biological contexts involving cell fate establishment during development or tissue homeostasis in multicellular organisms.

scholarly journals A novel Axin2 knock-in mouse model for visualization and lineage tracing of WNT/CTNNB1 responsive cells

2020 ◽  
Author(s):  
Anoeska Agatha Alida van de Moosdijk ◽  
Yorick Bernardus Cornelis van de Grift ◽  
Saskia Madelon Ada de Man ◽  
Amber Lisanne Zeeman ◽  
Renée van Amerongen
Keyword(s):  
Cell Fate ◽  
Mouse Strain ◽  
Critical Role ◽  
Lineage Tracing ◽  
Fluorescent Reporter ◽  
Cell Fate Decisions ◽  
Stem Cell Maintenance ◽  
Signaling Dynamics ◽  
Before And After

AbstractWnt signal transduction controls tissue morphogenesis, maintenance and regeneration in all multicellular animals. In mammals, the WNT/CTNNB1 (Wnt/β-catenin) pathway controls cell proliferation and cell fate decisions before and after birth. It plays a critical role at multiple stages of embryonic development, but also governs stem cell maintenance and homeostasis in adult tissues. However, it remains challenging to monitor endogenous WNT/CTNNB1 signaling dynamics in vivo. Here we report the generation and characterization of a new knock-in mouse strain that doubles as a fluorescent reporter and lineage tracing driver for WNT/CTNNB1 responsive cells. We introduced a multi-cistronic targeting cassette at the 3’ end of the universal WNT/CTNNB1 target gene Axin2. The resulting knock-in allele expresses a bright fluorescent reporter (3xNLS-SGFP2) and a doxycycline-inducible driver for lineage tracing (rtTA3). We show that the Axin2P2A-rtTA3-T2A-3xNLS-SGFP2 strain labels WNT/CTNNB1 cells at multiple anatomical sites during different stages of embryonic and postnatal development. It faithfully reports the subtle and dynamic changes in physiological WNT/CTNNB1 signaling activity that occur in vivo. We expect this mouse strain to be a useful resource for biologists who want to track and trace the location and developmental fate of WNT/CTNNB1 responsive stem cells in different contexts.Abstract Figure

Keratin 19 as a Stem Cell Marker In Vivo and In Vitro

2004 ◽  
pp. 103-110 ◽  
Author(s):  
Danielle Larouche ◽  
Cindy Hayward ◽  
Kristine Cuffley ◽  
Lucie Germain
Keyword(s):  
Stem Cell ◽  
Stem Cell Marker ◽  
Cell Marker ◽  
Keratin 19

Directing Stem Cell Fate in 3D Through Cell Inert and Adhesive Diblock Copolymer Domains

2013 ◽  
Author(s):  
Somyot Chirasatitsin ◽  
Priyalakshmi Viswanathan ◽  
Giuseppe Battaglia ◽  
Adam J. Engler
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Cell Adhesion ◽  
Cell Fate ◽  
Diblock Copolymer ◽  
Stem Cell Differentiation ◽  
Stem Cell Fate ◽  
Cell Behaviors ◽  
Cell Structures

Adhesions are important cell structures required to transduce a variety of chemical and mechanics signals from outside-in and vice versa, all of which regulate cell behaviors, including stem cell differentiation (1). Though most biomaterials are coated with an adhesive ligand to promote adhesion, they do not often have a uniform distribution that does not match the heterogeneously adhesive extracellular matrix (ECM) in vivo (2). We have previously shown that diblock copolymer (DBC) mixtures undergo interface-confined de-mixing to form nanodomins of one copolymer in another (3). Here we demonstrate how diblock copolymer mixtures can be made into foams with nanodomains to better recapitulate native ECM adhesion regions and influence cell adhesion.

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