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 Sargeant

Lev 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

27 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

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

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

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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 - https://www.scopus.com/pages/publications/85104952340

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

UN SDGs

Keywords

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