Interruption of Klf5 acetylation in basal progenitor cells promotes luminal commitment by activating Notch signaling

2021 ◽  
Author(s):  
Baotong Zhang ◽  
Siyuan Xia ◽  
Mingcheng Liu ◽  
Xiawei Li ◽  
Shimin Shuai ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Progenitor Cells ◽  
Basal Progenitor

Ablation of cdk4 and cdk6 affects proliferation of basal progenitor cells in the developing dorsal and ventral forebrain

2018 ◽  
Vol 78 (7) ◽  
pp. 660-670 ◽  
Author(s):  
Alice Grison ◽  
Carine Gaiser ◽  
Andrea Bieder ◽  
Constanze Baranek ◽  
Suzana Atanasoski
Keyword(s):  
Progenitor Cells ◽  
Basal Progenitor

scholarly journals HIV induces airway basal progenitor cells to adopt an inflammatory phenotype

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nancy P. Y. Chung ◽  
K. M. Faisal Khan ◽  
Robert J. Kaner ◽  
Sarah L. O’Beirne ◽  
Ronald G. Crystal
Keyword(s):  
Progenitor Cells ◽  
Inflammatory Mediators ◽  
Lung Inflammation ◽  
Mapk Signaling ◽  
Gm Csf ◽  
Basal Progenitor ◽  
Inflammatory Phenotype ◽  
Mapk Signaling Pathways ◽  
Chronic Hiv Infection

AbstractDespite the introduction of anti-retroviral therapy, chronic HIV infection is associated with an increased incidence of other comorbidities such as COPD. Based on the knowledge that binding of HIV to human airway basal stem/progenitor cells (BC) induces a destructive phenotype by increased MMP-9 expression through MAPK signaling pathways, we hypothesized that HIV induces the BC to express inflammatory mediators that contribute to the pathogenesis of emphysema. Our data demonstrate that airway BC isolated from HAART-treated HIV+ nonsmokers spontaneously release inflammatory mediators IL-8, IL-1β, ICAM-1 and GM-CSF. Similarly, exposure of normal BC to HIV in vitro up-regulates expression of the same inflammatory mediators. These HIV-BC derived mediators induce migration of alveolar macrophages (AM) and neutrophils and stimulate AM proliferation. This HIV-induced inflammatory phenotype likely contributes to lung inflammation in HIV+ individuals and provides explanation for the increased incidence of COPD in HIV+ individuals.

scholarly journals Ex vivo expansion of human hematopoietic stem and progenitor cells

Blood ◽  
2011 ◽  
Vol 117 (23) ◽  
pp. 6083-6090 ◽  
Author(s):  
Ann Dahlberg ◽  
Colleen Delaney ◽  
Irwin D. Bernstein
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Notch Signaling ◽  
Progenitor Cells ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Hematopoietic Growth Factors ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

AbstractDespite progress in our understanding of the growth factors that support the progressive maturation of the various cell lineages of the hematopoietic system, less is known about factors that govern the self-renewal of hematopoietic stem and progenitor cells (HSPCs), and our ability to expand human HSPC numbers ex vivo remains limited. Interest in stem cell expansion has been heightened by the increasing importance of HSCs in the treatment of both malignant and nonmalignant diseases, as well as their use in gene therapy. To date, most attempts to ex vivo expand HSPCs have used hematopoietic growth factors but have not achieved clinically relevant effects. More recent approaches, including our studies in which activation of the Notch signaling pathway has enabled a clinically relevant ex vivo expansion of HSPCs, have led to renewed interest in this arena. Here we briefly review early attempts at ex vivo expansion by cytokine stimulation followed by an examination of our studies investigating the role of Notch signaling in HSPC self-renewal. We will also review other recently developed approaches for ex vivo expansion, primarily focused on the more extensively studied cord blood–derived stem cell. Finally, we discuss some of the challenges still facing this field.

