Fate mapping and scRNA sequencing reveal origin and diversity of lymph node stromal precursors

Elisa Lenti; Luca Genovese; Silvia Bianchessi; Aurora Maurizio; Simona Baghai Sain; Alessia di Lillo; Greta Mattavelli; Itamar Harel; Francesca Bernassola; Thomas Hehlgans; Klaus Pfeffer; Mariacristina Crosti; Sergio Abrignani; Sylvia M. Evans; Giovanni Sitia; Nuno Guimarães-Camboa; Vincenzo Russo; Serge A. van de Pavert; Jose Manuel Garcia-Manteiga; Andrea Brendolan

doi:10.1016/j.immuni.2022.03.002

Fate mapping and scRNA sequencing reveal origin and diversity of lymph node stromal precursors

Elisa Lenti, Luca Genovese, Silvia Bianchessi, Aurora Maurizio, Simona Baghai Sain, Alessia di Lillo, Greta Mattavelli, Itamar Harel, Francesca Bernassola, Thomas Hehlgans, Klaus Pfeffer, Mariacristina Crosti, Sergio Abrignani, Sylvia M. Evans, Giovanni Sitia, Nuno Guimarães-Camboa, Vincenzo Russo, Serge A. van de Pavert, Jose Manuel Garcia-Manteiga, Andrea Brendolan^*

^*Corresponding author for this work

Department of Genetics

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

8 Scopus citations

Abstract

Lymph node (LN) stromal cells play a crucial role in LN development and in supporting adaptive immune responses. However, their origin, differentiation pathways, and transcriptional programs are still elusive. Here, we used lineage-tracing approaches and single-cell transcriptome analyses to determine origin, transcriptional profile, and composition of LN stromal and endothelial progenitors. Our results showed that all major stromal cell subsets and a large proportion of blood endothelial cells originate from embryonic Hoxb6⁺ progenitors of the lateral plate mesoderm (LPM), whereas lymphatic endothelial cells arise from Pax3⁺ progenitors of the paraxial mesoderm (PXM). Single-cell RNA sequencing revealed the existence of different Cd34⁺ and Cxcl13⁺ stromal cell subsets and showed that embryonic LNs contain proliferating progenitors possibly representing the amplifying populations for terminally differentiated cells. Taken together, our work identifies the earliest embryonic sources of LN stromal and endothelial cells and demonstrates that stromal diversity begins already during LN development.

Original language	English
Pages (from-to)	606-622.e6
Journal	Immunity
Volume	55
Issue number	4
DOIs	https://doi.org/10.1016/j.immuni.2022.03.002
State	Published - 12 Apr 2022

Bibliographical note

Publisher Copyright:
© 2022 Elsevier Inc.

Keywords

fibroblastic reticular cell
follicular dendritic cell
lineage tracing
lymph node development
marginal reticular cell
perivascular cell
single cell RNA-seq

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10.1016/j.immuni.2022.03.002

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Lenti, E., Genovese, L., Bianchessi, S., Maurizio, A., Sain, S. B., di Lillo, A., Mattavelli, G., Harel, I., Bernassola, F., Hehlgans, T., Pfeffer, K., Crosti, M., Abrignani, S., Evans, S. M., Sitia, G., Guimarães-Camboa, N., Russo, V., van de Pavert, S. A., Garcia-Manteiga, J. M., & Brendolan, A. (2022). Fate mapping and scRNA sequencing reveal origin and diversity of lymph node stromal precursors. Immunity, 55(4), 606-622.e6. https://doi.org/10.1016/j.immuni.2022.03.002

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title = "Fate mapping and scRNA sequencing reveal origin and diversity of lymph node stromal precursors",

abstract = "Lymph node (LN) stromal cells play a crucial role in LN development and in supporting adaptive immune responses. However, their origin, differentiation pathways, and transcriptional programs are still elusive. Here, we used lineage-tracing approaches and single-cell transcriptome analyses to determine origin, transcriptional profile, and composition of LN stromal and endothelial progenitors. Our results showed that all major stromal cell subsets and a large proportion of blood endothelial cells originate from embryonic Hoxb6+ progenitors of the lateral plate mesoderm (LPM), whereas lymphatic endothelial cells arise from Pax3+ progenitors of the paraxial mesoderm (PXM). Single-cell RNA sequencing revealed the existence of different Cd34+ and Cxcl13+ stromal cell subsets and showed that embryonic LNs contain proliferating progenitors possibly representing the amplifying populations for terminally differentiated cells. Taken together, our work identifies the earliest embryonic sources of LN stromal and endothelial cells and demonstrates that stromal diversity begins already during LN development.",

keywords = "fibroblastic reticular cell, follicular dendritic cell, lineage tracing, lymph node development, marginal reticular cell, perivascular cell, single cell RNA-seq",

