Dataset Information

Social Network Architecture of Human Immune Cells Unveiled by Quantitative Proteomics

ABSTRACT: The immune system is unique in its dynamic interplay between numerous cell types. However, a system-wide view of how immune cells communicate to protect against disease has not been established. Here, we applied high-resolution mass spectrometry-based proteomics to generate a publicly accessible protein atlas of 28 primary human immune cell populations in steady and activated states at a depth of > 10,000 proteins. Cell-type-specific protein copy numbers reveal that immune cells are most specialized at the level of ligands and receptors, thereby connecting distinct functions of the immune system. By integrating total and secreted proteomes, we deduce paracrine immune dynamics upon microbial encounter and discover fundamental intercellular communication structures as well as novel connections between cellular senders and receivers of biological information. Our comprehensive cell-type-resolved proteomic resource of human immune cells provides a framework for the orchestration of cellular interplay and a reference for altered communication associated with pathology.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood

SUBMITTER: Mario Oroshi

LAB HEAD: Matthias Mann

PROVIDER: PXD004352 | Pride | 2017-03-15

REPOSITORIES: Pride

ACCESS DATA

Publications

Social network architecture of human immune cells unveiled by quantitative proteomics.

Rieckmann Jan C JC Geiger Roger R Hornburg Daniel D Wolf Tobias T Kveler Ksenya K Jarrossay David D Sallusto Federica F Shen-Orr Shai S SS Lanzavecchia Antonio A Mann Matthias M Meissner Felix F

Nature immunology 20170306 5

The immune system is unique in its dynamic interplay between numerous cell types. However, a system-wide view of how immune cells communicate to protect against disease has not yet been established. We applied high-resolution mass-spectrometry-based proteomics to characterize 28 primary human hematopoietic cell populations in steady and activated states at a depth of >10,000 proteins in total. Protein copy numbers revealed a specialization of immune cells for ligand and receptor expression, ther ...[more]

PMID: 28263321

Similar Datasets

Project description:The proper balance of excitatory and inhibitory neurons is crucial to normal processing of somatosensory information in the dorsal spinal cord. Two neural basic helix-loop-helix transcription factors, Ascl1 and Ptf1a, are essential for generating the correct number and sub-type of neurons in multiple regions of the nervous system. M-BM- In the dorsal spinal cord, Ascl1 and Ptf1a have contrasting functions in specifying inhibitory versus excitatory neurons. To understand how Ascl1 and Ptf1a function in these processes, we identified their direct transcriptional targets genome-wide in the embryonic mouse neural tube using ChIP-Seq and RNA-Seq. We show that Ascl1 and Ptf1a regulate the specification of excitatory and inhibitory neurons in the dorsal spinal cord through direct regulation of distinct homeodomain transcription factors known for their function in neuronal sub-type specification. Besides their roles in regulating these homeodomain factors, Ascl1 and Ptf1a each function differently during neuronal development with Ascl1 directly regulating genes with roles in several steps of the neurogenic program including, Notch signaling, neuronal differentiation, axon guidance, and synapse formation. In contrast, Ptf1a directly regulates genes encoding components of the neurotransmitter machinery in inhibitory neurons, and other later aspects of neural development distinct from those regulated by Ascl1. Moreover, Ptf1a represses the excitatory neuronal fate by directly repressing several targets of Ascl1. Examination of the Ascl1 and Ptf1a bound sequences shows they are enriched for a common E-Box with a GC core and with additional motifs used by Sox, Rfx, Pou, and Homeodomain factors. Ptf1a bound sequences are uniquely enriched in an E-Box with a GA/TC core and in the binding motif for its co-factor Rbpj, providing two keys to specificity of Ptf1a binding. The direct transcriptional targets identified for Ascl1 and Ptf1a provide a molecular understanding for how they function in neuronal development, particularly as key regulators of homeodomain transcription factors required for neuronal sub-type specification. Examination of Ascl1 and Ptf1a genome-wide binding in developing neural tube.

Dataset Information

Social Network Architecture of Human Immune Cells Unveiled by Quantitative Proteomics

Publications

Social network architecture of human immune cells unveiled by quantitative proteomics.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure