Cảnh quan biểu hiện và sự đồng điều chỉnh của các gen lão hóa đặc hiệu theo mô và loại tế bào ở người

Springer Science and Business Media LLC - 2022
Peng Xu1,2,3, Minghui Wang3,1,2, Won-min Song3,1,2, Qian Wang3,1,2, Guo-Cheng Yuan2,4, Peter H. Sudmant5,6, Habil Zare7,8, Zhidong Tu3,1,2, Miranda E. Orr9,10,11, Bin Zhang3,1,2,12
1Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, USA
2Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA
3Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, USA
4Institute for Precision Medicine, Icahn School of Medicine at Mount Sinai, New York, USA
5Department of Integrative Biology, University of California, Berkeley, Berkeley, USA
6Center for Computational Biology, University of California, Berkeley, Berkeley, USA
7Department of Cell Systems & Anatomy, The University of Texas Health Science Center, San Antonio, USA
8Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, USA
9Section of Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, USA
10Salisbury VA Medical Center, Salisbury, USA
11Sticht Center for Healthy Aging and Alzheimer’s Prevention, Wake Forest School of Medicine, Winston-Salem, USA
12Department of Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, USA

Tóm tắt

Lão hóa tế bào là một phản ứng căng thẳng phức tạp ảnh hưởng đến chức năng tế bào và sức khỏe của cơ thể. Nhiều yếu tố phát triển và môi trường, chẳng hạn như tín hiệu nội tại của tế bào, bức xạ, căng thẳng oxy hóa, gen ung thư và sự tích tụ protein, kích hoạt các gen và con đường có thể dẫn đến lão hóa. Đã có những nỗ lực to lớn để xác định và đặc trưng hóa các gen lão hóa (SnGs) trong các hệ thống căng thẳng và bệnh tật. Tuy nhiên, sự phổ biến của các tế bào lão hóa trong các mô khỏe mạnh của con người và chữ ký biểu hiện SnG toàn cầu ở các loại tế bào khác nhau chưa được hiểu rõ. Nghiên cứu này đã thực hiện một phân tích mạng lưới gen tích hợp dữ liệu RNA-seq của tế bào đơn và môi trường tổng thể trong các mô người không bị bệnh để điều tra chữ ký đồng biểu hiện SnG và tính đặc hiệu của chúng theo loại tế bào. Thông qua phân tích mạng lưới phiên mã toàn diện của 50 mô người trong dự án Biểu hiện Genotype-Tissue Expression (GTEx), chúng tôi đã xác định các mô đun gen giàu SnG, đặc trưng hóa các mẫu đồng biểu hiện SnG và xây dựng các mạng lưới SnG tổng hợp trên các mô chính của cơ thể người. Các phương pháp mạng lưới của chúng tôi đã xác định 51 SnG được bảo tồn cao ở tất cả các mô người, bao gồm cả các điều hòa viên tập trung vào CDKN1A (p21) điều khiển tiến trình chu kỳ tế bào và kiểu hình tiết liên quan đến lão hóa (SASP). Các mô đun giàu SnG cho thấy tính đặc hiệu theo loại tế bào đáng kể, đặc biệt là ở sợi bào, tế bào nội mô và tế bào miễn dịch. Các phân tích thêm về dữ liệu RNA-seq của tế bào đơn và dữ liệu phiên mã không gian đã xác thực độc lập những chữ ký SnG đặc hiệu theo loại tế bào được dự đoán bởi phân tích mạng. Nghiên cứu này đã tiết lộ có hệ thống các tổ chức đồng điều chỉnh và tính đặc hiệu theo loại tế bào của SnGs trong các mô chính của con người, điều này có thể phục vụ như một bản thiết kế cho các nghiên cứu trong tương lai để lập bản đồ các tế bào lão hóa và các tương tác tế bào của chúng trong các mô người.

Từ khóa

#lão hóa tế bào #gen lão hóa #phân tích mạng lưới gen #RNA-seq #mô người #tính đặc hiệu theo loại tế bào

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