To explore the role of PDK1 in the transition of endothelial to hematopoietic cells and its effect on the generation and normal function of HSC. PDK1 was deleted specifically in endothelial cells expressing VEC (Vascular Endothelial Cadherin). CFU-C was performed to detect the effect of PDK1 on the function of hematopoietic progenitor cells using the cells from PDK1(fl/fl), PDK1(fl/+) and Vec-Cre; PDK1(fl/fl) AGM region. Hematopoietic stem cell transplantation assay was conducted to determine the effect of PDK1 on hematopoietic stem cells. Flow cytometry was performed to analyze the influence of PDK1 on percentage, cell cycle and apoptosis of CD31(+)c-Kit(high) cell population. Real-time PCR was conducted to measure the expression of transcription factors involved in process of transition from endothelial to hematopoietic cells. In contrast to the wild type group, the CFU from PDK1-deficient hematopoietic progenitor cells showed smaller in morphology and fewer in quantity. CFU-GM was (24±5)/ee in knockout group, and the control group was (62±1)/ee (=0.001). PDK1 deletion severely impaired the ability to repopulate hematopoietic cells and differentiate into committed cells. hematopoietic progenitor cells from knockout group was transplanted into 5 recipients without any recipients reconstructed. However, 5 of 7 recipients were reconstructed in control group (=0.001). The proportion of intra-vascular clusters in the AGM was decreased (the frequency of CD31(+)c-Kit(high) in the knockout group was (0.145±0.017)%, and the control group ratio was (0.385±0.040)% (=0.001), but not due to the inhibition of cell proliferation and/or increase of apoptosis. Further study found that the absence of endothelial PDK1 causes a decreased expression of RUNX1, P2-RUNX1, GATA2 and other important hematopoietic-related transcription factors in hemogenic cluster. PDK1 deletion impairs the transition of endothelial cells to hematopoietic cells as well as the generation and function of HSC.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342253 | PMC |
| http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2018.09.002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Bacteria in hypertrophic scars promote scar formation through HSBP1-mediated autophagy.
Wound Repair Regen
January 2025
Department of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Bacterial colonisation in hypertrophic scars (HSs) has been reported, yet the precise mechanism of their contribution to scar formation remains elusive. To address this, we examined HS and normal skin (NS) tissues through Gram staining and immunofluorescence. We co-cultured fibroblasts with heat-inactivated Staphylococcus aureus (S.
View Article and Find Full Text PDFCholangiocyte-derived exosomal long noncoding RNA PICALM-AU1 promotes pulmonary endothelial cell endothelial-mesenchymal transition in hepatopulmonary syndrome.
Heliyon
February 2024
Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
Hepatopulmonary syndrome (HPS) is a severe lung injury caused by chronic liver disease, with limited understanding of the disease pathology. Exosomes are important mediators of intercellular communication that modulates various cellular functions by transferring a variety of intracellular components to target cells. Our recent studies have indicated that a new long noncoding RNA (lncRNA), PICALM-AU1, is mainly expressed in cholangiocytes, and is dramatically induced in the liver during HPS.
View Article and Find Full Text PDFThe Roles of Myeloid Cells in Breast Cancer Progression.
Adv Exp Med Biol
January 2025
Lester and Sue Smith Breast Center, Houston, TX, USA.
This chapter reviews tumor-associated myeloid cells, including macrophages, neutrophils, and other innate immune cells, and their multifaceted roles in supporting breast cancer progression and metastasis. In primary tumors, myeloid cells play key roles in promoting tumor epithelial-mesenchymal transition (EMT) and invasion. They can facilitate intravasation (entry into the bloodstream) and colonization, disrupting the endothelial cell layer and reshaping the extracellular matrix.
View Article and Find Full Text PDFPosterior Limbal Mesenchymal Stromal Cells Promote Proliferation and Stemness of Transition Zone Cells: A Novel Insight Into Corneal Endothelial Rejuvenation.
Invest Ophthalmol Vis Sci
January 2025
Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
Purpose: Progenitors for the corneal endothelium have been identified in the transition zone (TZ), but their cellular interactions remain undefined. Posterior limbal mesenchymal stromal cells (P-LMSCs) may support TZ cells in the posterior limbus. This study aims to characterize P-LMSCs and investigate their effects on TZ cells.
View Article and Find Full Text PDFEndothelial cell (EC)-specific CTGF/CCN2 Expression Increases EC Reprogramming and Atherosclerosis.
Matrix Biol
January 2025
Department of Surgery, Emory University, Atlanta, GA, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA; Research Services, Atlanta VA Medical Center, Decatur, GA, USA. Electronic address:
Arterial endothelial cells (ECs) reside in a complex biomechanical environment. ECs sense and respond to wall shear stress. Low and oscillatory wall shear stress is characteristic of disturbed flow and commonly found at arterial bifurcations and around atherosclerotic plaques.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!