Basal progenitor cells bridge the development, malignant cancers, and multiple diseases of esophagus

2017 ◽  
Vol 233 (5) ◽  
pp. 3855-3866
Author(s):  
Baoshun Lin ◽  
Fuan Xie ◽  
Zhangwu Xiao ◽  
Xiaoqian Hong ◽  
Liming Tian ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Basal Progenitor

Abstract 212: Aggregation of Child Cardiac Progenitor Cells into 3D Spheres Improves Endothelial Lineage Commitment

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
David Q Trac ◽  
Chunhui Xu ◽  
Michael E. Davis
Keyword(s):  
Stem Cell ◽  
Cardiac Function ◽  
Notch Signaling ◽  
Progenitor Cells ◽  
Gene Array ◽  
Lineage Commitment ◽  
Cardiac Progenitor Cells ◽  
Notch Ligand ◽  
Monolayer Cultures ◽  
Endothelial Lineage

Congenital heart disease is rarely cured by surgery and can lead to life-threatening, intractable right ventricular heart failure (HF). In particular, children with hypoplastic left heart syndrome have a 10 year transplant-free survival rate of 50-75% despite palliative surgical repair. Currently, no effective stem-cell based treatments are available for pediatric HF. Recent stem-cell based clinical trials have been limited by poor differentiation rates and low cell retention. Additionally, we have shown that human cardiac progenitor cells (hCPCs) have reduced regenerative potential as they age, starting as early as 1 year old. We propose the aggregation of CPCs into scaffold-free spheres to improve the differentiation of child CPCs into mature cardiac phenotypes by enhancing intercellular Notch signaling. Notch signaling activity has been implicated in the regulation of CPC fate decisions and prior research in our lab has shown that intramyocardial delivery of Notch-ligand containing hydrogels improves cardiac function. Child CPC spheres were produced at a size of 1500 cells per sphere using a microwell array and cultured in suspension. Using immunohistochemistry, we showed that aggregation of CPCs increased Notch1 expression compared to parallel monolayer cultures. This effect is not limited to CPCs and was recapitulated in spheres of Chinese hamster ovarian cells transfected with Notch1-YFP. Additionally, Notch signaling pathway gene array data showed increased expression of the Notch-cleaving metalloprotease ADAM10 (3.6-fold) and Notch ligand DLL1 (25.0-fold) in CPC spheres by 3 days in culture compared to monolayer cultures. By 14 days in culture, we showed that aggregation of CPCs robustly increases the expression of the GATA4, a cardiac transcription factor associated with angiogenesis, and VEGFR1, an early marker of endothelial lineage commitment. Based on our results, we hypothesize that aggregation of CPCs into spheroids increases endothelial differentiation via a Notch-dependent mechanism. Transplantation of CPC spheres may improve cardiac function in vivo compared to transplantation of single CPCs. The results from our project will facilitate the development of autologous stem-cell based therapies for pediatric HF.

scholarly journals Aggregation of Child Cardiac Progenitor Cells Into Spheres Activates Notch Signaling and Improves Treatment of Right Ventricular Heart Failure

2019 ◽  
Vol 124 (4) ◽  
pp. 526-538 ◽  
Author(s):  
David Trac ◽  
Joshua T. Maxwell ◽  
Milton E. Brown ◽  
Chunhui Xu ◽  
Michael E. Davis
Keyword(s):  
Heart Failure ◽  
Right Ventricular ◽  
Notch Signaling ◽  
Progenitor Cells ◽  
Cardiac Progenitor Cells

scholarly journals Notch Inhibition Promotes Differentiation of Liver Progenitor Cells into Hepatocytes via sox9b Repression in Zebrafish

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jacquelyn O. Russell ◽  
Sungjin Ko ◽  
Satdarshan P. Monga ◽  
Donghun Shin
Keyword(s):  
Liver Disease ◽  
Liver Regeneration ◽  
Notch Signaling ◽  
Chronic Liver Disease ◽  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Therapeutic Option ◽  
Chronic Liver ◽  
Hepatocyte Proliferation ◽  
Hepatocyte Differentiation

