Nghiên cứu siêu cấu trúc và động học của bào quan nội bào trong hội chứng Down
Tóm tắt
Các bào quan nội bào sớm đã được quan sát thấy mở rộng trong bệnh Alzheimer (AD) và hội chứng Down (DS) bằng kính hiển vi huỳnh quang thông thường với độ phân giải tương ứng với kích thước bào quan nội bào (hàng trăm nm). Để vượt qua giới hạn nhiễu xạ, chúng tôi đã sử dụng kính hiển vi cấu trúc ánh sáng siêu phân giải (SR-SIM) và kính hiển vi điện tử truyền qua (TEM) để phân tích bào quan nội bào sớm trong hội chứng DS.
Bằng phương pháp miễn dịch huỳnh quang và kính hiển vi huỳnh quang, chúng tôi xác nhận rằng thể tích của các điểm dương tính với kháng nguyên bào quan nội bào sớm 1 (EEA1) lớn hơn 13–19% trong các tế bào nguyên bào sợi và nơ-ron lấy từ tế bào gốc phôi (iPSC) của các cá nhân bị hội chứng DS, cũng như ở các nơ-ron cholinergic của vùng vỏ não nền (BFCN) của chuột Ts65Dn mô phỏng hội chứng DS. Tuy nhiên, các cấu trúc dương tính với EEA1 được hình ảnh hóa bằng TEM hoặc SR-SIM sau khi cố định hóa học có kích thước bình thường nhưng có sự tập hợp lại với nhau. Để giải quyết những mâu thuẫn này, chúng tôi đã hình ảnh hóa các tế bào nguyên bào sợi của DS đã được bảo tồn tối ưu bằng cách đông lạnh áp suất cao (HPF) bằng TEM và phát hiện rằng các bào quan nội bào sớm dày đặc hơn 75% nhưng vẫn giữ kích thước bình thường.
Giải trình tự RNA của các tế bào nguyên bào sợi DS và euploid đã tiết lộ một phân nhóm các gen biểu hiện khác biệt liên quan đến phân loại hàng hóa tại các cơ thể đa bào (MVBs). Do đó, chúng tôi đã nghiên cứu động lực của quá trình nội thực bào, tái chế và phân hủy phụ thuộc vào MVB trong các tế bào nguyên bào sợi DS. Chúng tôi không thấy sự thay đổi trong nội thực bào, tăng cường tái chế và phân hủy bị trì hoãn, cho thấy có một "tắc nghẽn giao thông" trong bào quan nội bào.
Từ khóa
#hội chứng Down #bào quan nội bào #kính hiển vi điện tử #siêu phân giải #nội thực bàoTài liệu tham khảo
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