Revealing the spatio-phenotypic patterning of cells in healthy and tumor tissues with mLSR-3D and STAPL-3D.

Autor: van Ineveld RL; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Cancer Genomics Netherlands, Oncode Institute, Utrecht, the Netherlands., Kleinnijenhuis M; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Cancer Genomics Netherlands, Oncode Institute, Utrecht, the Netherlands., Alieva M; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Cancer Genomics Netherlands, Oncode Institute, Utrecht, the Netherlands., de Blank S; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Cancer Genomics Netherlands, Oncode Institute, Utrecht, the Netherlands., Barrera Roman M; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Cancer Genomics Netherlands, Oncode Institute, Utrecht, the Netherlands., van Vliet EJ; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Cancer Genomics Netherlands, Oncode Institute, Utrecht, the Netherlands., Martínez Mir C; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Cancer Genomics Netherlands, Oncode Institute, Utrecht, the Netherlands., Johnson HR; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Cancer Genomics Netherlands, Oncode Institute, Utrecht, the Netherlands., Bos FL; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Cancer Genomics Netherlands, Oncode Institute, Utrecht, the Netherlands., Heukers R; QVQ Holding BV, Utrecht, the Netherlands., Chuva de Sousa Lopes SM; Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, the Netherlands., Drost J; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Cancer Genomics Netherlands, Oncode Institute, Utrecht, the Netherlands., Dekkers JF; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Cancer Genomics Netherlands, Oncode Institute, Utrecht, the Netherlands., Wehrens EJ; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Cancer Genomics Netherlands, Oncode Institute, Utrecht, the Netherlands., Rios AC; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. a.c.rios@prinsesmaximacentrum.nl.; Cancer Genomics Netherlands, Oncode Institute, Utrecht, the Netherlands. a.c.rios@prinsesmaximacentrum.nl.
Jazyk: angličtina
Zdroj: Nature biotechnology [Nat Biotechnol] 2021 Oct; Vol. 39 (10), pp. 1239-1245. Date of Electronic Publication: 2021 Jun 03.
DOI: 10.1038/s41587-021-00926-3
Abstrakt: Despite advances in three-dimensional (3D) imaging, it remains challenging to profile all the cells within a large 3D tissue, including the morphology and organization of the many cell types present. Here, we introduce eight-color, multispectral, large-scale single-cell resolution 3D (mLSR-3D) imaging and image analysis software for the parallelized, deep learning-based segmentation of large numbers of single cells in tissues, called segmentation analysis by parallelization of 3D datasets (STAPL-3D). Applying the method to pediatric Wilms tumor, we extract molecular, spatial and morphological features of millions of cells and reconstruct the tumor's spatio-phenotypic patterning. In situ population profiling and pseudotime ordering reveals a highly disorganized spatial pattern in Wilms tumor compared to healthy fetal kidney, yet cellular profiles closely resembling human fetal kidney cells could be observed. In addition, we identify previously unreported tumor-specific populations, uniquely characterized by their spatial embedding or morphological attributes. Our results demonstrate the use of combining mLSR-3D and STAPL-3D to generate a comprehensive cellular map of human tumors.
(© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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