Extracellular vesicles(EVs)are tiny biological nanovesicles ranging from approximately 30–1000 nm in diameter that are released into the extracellular matrix of most cell types and in biofluids.The classification of ...Extracellular vesicles(EVs)are tiny biological nanovesicles ranging from approximately 30–1000 nm in diameter that are released into the extracellular matrix of most cell types and in biofluids.The classification of EVs includes exosomes,microvesicles,and apoptotic bodies,dependent on various factors such as size,markers,and biogenesis pathways.The transition of EV relevance from that of being assumed as a trash bag to be a key player in critical physiological and pathological conditions has been revolutionary in many ways.EVs have been recently revealed to play a crucial role in stem cell biology and cancer progression via intercellular communication,contributing to organ development and the progression of cancer.This review focuses on the significant research progress made so far in the role of the crosstalk between EVs and stem cells and their niche,and cellular communication among different germ layers in developmental biology.In addition,it discusses the role of EVs in cancer progression and their application as therapeutic agents or drug delivery vehicles.All such discoveries have been facilitated by tremendous technological advancements in EV-associated research,especially the microfluidics systems.Their pros and cons in the context of characterization of EVs are also extensively discussed in this review.This review also deliberates the role of EVs in normal cell processes and disease conditions,and their application as a diagnostic and therapeutic tool.Finally,we propose future perspectives for EV-related research in stem cell and cancer biology.展开更多
A major unanswered question is how a TCR discriminates between foreign and self-peptides presented on the APC surface.Here,we used in situ fluorescence resonance energy transfer(FRET)to measure the distances of single...A major unanswered question is how a TCR discriminates between foreign and self-peptides presented on the APC surface.Here,we used in situ fluorescence resonance energy transfer(FRET)to measure the distances of single TCR–pMHC bonds and the conformations of individual TCR–CD3ζreceptors at the membranes of live primary T cells.We found that a TCR discriminates between closely related peptides by forming single TCR–pMHC bonds with different conformations,and the most potent pMHC forms the shortest bond.The bond conformation is an intrinsic property that is independent of the binding affinity and kinetics,TCR microcluster formation,and CD4 binding.The bond conformation dictates the degree of CD3ζdissociation from the inner leaflet of the plasma membrane via a positive calcium signaling feedback loop to precisely control the accessibility of CD3ζITAMs for phosphorylation.Our data revealed the mechanism by which a TCR deciphers the structural differences among peptides via the TCR–pMHC bond conformation.展开更多
基金U.S.National Institute of Health(4R00CA226353-02 to H J.Chen)Hong Kong Health and Medical Research Fund(HMRF:No.:06172956 to Q.L)+1 种基金Stem Cell and Regenerative Medicine Fund(Guangzhou Women and Children’s Medical Centre,Grant No.:5001-4001010 to Q.L)Research Grants Council Theme-based Research Scheme(TRS:No.T12-703-19R to Q.L.).
文摘Extracellular vesicles(EVs)are tiny biological nanovesicles ranging from approximately 30–1000 nm in diameter that are released into the extracellular matrix of most cell types and in biofluids.The classification of EVs includes exosomes,microvesicles,and apoptotic bodies,dependent on various factors such as size,markers,and biogenesis pathways.The transition of EV relevance from that of being assumed as a trash bag to be a key player in critical physiological and pathological conditions has been revolutionary in many ways.EVs have been recently revealed to play a crucial role in stem cell biology and cancer progression via intercellular communication,contributing to organ development and the progression of cancer.This review focuses on the significant research progress made so far in the role of the crosstalk between EVs and stem cells and their niche,and cellular communication among different germ layers in developmental biology.In addition,it discusses the role of EVs in cancer progression and their application as therapeutic agents or drug delivery vehicles.All such discoveries have been facilitated by tremendous technological advancements in EV-associated research,especially the microfluidics systems.Their pros and cons in the context of characterization of EVs are also extensively discussed in this review.This review also deliberates the role of EVs in normal cell processes and disease conditions,and their application as a diagnostic and therapeutic tool.Finally,we propose future perspectives for EV-related research in stem cell and cancer biology.
基金This work was mainly supported by NIH grants R00AI106941 and R21AI120010NSF CAREER Award 1653782,a Chicago Biomedical Consortium Catalyst Award(to J.H.)+1 种基金postdoctoral grant PDR-092(to D.K.S.),with additional support from the Searle Funds at The Chicago Community TrustThis work is also supported by NIH grant R01AI126756(to E.J.A.)and R01CA022677(to H.S.).
文摘A major unanswered question is how a TCR discriminates between foreign and self-peptides presented on the APC surface.Here,we used in situ fluorescence resonance energy transfer(FRET)to measure the distances of single TCR–pMHC bonds and the conformations of individual TCR–CD3ζreceptors at the membranes of live primary T cells.We found that a TCR discriminates between closely related peptides by forming single TCR–pMHC bonds with different conformations,and the most potent pMHC forms the shortest bond.The bond conformation is an intrinsic property that is independent of the binding affinity and kinetics,TCR microcluster formation,and CD4 binding.The bond conformation dictates the degree of CD3ζdissociation from the inner leaflet of the plasma membrane via a positive calcium signaling feedback loop to precisely control the accessibility of CD3ζITAMs for phosphorylation.Our data revealed the mechanism by which a TCR deciphers the structural differences among peptides via the TCR–pMHC bond conformation.
