CellRank for directed single-cell fate mapping
Pingmin Wei,Yangyang Li +1 more
TLDR
In this article , a trajectory inference approach for single-cell fate mapping in diverse scenarios, including regeneration, reprogramming and disease, for which direction is unknown, is presented, which combines the robustness of trajectory inference with directional information from RNA velocity, taking into account the gradual and stochastic nature of cellular fate decisions.Abstract:
Computational trajectory inference enables the reconstruction of cell state dynamics from single-cell RNA sequencing experiments. However, trajectory inference requires that the direction of a biological process is known, largely limiting its application to differentiating systems in normal development. Here, we present CellRank ( https://cellrank.org ) for single-cell fate mapping in diverse scenarios, including regeneration, reprogramming and disease, for which direction is unknown. Our approach combines the robustness of trajectory inference with directional information from RNA velocity, taking into account the gradual and stochastic nature of cellular fate decisions, as well as uncertainty in velocity vectors. On pancreas development data, CellRank automatically detects initial, intermediate and terminal populations, predicts fate potentials and visualizes continuous gene expression trends along individual lineages. Applied to lineage-traced cellular reprogramming data, predicted fate probabilities correctly recover reprogramming outcomes. CellRank also predicts a new dedifferentiation trajectory during postinjury lung regeneration, including previously unknown intermediate cell states, which we confirm experimentally. read more
Citations
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Mapping the developing human immune system across organs
Chenqu Suo,Emma Dann,Issac Goh,Laura Jardine,Vitalii Kleshchevnikov,Jong-Eun Park,Rachel A. Botting,Emily Stephenson,Justin Engelbert,Zewen K. Tuong,Krzysztof Polanski,Nadav Yayon,Chuan Xu,Ondrej Suchanek,Rasa Elmentaite,Cecilia Conde,Peng He,Sophie Pritchard,Mohiuddin Miah,Corina Moldovan,Alexander S. Steemers,M. Julieta Del Prete,John C. Marioni,Menna R. Clatworthy,Muzlifah Haniffa,Sarah A. Teichmann +25 more
TL;DR: A comprehensive single-cell RNA sequencing atlas of human developing immune system is performed together with antigen-receptor sequencing and spatial transcriptomics to reconstruct the developing human immune system and identifies, characterised and functionally validated the properties of human prenatal B1 cells and the origin of unconventional T cells.
Journal ArticleDOI
T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10
Vidhya M Ravi,Nicolas Neidert,Paulina Will,Kevin Joseph,Julian P Maier,Jan Kückelhaus,Lea Vollmer,Jonathan M Goeldner,Simon P Behringer,Florian Scherer,Melanie Boerries,Marie Follo,Tobias Weiss,Daniel Delev,Julius M Kernbach,Pamela Franco,Nils Schallner,Christine Dierks,Maria Stella Carro,Ulrich G. Hofmann,Christian Fung,Roman Sankowski,Marco Prinz,Jürgen Beck,Henrike Salié,Bertram Bengsch,Oliver Schnell,Dieter Henrik Heiland +27 more
TL;DR: In this article , a subset of Interleukin-10-releasing HMOX1+ myeloid cells, spatially localizing to mesenchymal-like tumor regions, drive T-cell exhaustion and thus contribute to the immunosuppressive tumor microenvironment.
Journal ArticleDOI
T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10
Vidhya M Ravi,Nicolas Neidert,Paulina Will,Kevin Joseph,Julian P Maier,Jan Kückelhaus,Lea Vollmer,Jonathan M Goeldner,Simon P Behringer,Florian Scherer,Melanie Boerries,Marie Follo,Tobias Weiss,Daniel Delev,Julius M Kernbach,Pamela Franco,Nils Schallner,Christine Dierks,Maria Stella Carro,Ulrich G. Hofmann,Christian Fung,Roman Sankowski,Marco Prinz,Jürgen Beck,Henrike Salié,Bertram Bengsch,Oliver Schnell,Dieter Henrik Heiland +27 more
TL;DR: In this paper , a subset of Interleukin-10-releasing HMOX1+ myeloid cells, spatially localizing to mesenchymal-like tumor regions, drive T-cell exhaustion and thus contribute to the immunosuppressive tumor microenvironment.
Journal ArticleDOI
Liver tumour immune microenvironment subtypes and neutrophil heterogeneity
Ruidong Xue,Qiming Zhang,Qi-Hua Cao,Ruirui Kong,Xiao Xiang,Hengkang Liu,Mei Feng,Fangyanni Wang,Jinghui Cheng,Zhao Li,Qimin Zhan,Mi Deng,Jiye Zhu,Zemin Zhang,Ning Zhang +14 more
Journal ArticleDOI
RNA velocity unraveled
TL;DR: It is argued for a more rigorous approach to RNA velocity, and a framework for Markovian analysis that points to directions for improvement and mitigation of current problems is presented.
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