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Bài trên là chi tiết về mô và quá trình giao tiếp giữa các tế bào phục vụ môn Sinh học tế bào ngành CNSH . Gap junction intercellular communication (GJIC) is ubiquitous in the majority of cells and is indispensable for proper development and function of most tissues. The loss of gap junction mediated cell to cell communication leads to compromised development in many tissues and organs, and also facilitates tumorigenesis and autonomous cell behavior in cancerous cells. Because cells embedded in an extracellular matrix constantly interact through gap junctions to coordinate normal tissue functions and homeostasis, our group hypothesized that increasing cell to cell communication, via genetically engineering cells to overexpress gap junction proteins, could improve cell signaling and increase differentiation in interior regions of engineered tissue equivalents. In a recent paper,1 we presented a platform to regenerate full 3D equivalents of engineered tissue, providing a strategy to overcome a barrier in regenerative medicine. These findings suggest that both targeted delivery and cellbased strategies can be used as treatments to enhance communication in 3D living tissue.2 In this addendum, we address the effects of extracellular calcium (Ca2+e) on intracellular calcium (Ca2+i), GJIC and osteogenic differentiation under conditions in which bone marrow stromal cells (BMSCs) also exhibit higher celltocell communication. As a key secondary messenger in many biological processes, the levels of Ca2+e and Ca2+i play a role in cell differentiation and may be a tunable signal in tissue regeneration. Higher celltocell communication was achieved by both genetically engineering cells to overexpress connexin 43 (Cx43) and by a high density cell seeding technique, denoted micromass seeding (MM). The results presented in this addendum show that the intensity and duration of a second messenger, like calcium, can be augmented in a platform that enables higher celltocell communication. The ability to modulate calcium signaling, combined with our previous approaches to modulate GJIC, may have an impact on tissue regeneration and therapies for communication incompetent cells, such as those associated with heart disease and certain types of cancer. Key words: connexin 43 (Cx43), gap junction intercellular communication (GJIC), calcium, micromass cultures, Bone
Mơ & Q trình giao tiếp tế bào Hồng Thanh Vân, PhD Các loại mơ thể người Mơ tập hợp nhóm tế bào thực chức Xương Da mô lớn thể Mô Hệ quan Cơ quan Cấu trúc ruột động vật có vú Biểu mô Mô liên kết Mô Mô liên kết Biểu mô Các mô https://www.youtube.com/watch?v=i5tR3csCWYo Growth (Tăng trưởng) Differentiation (Khả biệt hoá) Mềm suốt (như thủy tinh thể bên mắt) Anti-transformation into cancer (Chống lại hình thành khối u) Protection from infectious agents (Bảo vệ khỏi tác nhận lây nhiễm) Maintenance (Khả bảo trì) Tế bào, Dai đàn hồi Ma trận, (gân, hạ bì) Sợi Self repair (Sửa chữa) Regeneration (Tái sinh) Transformation (Chuyển dạng) Chống sốc (sụn) Preservation (Bảo quản) Cứng đặc (xương) Aging and death (Lão hóa chết) Các thành phần mơ Mô (TISSUE) Chất ngoại bào Liên kết tế bào (Cells – Cell junctions) (Extracellular matrix) Mô liên kết (Connective tissue) Mô thần kinh Biểu mô Mô (nervous tissue) (Epithelial tissue) (Muscle tissue) Các mô kết nối ma trận ngoại bào Các sợi ma trận ngoại bào 10 Liên kết chặt 32 Các liên kết gắn tế bào biểu mô với Epithelial Sheets and Cell Junctions với chất ngoại bào (lamina705đáy) oth built around transmemmily: a cadherin molecule in • an Liênidentical kết dính (Adherens ctly to cadherin liên kiết ghbor (junction) Figure 20–23 ) Such desmosome gắn tế bào hilic binding In the case of biểu mô với tế bào present in mô thekhác extracellular biểu • Các hemidesmosome gắn kết plasma membrane cytoskeletal filament Các liên kết nối với sợi khung xương tế bào tế bào chất Protein quan trọng loại liên kết cadherin cadherin linker olecule is tethered tế bào biểuinside mô vào its lớp protein proteins ments lamina Often,đáy the adherens CELL CELL around each of the interactthe apical end of the cell, Figure 20–23 Cadherin proteins mediate ) Bundles of actin filaments mechanical attachment of one cell to another Identical cadherin molecules in the he epithelium This network Tất tế bào