Liver regeneration after most forms of injury is mediated through the proliferation of hepatocytes. However, when hepatocyte proliferation is impaired, such as during chronic liver disease, liver progenitor cells (LPCs) arising from the biliary epithelial cell (BEC) compartment can give rise to hepatocytes to mediate hepatic repair. Promotion of LPC-to-hepatocyte differentiation in patients with chronic liver disease could serve as a potentially new therapeutic option, but first requires the identification of the molecular mechanisms driving this process. Notch signaling has been identified as an important signaling pathway promoting the BEC fate during development and has also been implicated in regulating LPC differentiation during regeneration. SRY-related HMG box transcription factor 9 (Sox9) is a direct target of Notch signaling in the liver, and Sox9 has also been shown to promote the BEC fate during development. We have recently shown in a zebrafish model of LPC-driven liver regeneration that inhibition of Hdac1 activity through MS-275 treatment enhances sox9b expression in LPCs and impairs LPC-to-hepatocyte differentiation. Therefore, we hypothesized that inhibition of Notch signaling would promote LPC-to-hepatocyte differentiation by repressing sox9b expression in zebrafish. We ablated the hepatocytes of Tg(fabp10a:CFP-NTR) larvae and blocked Notch activation during liver regeneration through treatment with γ-secretase inhibitor LY411575 and demonstrated enhanced induction of Hnf4a in LPCs. Alternatively, enhancing Notch signaling via Notch3 intracellular domain (N3ICD) overexpression impaired Hnf4a induction. Hepatocyte ablation in sox9b heterozygous mutant embryos enhanced Hnf4a induction, while BEC-specific Sox9b overexpression impaired LPC-to-hepatocyte differentiation. Our results establish the Notch-Sox9b signaling axis as inhibitory to LPC-to-hepatocyte differentiation in a well-established in vivo LPC-driven liver regeneration model.

scholarly journals Human Cytomegalovirus Infection Dysregulates the Localization and Stability of NICD1 and Jag1 in Neural Progenitor Cells

2015 ◽  
Vol 89 (13) ◽  
pp. 6792-6804 ◽  
Author(s):  
Xiao-Jun Li ◽  
Xi-Juan Liu ◽  
Bo Yang ◽  
Ya-Ru Fu ◽  
Fei Zhao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Notch Signaling ◽  
Progenitor Cells ◽  
Human Cytomegalovirus ◽  
Neural Progenitor Cells ◽  
Hcmv Infection ◽  
Fetal Brain ◽  
Neural Progenitor ◽  
Notch Signaling Pathway ◽  
Protein Levels

ABSTRACTHuman cytomegalovirus (HCMV) infection of the developing fetus frequently results in major neural developmental damage. In previous studies, HCMV was shown to downregulate neural progenitor/stem cell (NPC) markers and induce abnormal differentiation. As Notch signaling plays a vital role in the maintenance of stem cell status and is a switch that governs NPC differentiation, the effect of HCMV infection on the Notch signaling pathway in NPCs was investigated. HCMV downregulated mRNA levels of Notch1 and its ligand, Jag1, and reduced protein levels and altered the intracellular localization of Jag1 and the intracellular effector form of Notch1, NICD1. These effects required HCMV gene expression and appeared to be mediated through enhanced proteasomal degradation. Transient expression of the viral tegument proteins of pp71 and UL26 reduced NICD1 and Jag1 protein levels endogenously and exogenously. Given the critical role of Notch signaling in NPC growth and differentiation, these findings reveal important mechanisms by which HCMV disturbs neural cell developmentin vitro. Similar eventsin vivomay be associated with HCMV-mediated neuropathogenesis during congenital infection in the fetal brain.IMPORTANCECongenital human cytomegalovirus (HCMV) infection is the leading cause of birth defects that primarily manifest as neurological disabilities. Neural progenitor cells (NPCs), key players in fetal brain development, are the most susceptible cell type for HCMV infection in the fetal brain. Studies have shown that NPCs are fully permissive for HCMV infection, which causes neural cell loss and premature differentiation, thereby perturbing NPC fate. Elucidation of virus-host interactions that govern NPC proliferation and differentiation is critical to understanding neuropathogenesis. The Notch signaling pathway is critical for maintaining stem cell status and functions as a switch for differentiation of NPCs. Our investigation into the impact of HCMV infection on this pathway revealed that HCMV dysregulates Notch signaling by altering expression of the Notch ligand Jag1, Notch1, and its active effector in NPCs. These results suggest a mechanism for the neuropathogenesis induced by HCMV infection that includes altered NPC differentiation and proliferation.

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