RT Journal Article
SR Electronic
T1 Multiparameter stimulation mapping of signaling states in single pediatric immune cells reveals heightened tonic activation during puberty
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.14.516371
DO 10.1101/2022.11.14.516371
A1 Farmer, Rohit
A1 Apps, Richard
A1 Quiel, Juan
A1 Sellers, Brian A.
A1 Cheung, Foo
A1 Chen, Jinguo
A1 Mukherjee, Amrita
A1 McGuire, Peter J.
A1 Tsang, John S.
YR 2022
UL http://biorxiv.org/content/early/2022/11/16/2022.11.14.516371.abstract
AB Cellular stimulation via factors such as cytokines followed by multiparameter single-cell measurements is a powerful approach to interrogate cellular functions. However, transforming such high-dimensional data into biological insights presents unique challenges, particularly given the extensive response heterogeneity among single cells, such as the presence of bimodal responding versus non-responding subpopulations upon stimulation. Here we present an unsupervised high-dimensional approach for analyzing stimulation responses at the single cell level (HDStIM) and apply it to evaluate how pediatric development may shape peripheral immune cell signaling states and responsiveness to stimulations in 42 subjects (age: 2 - 16). We show that in comparison to the conventional approach of assessing one marker at a time by averaging across single cells, HDStIM can effectively learn, in an unsupervised fashion, the multi-parameter signature of responding versus non-responding cells to accurately quantify responses within cell populations. HDStIM reveals that the extent of pre-stimulation/baseline activation of interferon-related and TCR signaling molecules in myeloid and T cells, respectively, increases during puberty. This suggests that puberty is marked by a heightened “tonic” activation state in these cells, perhaps to strengthen defense against pathogens during this period of human development.Competing Interest StatementThe authors have declared no competing interest.