biểu mơ kết nối mạng lưới thông qua sợi khung xương tế bào plasma membranes of adjacent cells bind ments and can thus liên kiết contract, 33 to each other extracellularly; inside the cell, velop tension and to change Liên kết dính actin filaments inside microvillus LUMEN • Các protein cadherin liên kết với sợi actin thơng qua số linker protein • Các liên kết dính nằm gần cực đỉnh tế bào, liên kết chặt (liên kêt vịng bịt) • Chúng thường tạo vịng kết dính liên tục bao quanh tế bào biểu mô microvilli extending from apical surface tight junction bundle of actin filaments adherens junction cadherins lateral plasma membranes of adjacent epithelial cells 10 µm 34 surface basal Siêu họ protein cadherin CELL–CELL JUNCTIONS cadherin Chapter 19:classical Cell Junctions and the Extracellular Matrix (E-cadherin) Fat cadherin 38.5 nm N Flamingo N Ret Ca2+ a ne desmocollin cadherin 23 1039 Figure 19–4 The cadherin superfamily The diagram shows some of the diversity among cadherin superfamily members These proteins all have extracellular portions containing multiple copies of the extracellular cadherin domain (green ovals) In the classical cadherins of vertebrates there are of these domains, and in desmogleins and desmocollins there are or 5, but some nonclassical cadherins have more than 30 The intracellular portions are more varied, reflecting interactions C with a wide variety of intracellular ligands, including signaling molecules and adaptor proteins that connect the cadherin to the cytoskeleton In some cases, such as T-cadherin, a transmembrane domain is not present and the protein is plasma attached to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor Ca2+ membrane The differently colored motifs in Fat, of cell Flamingo, and Ret represent conserved domains that are also found in other protein families Các phân tử canxi ổn định cấu trúc domain cadherin ngoại bào > mM Ca2+ Ca2+ < 0.05 mM Ca2+ cadherin domains protocadherins (Pcdh γ) flexible hinge region hinge regions N-terminal cadherin domains T-cadherin INTRACELLULAR plasma EXTRACELLULAR (B) Figure 19–6 Cadherin structure and function (A) The extracellular region of 35 Mọi thể sống phôi thai https://www.youtube.com/watch?v=dXpAbezdOho 36 706 Cell Communities: Tissues sheet of epithelial cells Sự hình thành ống biểu mơ munities: Tissues, Stem Cells, and Cancer CHAPTER 20 adhesion belt with associated actin filaments INVAGINATION OF EPITHELIAL SHEET CAUSED BY AN ORGANIZED TIGHTENING ALONG ADHESION BELTS IN SELECTED REGIONS OF CELL SHEET OF ET CAUSED ED ONG S IN SELECTED L SHEET E NG tube (B) 50 µm forming neural tube (C) forming retina of eye cup ( EPITHELIAL TUBE PINCHES OFF FROM OVERLYING SHEET OF CELLS 50 µm lens vesicle Figure 20–25 Epithelial sheets can bend to form an epithelial tube or vesicle Contraction of apical bundles of actin filaments linked from cell to cell via adherens junctions causes the epithelial cells to narrow at their apex Depending on whether the contraction of the epithelial sheet is oriented along one axis, or is equal in all directions, the epithelium will either roll up into a tube or invaginate to form a vesicle, respectively (A) Diagram showing how an apical contraction along one axis of an epithelial sheet can cause the sheet to form a tube (B) Scanning electron micrograph of a cross section through the trunk of a two-day chick embryo, showing the formation of the neural tube by the process shown in (A) Part of the epithelial epithelial tube (A) 37 different groups of cells segregate from one another according to the cadherins they express (Micrographs courtesy of Miwako neural tube Nomura and Masatoshi Takeichi.) crest cells detach from the neura (A, B) Immunofluorescence micro showing the developing neural tu with antibodies against (A) E-cad and (B) N-cadherin (yellow) (C) A patterns of gene expression chan different groups of cells segregate another according to the cadherin express (Micrographs courtesy o Nomura and Masatoshi Takeichi.) Biểu cadherin trình hình thành hệ thần kinh động vật có xương sống (B) cells expressing E-cadherin 50 µm 6B cells expressing cadherin cells expressing N-cadherin cells expressing cadherin (C) CELL–CELL JUNCTIONS dherin herin 6B dherin herin E-cadherin neural tube neural crest cells (B) (A) N-cadherin ectoderm 50 µm 1041 Figure 19–8 Changing patterns of cadherin expression