Objectives: Vitronectin (VTN) has been widely used for the maintenance and expansion of human pluripotent stem cells (hPSCs) as feeder-free conditions. However, the effect of VTN on hPSC differentiation remains unclear. Here, we investigated the role of VTN in early haematopoietic development of hPSCs.
Materials And Methods: A chemically defined monolayer system was applied to study the role of different matrix or basement membrane proteins in haematopoietic development of hPSCs. The role of integrin signalling in VTN-mediated haematopoietic differentiation was investigated by integrin antagonists. Finally, small interfering RNA was used to knock down integrin gene expression in differentiated cells.
Results: We found that the haematopoietic differentiation of hPSCs on VTN was far more efficient than that on Matrigel that is also often used for hPSC culture. VTN promoted the fate determination of endothelial-haematopoietic lineage during mesoderm development to generate haemogenic endothelium (HE). Moreover, we demonstrated that the signals through αvβ3 and αvβ5 integrins were required for VTN-promoted haematopoietic differentiation. Blocking αvβ3 and αvβ5 integrins by the integrin antagonists impaired the development of HE, but not endothelial-to-haematopoietic transition (EHT). Finally, both αvβ3 and αvβ5 were confirmed acting synergistically for early haematopoietic differentiation by knockdown the expression of αv, β3 or β5.
Conclusion: The established VTN-based monolayer system of haematopoietic differentiation of hPSCs presents a valuable platform for further investigating niche signals involved in human haematopoietic development.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016644 | PMC |
| http://dx.doi.org/10.1111/cpr.13012 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Oncogenic role of RARG rearrangements in acute myeloid leukemia resembling acute promyelocytic leukemia.
Nat Commun
January 2025
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Acute myeloid leukemia (AML) featuring retinoic acid receptor-gamma (RARG) rearrangements exhibits morphological features resembling those of acute promyelocytic leukemia but is associated with drug resistance and poor clinical outcomes. However, the mechanisms underlying the role of RARG fusions in leukemogenesis remain elusive. Here, we show that RARG fusions disrupt myeloid differentiation and promote proliferation and self-renewal of hematopoietic stem and progenitor cells (HSPCs) by upregulating BCL2 and ATF3.
View Article and Find Full Text PDFOsterix mRNA Enrichment in Small Extracellular Vesicles Derived From Osteogenically Induced ADSCs: A Promoter of Osteogenic Differentiation in BMSCs.
J Cell Mol Med
January 2025
Department of Spine, Orthopaedic Center, Guangdong Second Provincial General Hospital, Jinan University, Guangzhou, China.
Osteogenic differentiation of bone marrow stem cells (BMSCs) is essential for bone tissue regeneration and repair. However, this process is often hindered by an unstable differentiation influenced by local microenvironmental factors. While small extracellular vesicles (sEVs) derived from osteogenically induced adipose mesenchymal stem cells (ADSCs) reportedly can promote osteogenic differentiation of BMSCs, the underlying molecular mechanisms remain incompletely understood.
View Article and Find Full Text PDFRegenerative properties of bone marrow mesenchymal stem cell derived exosomes in rotator cuff tears.
J Transl Med
January 2025
Department of Joint Surgery, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.
Rotator cuff injury (RCI), characterized by shoulder pain and restricted mobility, represents a subset of tendon-bone insertion injuries (TBI). In the majority of cases, surgical reconstruction of the affected tendons or ligaments is required to address the damage. However, numerous clinical failures have underscored the suboptimal outcomes associated with such procedures.
View Article and Find Full Text PDFThe diagnostic value and clinical correlations of bone marrow supernatant S100A8 and S100A9 in myelodysplastic neoplasms.
Cytokine
January 2025
Department of Hematology and Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China. Electronic address:
Purpose: Myelodysplastic neoplasms (MDS) are heterogeneous neoplasms that originate from bone marrow (BM) hematopoietic stem cells. S100A8 and S100A9 (S100A8/9) are crucial molecules involved in the innate immune pathogenesis of MDS. This study aimed to explore the value of these molecules in the differential diagnosis of MDS, and analyze the correlations between their concentrations and clinical characteristics.
View Article and Find Full Text PDFProtocol for differentiating hematopoietic progenitor cells from human pluripotent stem cells in chemically defined monolayer culture.
STAR Protoc
January 2025
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China. Electronic address:
Human pluripotent stem cells (hPSCs) provide a powerful platform for generating hematopoietic progenitor cells (HPCs) and investigating hematopoietic development. Here, we present a protocol for maintaining hPSCs and inducing their differentiation into HPCs through the endothelial-to-hematopoietic transition (EHT) on vitronectin-coated plates. We outline steps for evaluating the efficiency of HPC generation and assessing their potential to differentiate into various hematopoietic lineages.
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!