Transcription factor induction of vascular blood stem cell niches in vivo

Elliott J Hagedorn; Julie R Perlin; Rebecca J Freeman; Samuel J Wattrus; Tianxiao Han; Clara Mao; Ji Wook Kim; Inés Fernández-Maestre; Madeleine L Daily; Christopher D'Amato; Michael J Fairchild; Raquel Riquelme; Brian Li; Dana A V E Ragoonanan; Khaliun Enkhbayar; Emily L Henault; Helen G Wang; Shelby E Redfield; Samantha H Collins; Asher Lichtig; Song Yang; Yi Zhou; Balvir Kunar; Jesus Maria Gomez-Salinero; Thanh T Dinh; Junliang Pan; Karoline Holler; Henry A Feldman; Eugene C Butcher; Alexander van Oudenaarden; Shahin Rafii; J Philipp Junker; Leonard I Zon

doi:10.1016/j.devcel.2023.04.007

Transcription factor induction of vascular blood stem cell niches in vivo

Elliott J Hagedorn, Julie R Perlin, Rebecca J Freeman, Samuel J Wattrus, Tianxiao Han, Clara Mao, Ji Wook Kim, Inés Fernández-Maestre, Madeleine L Daily, Christopher D'Amato, Michael J Fairchild, Raquel Riquelme, Brian Li, Dana A V E Ragoonanan, Khaliun Enkhbayar, Emily L Henault, Helen G Wang, Shelby E Redfield, Samantha H Collins, Asher LichtigSong Yang, Yi Zhou, Balvir Kunar, Jesus Maria Gomez-Salinero, Thanh T Dinh, Junliang Pan, Karoline Holler, Henry A Feldman, Eugene C Butcher, Alexander van Oudenaarden, Shahin Rafii, J Philipp Junker, Leonard I Zon

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

6 Citaten (Scopus)

Samenvatting

The hematopoietic niche is a supportive microenvironment composed of distinct cell types, including specialized vascular endothelial cells that directly interact with hematopoietic stem and progenitor cells (HSPCs). The molecular factors that specify niche endothelial cells and orchestrate HSPC homeostasis remain largely unknown. Using multi-dimensional gene expression and chromatin accessibility analyses in zebrafish, we define a conserved gene expression signature and cis-regulatory landscape that are unique to sinusoidal endothelial cells in the HSPC niche. Using enhancer mutagenesis and transcription factor overexpression, we elucidate a transcriptional code that involves members of the Ets, Sox, and nuclear hormone receptor families and is sufficient to induce ectopic niche endothelial cells that associate with mesenchymal stromal cells and support the recruitment, maintenance, and division of HSPCs in vivo. These studies set forth an approach for generating synthetic HSPC niches, in vitro or in vivo, and for effective therapies to modulate the endogenous niche.

Originele taal-2	Engels
Pagina's (van-tot)	1037-1051.e4
Tijdschrift	Developmental Cell
Volume	58
Nummer van het tijdschrift	12
DOI's	https://doi.org/10.1016/j.devcel.2023.04.007
Status	Gepubliceerd - 19 jun. 2023

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Hagedorn, E. J., Perlin, J. R., Freeman, R. J., Wattrus, S. J., Han, T., Mao, C., Kim, J. W., Fernández-Maestre, I., Daily, M. L., D'Amato, C., Fairchild, M. J., Riquelme, R., Li, B., Ragoonanan, D. A. V. E., Enkhbayar, K., Henault, E. L., Wang, H. G., Redfield, S. E., Collins, S. H., ... Zon, L. I. (2023). Transcription factor induction of vascular blood stem cell niches in vivo. Developmental Cell, 58(12), 1037-1051.e4. https://doi.org/10.1016/j.devcel.2023.04.007

@article{57b5a0542e664157aa1fee871017097f,

title = "Transcription factor induction of vascular blood stem cell niches in vivo",

abstract = "The hematopoietic niche is a supportive microenvironment composed of distinct cell types, including specialized vascular endothelial cells that directly interact with hematopoietic stem and progenitor cells (HSPCs). The molecular factors that specify niche endothelial cells and orchestrate HSPC homeostasis remain largely unknown. Using multi-dimensional gene expression and chromatin accessibility analyses in zebrafish, we define a conserved gene expression signature and cis-regulatory landscape that are unique to sinusoidal endothelial cells in the HSPC niche. Using enhancer mutagenesis and transcription factor overexpression, we elucidate a transcriptional code that involves members of the Ets, Sox, and nuclear hormone receptor families and is sufficient to induce ectopic niche endothelial cells that associate with mesenchymal stromal cells and support the recruitment, maintenance, and division of HSPCs in vivo. These studies set forth an approach for generating synthetic HSPC niches, in vitro or in vivo, and for effective therapies to modulate the endogenous niche.",