during construction of the vertebrate nervous system The figure shows cross sections of the early chick embryo, as the neural tube detaches neural tube cells expressing E-cadherin from the ectoderm and then as neural crest cells from the neural tube cellsdetach expressing cadherin 6B MBoC6 m19.12/19.08 (A, B) cells Immunofluorescence micrographs expressing N-cadherin showing the developing neural tube labeled cells expressing cadherin with antibodies against (A) E-cadherin (blue) and (B) N-cadherin (yellow) (C) As the (C) patterns of gene expression change, the different groups of cells segregate from one another according to the cadherins they express (Micrographs courtesy of Miwako Nomura and Masatoshi Takeichi.) cell expressing E-cadherin Cadherins play a crucial part in these cell-sorting processes during developneural crest SORTING ment The appearance and disappearance of specific cadherins correlate with cells OUT neural crest steps in embryonic development where cells regroup and change their contacts cells to create new tissue structures In the vertebrate embryo, for example, changes in cadherin expression are seen when the neural tube forms and pinches off from cell expressing (A) N-cadherin the overlying ectoderm: neural tube cells Thí losenghiệm: E-cadherin and acquire other cad(A) (B) herins, including N-cadherin, while the cells in the overlying ectoderm continue 50 µm cell expressing cellwhen expressing cell expressing to express E-cadherin (Figure 19–8A and B) Then, the neural crest cells high level of E-cadherin E-cadherin E-cadherin migrate away from the neural tube, these cadherins become scarcely detectable, Cadherins play a crucial part in these cell-sorting processes during developectoderm crucial part in these cell-sorting processes during developMBoC6 m19.12/19.08 SORTING ment The appearance and disappearance of specific with another cadherin (cadherin 7) appears that helps SORTING hold the migrating cells cadherins correlateSORTING MBoC6and m19.12/19.08 OUT ce and disappearance of specific cadherins correlate with steps in embryonic development where cells regroup and change their contacts OUT together as loosely associated cell groups (Figure 19–8C) OUT Finally, when the cells development where cells regroup and change their contacts to create new tissue structures In the vertebrate embryo, for example, changes in aggregate to form a ganglion, they switch on expression of N-cadherin again If tube cell expressing structures the E-cadherin vertebrateneural embryo, for example, changes in cadherin expression are seen when the neural tube forms and pinches off from cellsIn expressing (A) N-cadherin inoverlying the emerging neural crest cells, theE-cadherin cells cells expressing cadherin 6BN-cadherin is artificially overexpressed the ectoderm: neural tube cells lose and acquire other cadare seencells when the neural tube forms and pinches off from cell expressing expressing N-cadherin failE-cadherin to escape from neural tube herins, (A) including N-cadherin, N-cadherin while the cells in the overlying cells expressing cadherin neural crest cadcell ectoderm expressingcontinue low rm: neural tube cells lose and the acquire other cell expressing cells to express E-cadherin (Figure 19–8A and B) Then, when the neural crest cells (C) level of E-cadherin Studies with cultured cells further support the idea that the homophilic bindhigh level of E-cadherin cadherin, while the cells in the overlying ectoderm continue migrate away from the neural tube, these cadherins become scarcely detectable, (B) ing Then, of cadherins controls these processes tissue segregation In a line of cultured expressing SORTING another cadherin (cadherin 7) appears that helps hold the migrating cells n (Figure 19–8A and B) when the neural crest cells andofcell 38 OUT high level of E-cadherin fibroblasts called L cells, for example, cadherins are not expressed and the cells he neural tube, these cadherins become scarcely detectable, together as loosely associated cell groups (Figure 19–8C) Finally, when the cells Figure 19–9 Cadherin-dependent cell aggregate formtransfected a ganglion, they expression of N-cadherin again If not adhere to one another When these cellstoare withswitch DNAonencod- Blisters are a painful reminder that it is not enough for epidermal cells to be firmly attached to one