TY - JOUR
T1 - Anaplastic transformation in thyroid cancer revealed by single-cell transcriptomics
AU - Lu, Lina
AU - Wang, Jennifer Rui
AU - Henderson, Ying C.
AU - Bai, Shanshan
AU - Yang, Jie
AU - Hu, Min
AU - Shiau, Cheng Kai
AU - Pan, Timothy
AU - Yan, Yuanqing
AU - Tran, Tuan M.
AU - Li, Jianzhuo
AU - Kieser, Rachel
AU - Zhao, Xiao
AU - Wang, Jiping
AU - Nurieva, Roza
AU - Williams, Michelle D.
AU - Cabanillas, Maria E.
AU - Dadu, Ramona
AU - Busaidy, Naifa Lamki
AU - Zafereo, Mark
AU - Navin, Nicholas
AU - Lai, Stephen Y.
AU - Gao, Ruli
N1 - Publisher Copyright:
Copyright: © 2023, Lu et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - The deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated thyroid cancer (DTC); however, the complex intratumor transformation process is poorly understood. We investigated an anaplastic transformation model by dissecting both cell lineage and cell fate transitions using single-cell transcriptomic and genetic alteration data from patients with different subtypes of thyroid cancer. The resulting spectrum of ATC transformation included stress-responsive DTC cells, inflammatory ATC cells (iATCs), and mitotic-defective ATC cells and extended all the way to mesenchymal ATC cells (mATCs). Furthermore, our analysis identified 2 important milestones: (a) a diploid stage, in which iATC cells were diploids with inflammatory phenotypes and (b) an aneuploid stage, in which mATCs gained aneuploid genomes and mesenchymal phenotypes, producing excessive amounts of collagen and collagen-interacting receptors. In parallel, cancer-associated fibroblasts showed strong interactions among mesenchymal cell types, macrophages shifted from M1 to M2 states, and T cells reprogrammed from cytotoxic to exhausted states, highlighting new therapeutic opportunities for the treatment of ATC.
AB - The deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated thyroid cancer (DTC); however, the complex intratumor transformation process is poorly understood. We investigated an anaplastic transformation model by dissecting both cell lineage and cell fate transitions using single-cell transcriptomic and genetic alteration data from patients with different subtypes of thyroid cancer. The resulting spectrum of ATC transformation included stress-responsive DTC cells, inflammatory ATC cells (iATCs), and mitotic-defective ATC cells and extended all the way to mesenchymal ATC cells (mATCs). Furthermore, our analysis identified 2 important milestones: (a) a diploid stage, in which iATC cells were diploids with inflammatory phenotypes and (b) an aneuploid stage, in which mATCs gained aneuploid genomes and mesenchymal phenotypes, producing excessive amounts of collagen and collagen-interacting receptors. In parallel, cancer-associated fibroblasts showed strong interactions among mesenchymal cell types, macrophages shifted from M1 to M2 states, and T cells reprogrammed from cytotoxic to exhausted states, highlighting new therapeutic opportunities for the treatment of ATC.
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U2 - 10.1172/JCI169653
DO - 10.1172/JCI169653
M3 - Article
C2 - 37053016
AN - SCOPUS:85160966247
SN - 0021-9738
VL - 133
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 11
M1 - e169653
ER -