author = "Elisa Lenti and Luca Genovese and Silvia Bianchessi and Aurora Maurizio and Sain, {Simona Baghai} and {di Lillo}, Alessia and Greta Mattavelli and Itamar Harel and Francesca Bernassola and Thomas Hehlgans and Klaus Pfeffer and Mariacristina Crosti and Sergio Abrignani and Evans, {Sylvia M.} and Giovanni Sitia and Nuno Guimar{\~a}es-Camboa and Vincenzo Russo and {van de Pavert}, {Serge A.} and Garcia-Manteiga, {Jose Manuel} and Andrea Brendolan",

note = "Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",

year = "2022",

month = apr,

day = "12",

doi = "10.1016/j.immuni.2022.03.002",

language = "אנגלית",

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Lenti, E, Genovese, L, Bianchessi, S, Maurizio, A, Sain, SB, di Lillo, A, Mattavelli, G, Harel, I, Bernassola, F, Hehlgans, T, Pfeffer, K, Crosti, M, Abrignani, S, Evans, SM, Sitia, G, Guimarães-Camboa, N, Russo, V, van de Pavert, SA, Garcia-Manteiga, JM & Brendolan, A 2022, 'Fate mapping and scRNA sequencing reveal origin and diversity of lymph node stromal precursors', Immunity, vol. 55, no. 4, pp. 606-622.e6. https://doi.org/10.1016/j.immuni.2022.03.002

TY - JOUR

T1 - Fate mapping and scRNA sequencing reveal origin and diversity of lymph node stromal precursors

AU - Lenti, Elisa

AU - Genovese, Luca

AU - Bianchessi, Silvia

AU - Maurizio, Aurora

AU - Sain, Simona Baghai

AU - di Lillo, Alessia

AU - Mattavelli, Greta

AU - Harel, Itamar

AU - Bernassola, Francesca

AU - Hehlgans, Thomas

AU - Pfeffer, Klaus

AU - Crosti, Mariacristina

AU - Abrignani, Sergio

AU - Evans, Sylvia M.

AU - Sitia, Giovanni

AU - Guimarães-Camboa, Nuno

AU - Russo, Vincenzo

AU - van de Pavert, Serge A.

AU - Garcia-Manteiga, Jose Manuel

AU - Brendolan, Andrea

PY - 2022/4/12

Y1 - 2022/4/12

N2 - Lymph node (LN) stromal cells play a crucial role in LN development and in supporting adaptive immune responses. However, their origin, differentiation pathways, and transcriptional programs are still elusive. Here, we used lineage-tracing approaches and single-cell transcriptome analyses to determine origin, transcriptional profile, and composition of LN stromal and endothelial progenitors. Our results showed that all major stromal cell subsets and a large proportion of blood endothelial cells originate from embryonic Hoxb6+ progenitors of the lateral plate mesoderm (LPM), whereas lymphatic endothelial cells arise from Pax3+ progenitors of the paraxial mesoderm (PXM). Single-cell RNA sequencing revealed the existence of different Cd34+ and Cxcl13+ stromal cell subsets and showed that embryonic LNs contain proliferating progenitors possibly representing the amplifying populations for terminally differentiated cells. Taken together, our work identifies the earliest embryonic sources of LN stromal and endothelial cells and demonstrates that stromal diversity begins already during LN development.

AB - Lymph node (LN) stromal cells play a crucial role in LN development and in supporting adaptive immune responses. However, their origin, differentiation pathways, and transcriptional programs are still elusive. Here, we used lineage-tracing approaches and single-cell transcriptome analyses to determine origin, transcriptional profile, and composition of LN stromal and endothelial progenitors. Our results showed that all major stromal cell subsets and a large proportion of blood endothelial cells originate from embryonic Hoxb6+ progenitors of the lateral plate mesoderm (LPM), whereas lymphatic endothelial cells arise from Pax3+ progenitors of the paraxial mesoderm (PXM). Single-cell RNA sequencing revealed the existence of different Cd34+ and Cxcl13+ stromal cell subsets and showed that embryonic LNs contain proliferating progenitors possibly representing the amplifying populations for terminally differentiated cells. Taken together, our work identifies the earliest embryonic sources of LN stromal and endothelial cells and demonstrates that stromal diversity begins already during LN development.

KW - fibroblastic reticular cell

KW - follicular dendritic cell

KW - lineage tracing

KW - lymph node development

KW - marginal reticular cell

KW - perivascular cell

KW - single cell RNA-seq

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U2 - 10.1016/j.immuni.2022.03.002

DO - 10.1016/j.immuni.2022.03.002

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C2 - 35358427

AN - SCOPUS:85127639305

SN - 1074-7613

VL - 55

SP - 606-622.e6

JO - Immunity

JF - Immunity

IS - 4

ER -

Fate mapping and scRNA sequencing reveal origin and diversity of lymph node stromal precursors

Abstract

Bibliographical note

Keywords

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