Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics

Brandon Hadland; Barbara Varnum-Finney; Stacey Dozono; Tessa Dignum; Cynthia Nourigat-McKay; Adam M. Heck; Takashi Ishida; Dana L. Jackson; Tomer Itkin; Jason M. Butler; Shahin Rafii; Cole Trapnell; Irwin D. Bernstein

doi:10.1038/s41467-022-28781-z

Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics

Brandon Hadland, Barbara Varnum-Finney, Stacey Dozono, Tessa Dignum, Cynthia Nourigat-McKay, Adam M. Heck, Takashi Ishida, Dana L. Jackson, Tomer Itkin, Jason M. Butler, Shahin Rafii, Cole Trapnell, Irwin D. Bernstein

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

Abstract

Hematopoietic stem cells (HSCs) develop from hemogenic endothelium within embryonic arterial vessels such as the aorta of the aorta-gonad-mesonephros region (AGM). To identify the signals responsible for HSC formation, here we use single cell RNA-sequencing to simultaneously analyze the transcriptional profiles of AGM-derived cells transitioning from hemogenic endothelium to HSCs, and AGM-derived endothelial cells which provide signals sufficient to support HSC maturation and self-renewal. Pseudotemporal ordering reveals dynamics of gene expression during the hemogenic endothelium to HSC transition, identifying surface receptors specifically expressed on developing HSCs. Transcriptional profiling of niche endothelial cells identifies corresponding ligands, including those signaling to Notch receptors, VLA-4 integrin, and CXCR4, which, when integrated in an engineered platform, are sufficient to support the generation of engrafting HSCs. These studies provide a transcriptional map of the signaling interactions necessary for the development of HSCs and advance the goal of engineering HSCs for therapeutic applications.

Original language	English
Article number	1584
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-28781-z
State	Published - Dec 2022
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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Hadland, B., Varnum-Finney, B., Dozono, S., Dignum, T., Nourigat-McKay, C., Heck, A. M., Ishida, T., Jackson, D. L., Itkin, T., Butler, J. M., Rafii, S., Trapnell, C., & Bernstein, I. D. (2022). Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics. Nature Communications, 13(1), Article 1584. https://doi.org/10.1038/s41467-022-28781-z

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title = "Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics",

abstract = "Hematopoietic stem cells (HSCs) develop from hemogenic endothelium within embryonic arterial vessels such as the aorta of the aorta-gonad-mesonephros region (AGM). To identify the signals responsible for HSC formation, here we use single cell RNA-sequencing to simultaneously analyze the transcriptional profiles of AGM-derived cells transitioning from hemogenic endothelium to HSCs, and AGM-derived endothelial cells which provide signals sufficient to support HSC maturation and self-renewal. Pseudotemporal ordering reveals dynamics of gene expression during the hemogenic endothelium to HSC transition, identifying surface receptors specifically expressed on developing HSCs. Transcriptional profiling of niche endothelial cells identifies corresponding ligands, including those signaling to Notch receptors, VLA-4 integrin, and CXCR4, which, when integrated in an engineered platform, are sufficient to support the generation of engrafting HSCs. These studies provide a transcriptional map of the signaling interactions necessary for the development of HSCs and advance the goal of engineering HSCs for therapeutic applications.",

author = "Brandon Hadland and Barbara Varnum-Finney and Stacey Dozono and Tessa Dignum and Cynthia Nourigat-McKay and Heck, {Adam M.} and Takashi Ishida and Jackson, {Dana L.} and Tomer Itkin and Butler, {Jason M.} and Shahin Rafii and Cole Trapnell and Bernstein, {Irwin D.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

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doi = "10.1038/s41467-022-28781-z",

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Hadland, B, Varnum-Finney, B, Dozono, S, Dignum, T, Nourigat-McKay, C, Heck, AM, Ishida, T, Jackson, DL, Itkin, T, Butler, JM, Rafii, S, Trapnell, C & Bernstein, ID 2022, 'Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics', Nature Communications, vol. 13, no. 1, 1584. https://doi.org/10.1038/s41467-022-28781-z

TY - JOUR

T1 - Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics

AU - Hadland, Brandon

AU - Varnum-Finney, Barbara

AU - Dozono, Stacey

AU - Dignum, Tessa

AU - Nourigat-McKay, Cynthia

AU - Heck, Adam M.

AU - Ishida, Takashi

AU - Jackson, Dana L.

AU - Itkin, Tomer

AU - Butler, Jason M.

AU - Rafii, Shahin

AU - Trapnell, Cole

AU - Bernstein, Irwin D.

PY - 2022/12

Y1 - 2022/12

N2 - Hematopoietic stem cells (HSCs) develop from hemogenic endothelium within embryonic arterial vessels such as the aorta of the aorta-gonad-mesonephros region (AGM). To identify the signals responsible for HSC formation, here we use single cell RNA-sequencing to simultaneously analyze the transcriptional profiles of AGM-derived cells transitioning from hemogenic endothelium to HSCs, and AGM-derived endothelial cells which provide signals sufficient to support HSC maturation and self-renewal. Pseudotemporal ordering reveals dynamics of gene expression during the hemogenic endothelium to HSC transition, identifying surface receptors specifically expressed on developing HSCs. Transcriptional profiling of niche endothelial cells identifies corresponding ligands, including those signaling to Notch receptors, VLA-4 integrin, and CXCR4, which, when integrated in an engineered platform, are sufficient to support the generation of engrafting HSCs. These studies provide a transcriptional map of the signaling interactions necessary for the development of HSCs and advance the goal of engineering HSCs for therapeutic applications.

AB - Hematopoietic stem cells (HSCs) develop from hemogenic endothelium within embryonic arterial vessels such as the aorta of the aorta-gonad-mesonephros region (AGM). To identify the signals responsible for HSC formation, here we use single cell RNA-sequencing to simultaneously analyze the transcriptional profiles of AGM-derived cells transitioning from hemogenic endothelium to HSCs, and AGM-derived endothelial cells which provide signals sufficient to support HSC maturation and self-renewal. Pseudotemporal ordering reveals dynamics of gene expression during the hemogenic endothelium to HSC transition, identifying surface receptors specifically expressed on developing HSCs. Transcriptional profiling of niche endothelial cells identifies corresponding ligands, including those signaling to Notch receptors, VLA-4 integrin, and CXCR4, which, when integrated in an engineered platform, are sufficient to support the generation of engrafting HSCs. These studies provide a transcriptional map of the signaling interactions necessary for the development of HSCs and advance the goal of engineering HSCs for therapeutic applications.

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DO - 10.1038/s41467-022-28781-z

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SN - 2041-1723

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JO - Nature Communications

JF - Nature Communications

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ER -

Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics

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