another: they must also be anchored to the underlying connective tissue As we noted earlier, the anchorage is mediated by integrins in the cells’ basal plasma membranes The extracellular Desmosome semidesmosome desmosome cadherin proteins cytoplasmic plaque made of intracellular linker proteins CYTOSOL ne CELL CELL • Sự xếp mang lại độ bền kéo dãn lớn cho biểu mơ, đặc tính biểu mơ bộc lộ, dai lớp biểu bì da CELL me • Một phức hợp phân tử cadherin khác kết nối với siêu sợi keratin (các sợi trung gian tìm thấy đặc hiệu tế bào biểu mô) CELL dle keratin filaments plaque of linker proteins mic eins ; r keratin filaments anchored to cytoplasmic plaque (A) 0.1 µm Desmosome (B) intercellular space basal plasma membrane of epithelial cell hemidesmosome CYTOSOL basal lamina interacting plasma membranes integrin proteins Semidesmosome 39 Liên kết dính desmosome 40 Liên kết dính desmosome 41 produces each heart beat Gap junctions in many tissues can be opened or closed in response to extracellular or intracellular signals The neurotransmitter dopamine, for Liên kết khe (Gap junction) gap junction interacting plasma membranes of cells and channel 1.5 nm in diameter CELL gap of 2–4 nm CELL (B) (A) 100 nm two connexons in register forming a cytosolic channel between adjacent cells connexon composed of six protein subunits different cell types at to the extracellular m Figure 20–28 Gap junct neighboring cells with a intercytosolic communic micrograph of a gap junc two cells in culture (B) A junction The drawing sho plasma membranes of tw The apposed membrane by protein assemblies ca (green), each of which is f identical protein subunits join across the intercellul aqueous channel connec of the two cells (A, from Communication [R.P Cox New York: Wiley, 1974 W from John Wiley & Sons, Các liên kết khe cho phép ion vô tế bào phân tử nhỏ từ tế bào sang tế bào khác Ví dụ: co đồng tế bào tim kích hoạt nhờ ghép nối điện thông qua liên kết khe 42 lium such as the lining of the small intestine of a vertebrate Here, a single layer of tall cells stands on a basal lamina, with the cells’ uppermost surface, or apex, m19.01/19.01 free and exposed to the extracellular medium.MBoC6 On their sides, or lateral surfaces, the cells make junctions with one another Two types of anchoring junctions link the cytoskeletons of adjacent cells: adherens junctions are anchorage sites for actin filaments; desmosomes are anchorage sites for intermediate filaments Two additional types of anchoring junctions link the cytoskeleton of the epithelial cells to the basal lamina: actin-linked cell–matrix junctions anchor actin filaments to the matrix, while hemidesmosomes anchor intermediate filaments to it to cell by adhesive junctions Cell–matrix attachments bond epithelial tissue to the connective tissue beneath it Tổng hợp APICAL tight junction seals gap between epithelial cells TIGHT JUNCTION junctional complex CELL–CELL ANCHORING JUNCTIONS adherens junction connects actin filament bundle in one cell with that in the next cell desmosome connects intermediate filaments in one cell to those in the next cell CHANNEL-FORMING JUNCTION gap junction allows the passage of small water-soluble molecules from cell to cell CELL–MATRIX ANCHORING JUNCTIONS BASAL actin-linked cell–matrix junction anchors actin filaments in cell to extracellular matrix hemidesmosome anchors intermediate filaments in a cell to extracellular matrix 43 Cancer metastasis 44 45 Tham khảo • Lodish, H F (2016) Molecular cell biology (Eight edition) W.H Freeman-Macmillan Learning • Alberts, B (2018) Essential cell biology (Fifth edition) Garland Science, Taylor and Francis Group • Alberts, B (2015) Molecular biology of the cell (Sixth edition) Garland Science, Taylor and Francis Group 46 ... (TISSUE) Chất ngoại bào Liên kết tế bào (Cells – Cell junctions) (Extracellular matrix) Mô liên kết (Connective tissue) Mô thần kinh Biểu mô Mô (nervous tissue) (Epithelial tissue) (Muscle tissue) ... CHAPTER 20 Cell Communities: Tissues, Stem Cells, and Cancer Các liên kết chặt (tigh junctions) 704 CHAPTER 20 LUMEN interacting plasma membranes Cell Communities: Tissues, Stem Cells, and Cancer... membranes LUMEN CELL CELL tracer tight molecule junction CELL tight junction intercellular space tight junction intercellular tight sealing CELL space junction strands of occludin and claudin (A)