Objective: To explore the role of sonic hedgehog (Shh) pathway in regulating the proliferation, migration and differentiation of hemangioblasts derived from aorta-gonad-mesonephros (AGM).
Methods: The hemangioblasts were isolated from AGM region of 11-day postcoitum (dpc) murine embryos by using the immuno-magnetic with CD34 and Flk1 monoclonal antibodies. The phenotypic analysis of hemangioblasts and AGM-derived stromal cells were detected by flow cytometry. The secretion of Shh was examined by immunohistochemical staining. The roles of Shh in regulating the proliferation, migration and differentiation of hemangioblasts in the transwell non-contact coculture system with AGM-derived stromal cells were observed by adding exogenous Shh N-Terminus and its antibody.
Results: The protein of Shh was highly expressed on AGM-derived stromal cells. The proliferation of hemangioblasts was promoted when co-cultured with AGM-derived stromal cells, and the effects of the latter could be blocked by antibody of Shh. The proliferation of hemangioblasts was strengthened further and kept for a long time without differentiation and apoptosis when exogenous Shh N-Terminus was added into the transwell non-contact co-culture system with AGM-derived stromal cells. When exogenous Shh N-Terminus was added into the cultural supernatant of hemangioblasts without AGM-derived stromal cells, the hemangioblasts were observed to be induced to apoptosis or differentiation after a short time of proliferation. Furthermore, the ability of migration could be promoted in the co-cultured hemangioblasts by adding exogenous Shh N-Terminus.
Conclusion: Shh pathway probably involves in the regulation of the proliferation, differentiation, apoptosis and migration of hemangioblasts, and is regulated by the AGM microenvironment.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Gata3 targets Runx1 in the embryonic haematopoietic stem cell niche.
IUBMB Life
January 2020
MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.
Runx1 is an important haematopoietic transcription factor as stressed by its involvement in a number of haematological malignancies. Furthermore, it is a key regulator of the emergence of the first haematopoietic stem cells (HSCs) during development. The transcription factor Gata3 has also been linked to haematological disease and was shown to promote HSC production in the embryo by inducing the secretion of important niche factors.
View Article and Find Full Text PDFHematopoietic stem cells (HSCs) first emerge during embryonic development within vessels such as the dorsal aorta of the aorta-gonad-mesonephros (AGM) region, suggesting that signals from the vascular microenvironment are critical for HSC development. Here, we demonstrated that AGM-derived endothelial cells (ECs) engineered to constitutively express AKT (AGM AKT-ECs) can provide an in vitro niche that recapitulates embryonic HSC specification and amplification. Specifically, nonengrafting embryonic precursors, including the VE-cadherin-expressing population that lacks hematopoietic surface markers, cocultured with AGM AKT-ECs specified into long-term, adult-engrafting HSCs, establishing that a vascular niche is sufficient to induce the endothelial-to-HSC transition in vitro.
View Article and Find Full Text PDFMaintenance of HSC by Wnt5a secreting AGM-derived stromal cell line.
Exp Hematol
January 2011
Stem Cell Institute, Katholieke Universiteit Leuven, Leuven, Belgium.
Objective: The microenvironment wherein hematopoietic stem cells (HSC) reside orchestrates HSC self-renewal vs. differentiation decisions. Stromal cells derived from ontogenically divergent hematopoietic microenvironments can support HSC in vitro and have been used to decipher factors that influence HSC fate decisions.
View Article and Find Full Text PDFInduction of hematopoietic differentiation of mouse embryonic stem cells by an AGM-derived stromal cell line is not further enhanced by overexpression of HOXB4.
Stem Cells Dev
November 2010
MRC Centre for Regenerative Medicine, John Hughes Bennett Laboratory, Queens Medical Research Institute, Edinburgh, United Kingdom.
Hematopoietic differentiation of embryonic stem (ES) cells can be enhanced by co-culture with stromal cells derived from hematopoietic tissues and by overexpression of the transcription factor HOXB4. In this study, we compare the hematopoietic inductive effects of stromal cell lines derived from different subregions of the embryonic aorta-gonad-mesonephros tissue with the commonly used OP9 stromal cell line and with HOXB4 activation. We show that stromal cell lines derived from the aorta and surrounding mesenchyme (AM) act at an earlier stage of the differentiation process compared with the commonly used OP9 stromal cells.
View Article and Find Full Text PDF[Biological characteristics of hematopoietic progenitor cells at different stages of hematopoietic development].
Sheng Li Xue Bao
October 2009
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
The aim of the present paper is to better understand the mechanism of hematopoietic development through studying the biological characteristics of hematopoietic progenitor cells at different stages of development. Firstly, the c-kit expression levels of the mononuclear cells from murine embryonic aorta-gonad-mesonephros (AGM) region at embryonic day (E)10.5 and E11.
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!