first molecular characterization of b. glabrata hemocyte...

1
Innate immune memory process in Biomphalaria glabrata snails: a comparative multi-omic approach to decipher the function and role-played by the hemocyte immune cells Rémi Pichon 1 , Silvain Pinaud 1 , Maud Laffitte 1 , Cristian Chaparro 1 , Emmanuel Vignal 1 , Guillaume Charrière 1 , David Duval 1 , Richard Galinier 1 , Benjamin Gourbal 1 . 1 Hosts Pathogens Environments Interactions, UMR 5244, CNRS, IFREMER, UM, University of Perpignan Via Domitia F- 66860 Perpignan, France. Acknowledgements: this work is supported by « BQR » grant of the University of Perpignan Via Domitia First molecular characterization of B. glabrata hemocyte populations at a single cell level Objectives : Identify hemocyte sub-populations of B. glabrata involved in IIM response towards S. mansoni parasite based on different transcriptomic profiles using Single-Cell RNA sequencing technology Contacts: [email protected] One world – One health – One ocean RNA sequencing using Novaseq technology from the MGX platform Cell sorting with 10x chromium system Hemocyte samples recovery for naives, primo infested and challenged snails. scRNA seq protocole In silico analysis using Cell ranger and Seurat Sample data integration and in vivo validation Hemolymph collection Hemocytes Hemocytes stained with MCDh Integration of all data may allow us to identify the transcriptomic populations able to respond to the infection and thus support IIM. Two technics will be used to make the link between hemocyte transcriptional and morphological populations : - Flow cytometry technique : sorting hemocytes based on morphological characteristics and test each population using qPCR for expression of gene markers previously identified by scRNA. - In Situ Hybridization (ISH) targeting scRNA gene markers on hemocytes. Cells and enzyme Oil Gel bead 2 1 0 -1 -2 Expression - Oxydative phosphorylation - Regulation of cellular protein metabolic process - Regulation of lymphocyte migration - Regulation of neutrophil chemotaxis - Regulation of catalytic activity - Regulation of necrotic cell death - DNA replication - Regulation of catalytic activity - Oligosaccharide metabolic process - rRNA metabolism 0 (n = 668) 1 (n = 435) 2 (n = 275) 3 (n = 214) 4 (n = 139) 5 (n = 109) 6 (n = 82) 7 (n = 66) 8 (n = 46) 9 (n = 39) Granulocytes Hyalinocytes Blast like cells Light microscopy imaging of the three hemocyte populations from B. glabrata stained with MCDh Hemocyte transcriptomic populations Hemocyte morphological populations T-disctributed stochastic neighbor embedding (tSNE) projection of 10 naive hemocyte clusters Heatmap of the top 25 marker genes by transcriptomic cluster and gene ontology enrichment Uniform Manifold Approximation and Projection (uMAP) projection of the entire kinetic of infestation en re infestation Bg BRE Sm BRE Naive P1D Primo infestation Bg BRE P15D C1D Challenge Transcriptomic populations and gene markers Use of scRNA seq allows us to demonstrate a greater hemocyte population diversity. 10 Transcriptomic populations are defined among the 3 hemocyte morphological populations In the early 2000’s, several studies have highlighted the ability of invertebrates immune system to be primed, protecting the individual when meets the same pathogen twice during its life span, this process is called « innate immune memory » (IIM). This IIM has recently been demonstrated for B. glabrata snails against S. mansoni infestation and it is characterized by a shift from a cellular response to a humoral response, certainly carried by the snail innate immune cells, the hemocytes. Enrichment analysis using Gene Ontology annotation allowed us to determine the functions associated with each transcriptomic population, based on gene markers. Results in number : Genome mapping rate : 90,1% Recovered cells : 2 073 Unique genes detected : 16 926 Median genes per cell : 1 885 Number of reads : 185 257 268

Upload: others

Post on 08-Sep-2021

1 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: First molecular characterization of B. glabrata hemocyte ...ihpe.univ-perp.fr/.../2021/06/EEID-pst_PICHON_Remi.pdf · Sample data integration and in vivo validation Hemolymph collection

Innate immune memory process in Biomphalaria glabrata snails: acomparative multi-omic approach to decipher the function and role-playedby the hemocyte immune cells

Rémi Pichon1, Silvain Pinaud1, Maud Laffitte1, Cristian Chaparro1, Emmanuel Vignal1, Guillaume Charrière1,David Duval1, Richard Galinier1, Benjamin Gourbal1.

