Clonal multi-omics reveals Bcor as a negative regulator of emergency dendritic cell development

Luyi Tian; Sara Tomei; Jaring Schreuder; Tom S. Weber; Daniela Amann-Zalcenstein; Dawn S. Lin; Jessica Tran; Cindy Audiger; Mathew Chu; Andrew Jarratt; Tracy Willson; Adrienne Hilton; Ee Shan Pang; Timothy Patton; Madison Kelly; Shian Su; Quentin Gouil; Peter Diakumis; Melanie Bahlo; Toby Sargeant; Lev M. Kats; Philip D. Hodgkin; Meredith O'Keeffe; Ashley P. Ng; Matthew E. Ritchie; Shalin H. Naik

doi:10.1016/j.immuni.2021.03.012

Clonal multi-omics reveals Bcor as a negative regulator of emergency dendritic cell development

Luyi Tian, Sara Tomei, Jaring Schreuder, Tom S. Weber, Daniela Amann-Zalcenstein, Dawn S. Lin, Jessica Tran, Cindy Audiger, Mathew Chu, Andrew Jarratt, Tracy Willson, Adrienne Hilton, Ee Shan Pang, Timothy Patton, Madison Kelly, Shian Su, Quentin Gouil, Peter Diakumis, Melanie Bahlo, Toby SargeantLev M. Kats, Philip D. Hodgkin, Meredith O'Keeffe, Ashley P. Ng, Matthew E. Ritchie, Shalin H. Naik

Research output: Contribution to journal › Article › Research › peer-review

15 Citations (Scopus)

Abstract

Despite advances in single-cell multi-omics, a single stem or progenitor cell can only be tested once. We developed clonal multi-omics, in which daughters of a clone act as surrogates of the founder, thereby allowing multiple independent assays per clone. With SIS-seq, clonal siblings in parallel “sister” assays are examined either for gene expression by RNA sequencing (RNA-seq) or for fate in culture. We identified, and then validated using CRISPR, genes that controlled fate bias for different dendritic cell (DC) subtypes. This included Bcor as a suppressor of plasmacytoid DC (pDC) and conventional DC type 2 (cDC2) numbers during Flt3 ligand-mediated emergency DC development. We then developed SIS-skew to examine development of wild-type and Bcor-deficient siblings of the same clone in parallel. We found Bcor restricted clonal expansion, especially for cDC2s, and suppressed clonal fate potential, especially for pDCs. Therefore, SIS-seq and SIS-skew can reveal the molecular and cellular mechanisms governing clonal fate.

Original language	English
Pages (from-to)	1338-1351.e9
Number of pages	24
Journal	Immunity
Volume	54
Issue number	6
DOIs	https://doi.org/10.1016/j.immuni.2021.03.012
Publication status	Published - 8 Jun 2021

Keywords

cellular barcoding
clonal lineage tracing
CRISPR minipool
dendritic cell
Flt3 ligand
immunotherapy
single-cell fate
single-cell RNA-seq
state-fate

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.immuni.2021.03.012

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Tian, L., Tomei, S., Schreuder, J., Weber, T. S., Amann-Zalcenstein, D., Lin, D. S., Tran, J., Audiger, C., Chu, M., Jarratt, A., Willson, T., Hilton, A., Pang, E. S., Patton, T., Kelly, M., Su, S., Gouil, Q., Diakumis, P., Bahlo, M., ... Naik, S. H. (2021). Clonal multi-omics reveals Bcor as a negative regulator of emergency dendritic cell development. Immunity, 54(6), 1338-1351.e9. https://doi.org/10.1016/j.immuni.2021.03.012

@article{13c01e11816645e6ad71a8d6dd74a632,

title = "Clonal multi-omics reveals Bcor as a negative regulator of emergency dendritic cell development",

abstract = "Despite advances in single-cell multi-omics, a single stem or progenitor cell can only be tested once. We developed clonal multi-omics, in which daughters of a clone act as surrogates of the founder, thereby allowing multiple independent assays per clone. With SIS-seq, clonal siblings in parallel “sister” assays are examined either for gene expression by RNA sequencing (RNA-seq) or for fate in culture. We identified, and then validated using CRISPR, genes that controlled fate bias for different dendritic cell (DC) subtypes. This included Bcor as a suppressor of plasmacytoid DC (pDC) and conventional DC type 2 (cDC2) numbers during Flt3 ligand-mediated emergency DC development. We then developed SIS-skew to examine development of wild-type and Bcor-deficient siblings of the same clone in parallel. We found Bcor restricted clonal expansion, especially for cDC2s, and suppressed clonal fate potential, especially for pDCs. Therefore, SIS-seq and SIS-skew can reveal the molecular and cellular mechanisms governing clonal fate.",

keywords = "cellular barcoding, clonal lineage tracing, CRISPR minipool, dendritic cell, Flt3 ligand, immunotherapy, single-cell fate, single-cell RNA-seq, state-fate",

author = "Luyi Tian and Sara Tomei and Jaring Schreuder and Weber, {Tom S.} and Daniela Amann-Zalcenstein and Lin, {Dawn S.} and Jessica Tran and Cindy Audiger and Mathew Chu and Andrew Jarratt and Tracy Willson and Adrienne Hilton and Pang, {Ee Shan} and Timothy Patton and Madison Kelly and Shian Su and Quentin Gouil and Peter Diakumis and Melanie Bahlo and Toby Sargeant and Kats, {Lev M.} and Hodgkin, {Philip D.} and Meredith O'Keeffe and Ng, {Ashley P.} and Ritchie, {Matthew E.} and Naik, {Shalin H.}",