1Hosts Pathogens Environments Interactions, UMR 5244, CNRS, IFREMER, UM, University of Perpignan Via Domitia F-66860 Perpignan, France.

Acknowledgements: this work is supported by « BQR » grant of the University of Perpignan Via Domitia

First molecular characterization of B. glabrata hemocyte populations at a single cell level

Objectives : Identify hemocyte sub-populations of B. glabrata involved in IIM response towards S. mansoni parasite based ondifferent transcriptomic profiles using Single-Cell RNA sequencing technology

Contacts: [email protected]

One world – One health – One ocean

RNA sequencing using Novaseqtechnology from the MGX platform

Cell sorting with 10x chromium system

Hemocyte samples recovery for naives, primo infested and challenged snails.

scRNA seq protocole

In silico analysis using Cell ranger and Seurat

Sample data integration and in vivo validation

Hemolymph collection

Hemocytes

Hemocytes stained with MCDh

Integration of all data may allow us to identify the

transcriptomic populations able to respond to the

infection and thus support IIM.

Two technics will be used to make the link between hemocytetranscriptional and morphological populations :

- Flow cytometry technique : sorting hemocytes based onmorphological characteristics and test each populationusing qPCR for expression of gene markers previouslyidentified by scRNA.

- In Situ Hybridization (ISH) targeting scRNA gene markers onhemocytes.

Cells and

enzyme

Oil

Gel bead

2 1 0 -1 -2

Expression

- Oxydative phosphorylation

- Regulation of cellular protein metabolic process

- Regulation of lymphocyte migration

- Regulation of neutrophil chemotaxis

- Regulation of catalytic activity

- Regulation of necrotic cell death

- DNA replication

- Regulation of catalytic activity

- Oligosaccharide metabolic process

- rRNA metabolism

0 (n = 668)

1 (n = 435)

2 (n = 275)

3 (n = 214)

4 (n = 139)

5 (n = 109)

6 (n = 82)

7 (n = 66)

8 (n = 46)

9 (n = 39)

Granulocytes Hyalinocytes Blast like cellsLight microscopy imaging of the three hemocyte populations from B. glabrata stained with MCDh

Hemocyte transcriptomic populations

Hemocyte morphological populations

T-disctributed stochastic neighbor embedding (tSNE) projection of 10 naive hemocyte clusters

Heatmap of the top 25 marker genes by transcriptomic cluster and gene ontology enrichment

Uniform Manifold Approximation and Projection (uMAP) projection of the entire kinetic of infestation en re infestation

Bg BRE

Sm BRE

Naive

P1DPrimo infestation

Bg BRE

P15D

C1DChallenge

Transcriptomic populations and gene markersUse of scRNA seq allows us to demonstrate a greater

hemocyte population diversity.

10 Transcriptomic populations are defined

among the 3 hemocytemorphological populations

In the early 2000’s, several studies have highlighted the ability of invertebrates immune system to be primed, protecting the individual when meets the samepathogen twice during its life span, this process is called « innate immune memory » (IIM). This IIM has recently been demonstrated for B. glabrata snailsagainst S. mansoni infestation and it is characterized by a shift from a cellular response to a humoral response, certainly carried by the snail innate immunecells, the hemocytes.

Enrichment analysis using Gene Ontology

annotation allowed us to determine the

functions associated with each

transcriptomic population, based on

gene markers.

Results in number :

Genome mapping rate : 90,1%

Recovered cells : 2 073

Unique genes detected : 16 926

Median genes per cell : 1 885

Number of reads : 185 257 268