note = "Funding Information: We thank WEHI core facilities, including Bioservices, Centre for Dynamic Imaging, Flow cytometry, and Genomics; D. Hilton, M. Blewitt, S. Nutt, S. Taoudi, and J. Powell for critical reading of the manuscript; and J.-G. Zhang for Flt3L. This work was supported by grants from the National Health and Medical Research Council , Australia ( GNT1062820 , GNT1100033 , GNT1101378 , GNT1124812 , and GNT1145184 ), and the Australia Research Council {\textquoteright}s special initiative Stem Cells Australia. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = jun,

day = "8",

doi = "10.1016/j.immuni.2021.03.012",

language = "English",

volume = "54",

pages = "1338--1351.e9",

journal = "Immunity",

issn = "1074-7613",

publisher = "Elsevier",

number = "6",

}

Tian, L, Tomei, S, Schreuder, J, Weber, TS, Amann-Zalcenstein, D, Lin, DS, Tran, J, Audiger, C, Chu, M, Jarratt, A, Willson, T, Hilton, A, Pang, ES, Patton, T, Kelly, M, Su, S, Gouil, Q, Diakumis, P, Bahlo, M, Sargeant, T, Kats, LM, Hodgkin, PD, O'Keeffe, M, Ng, AP, Ritchie, ME & Naik, SH 2021, 'Clonal multi-omics reveals Bcor as a negative regulator of emergency dendritic cell development', Immunity, vol. 54, no. 6, pp. 1338-1351.e9. https://doi.org/10.1016/j.immuni.2021.03.012

TY - JOUR

T1 - Clonal multi-omics reveals Bcor as a negative regulator of emergency dendritic cell development

AU - Tian, Luyi

AU - Tomei, Sara

AU - Schreuder, Jaring

AU - Weber, Tom S.

AU - Amann-Zalcenstein, Daniela

AU - Lin, Dawn S.

AU - Tran, Jessica

AU - Audiger, Cindy

AU - Chu, Mathew

AU - Jarratt, Andrew

AU - Willson, Tracy

AU - Hilton, Adrienne

AU - Pang, Ee Shan

AU - Patton, Timothy

AU - Kelly, Madison

AU - Su, Shian

AU - Gouil, Quentin

AU - Diakumis, Peter

AU - Bahlo, Melanie

AU - Sargeant, Toby

AU - Kats, Lev M.

AU - Hodgkin, Philip D.

AU - O'Keeffe, Meredith

AU - Ng, Ashley P.

AU - Ritchie, Matthew E.

AU - Naik, Shalin H.

N1 - Funding Information: We thank WEHI core facilities, including Bioservices, Centre for Dynamic Imaging, Flow cytometry, and Genomics; D. Hilton, M. Blewitt, S. Nutt, S. Taoudi, and J. Powell for critical reading of the manuscript; and J.-G. Zhang for Flt3L. This work was supported by grants from the National Health and Medical Research Council , Australia ( GNT1062820 , GNT1100033 , GNT1101378 , GNT1124812 , and GNT1145184 ), and the Australia Research Council ’s special initiative Stem Cells Australia. Publisher Copyright: © 2021 Elsevier Inc.

PY - 2021/6/8

Y1 - 2021/6/8

N2 - Despite advances in single-cell multi-omics, a single stem or progenitor cell can only be tested once. We developed clonal multi-omics, in which daughters of a clone act as surrogates of the founder, thereby allowing multiple independent assays per clone. With SIS-seq, clonal siblings in parallel “sister” assays are examined either for gene expression by RNA sequencing (RNA-seq) or for fate in culture. We identified, and then validated using CRISPR, genes that controlled fate bias for different dendritic cell (DC) subtypes. This included Bcor as a suppressor of plasmacytoid DC (pDC) and conventional DC type 2 (cDC2) numbers during Flt3 ligand-mediated emergency DC development. We then developed SIS-skew to examine development of wild-type and Bcor-deficient siblings of the same clone in parallel. We found Bcor restricted clonal expansion, especially for cDC2s, and suppressed clonal fate potential, especially for pDCs. Therefore, SIS-seq and SIS-skew can reveal the molecular and cellular mechanisms governing clonal fate.

AB - Despite advances in single-cell multi-omics, a single stem or progenitor cell can only be tested once. We developed clonal multi-omics, in which daughters of a clone act as surrogates of the founder, thereby allowing multiple independent assays per clone. With SIS-seq, clonal siblings in parallel “sister” assays are examined either for gene expression by RNA sequencing (RNA-seq) or for fate in culture. We identified, and then validated using CRISPR, genes that controlled fate bias for different dendritic cell (DC) subtypes. This included Bcor as a suppressor of plasmacytoid DC (pDC) and conventional DC type 2 (cDC2) numbers during Flt3 ligand-mediated emergency DC development. We then developed SIS-skew to examine development of wild-type and Bcor-deficient siblings of the same clone in parallel. We found Bcor restricted clonal expansion, especially for cDC2s, and suppressed clonal fate potential, especially for pDCs. Therefore, SIS-seq and SIS-skew can reveal the molecular and cellular mechanisms governing clonal fate.

KW - cellular barcoding

KW - clonal lineage tracing

KW - CRISPR minipool

KW - dendritic cell

KW - Flt3 ligand

KW - immunotherapy

KW - single-cell fate

KW - single-cell RNA-seq

KW - state-fate

UR - http://www.scopus.com/inward/record.url?scp=85104952340&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2021.03.012

DO - 10.1016/j.immuni.2021.03.012

M3 - Article

C2 - 33862015

AN - SCOPUS:85104952340

SN - 1074-7613

VL - 54

SP - 1338-1351.e9

JO - Immunity

JF - Immunity

IS - 6

ER -

Clonal multi-omics reveals Bcor as a negative regulator of emergency dendritic cell development

Abstract

Keywords

UN SDGs

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