keywords = "Animals, Stem Cell Niche, Transcription Factors/genetics, Endothelial Cells/metabolism, Zebrafish/genetics, Gene Expression Regulation",

author = "Hagedorn, {Elliott J} and Perlin, {Julie R} and Freeman, {Rebecca J} and Wattrus, {Samuel J} and Tianxiao Han and Clara Mao and Kim, {Ji Wook} and In{\'e}s Fern{\'a}ndez-Maestre and Daily, {Madeleine L} and Christopher D'Amato and Fairchild, {Michael J} and Raquel Riquelme and Brian Li and Ragoonanan, {Dana A V E} and Khaliun Enkhbayar and Henault, {Emily L} and Wang, {Helen G} and Redfield, {Shelby E} and Collins, {Samantha H} and Asher Lichtig and Song Yang and Yi Zhou and Balvir Kunar and Gomez-Salinero, {Jesus Maria} and Dinh, {Thanh T} and Junliang Pan and Karoline Holler and Feldman, {Henry A} and Butcher, {Eugene C} and {van Oudenaarden}, Alexander and Shahin Rafii and Junker, {J Philipp} and Zon, {Leonard I}",

year = "2023",

month = jun,

day = "19",

doi = "10.1016/j.devcel.2023.04.007",

language = "English",

volume = "58",

pages = "1037--1051.e4",

journal = "Developmental Cell",

issn = "1534-5807",

publisher = "Cell Press",

number = "12",

}

Hagedorn, EJ, Perlin, JR, Freeman, RJ, Wattrus, SJ, Han, T, Mao, C, Kim, JW, Fernández-Maestre, I, Daily, ML, D'Amato, C, Fairchild, MJ, Riquelme, R, Li, B, Ragoonanan, DAVE, Enkhbayar, K, Henault, EL, Wang, HG, Redfield, SE, Collins, SH, Lichtig, A, Yang, S, Zhou, Y, Kunar, B, Gomez-Salinero, JM, Dinh, TT, Pan, J, Holler, K, Feldman, HA, Butcher, EC, van Oudenaarden, A, Rafii, S, Junker, JP & Zon, LI 2023, 'Transcription factor induction of vascular blood stem cell niches in vivo', Developmental Cell, vol. 58, nr. 12, blz. 1037-1051.e4. https://doi.org/10.1016/j.devcel.2023.04.007

TY - JOUR

T1 - Transcription factor induction of vascular blood stem cell niches in vivo

AU - Hagedorn, Elliott J

AU - Perlin, Julie R

AU - Freeman, Rebecca J

AU - Wattrus, Samuel J

AU - Han, Tianxiao

AU - Mao, Clara

AU - Kim, Ji Wook

AU - Fernández-Maestre, Inés

AU - Daily, Madeleine L

AU - D'Amato, Christopher

AU - Fairchild, Michael J

AU - Riquelme, Raquel

AU - Li, Brian

AU - Ragoonanan, Dana A V E

AU - Enkhbayar, Khaliun

AU - Henault, Emily L

AU - Wang, Helen G

AU - Redfield, Shelby E

AU - Collins, Samantha H

AU - Lichtig, Asher

AU - Yang, Song

AU - Zhou, Yi

AU - Kunar, Balvir

AU - Gomez-Salinero, Jesus Maria

AU - Dinh, Thanh T

AU - Pan, Junliang

AU - Holler, Karoline

AU - Feldman, Henry A

AU - Butcher, Eugene C

AU - van Oudenaarden, Alexander

AU - Rafii, Shahin

AU - Junker, J Philipp

AU - Zon, Leonard I

PY - 2023/6/19

Y1 - 2023/6/19

N2 - The hematopoietic niche is a supportive microenvironment composed of distinct cell types, including specialized vascular endothelial cells that directly interact with hematopoietic stem and progenitor cells (HSPCs). The molecular factors that specify niche endothelial cells and orchestrate HSPC homeostasis remain largely unknown. Using multi-dimensional gene expression and chromatin accessibility analyses in zebrafish, we define a conserved gene expression signature and cis-regulatory landscape that are unique to sinusoidal endothelial cells in the HSPC niche. Using enhancer mutagenesis and transcription factor overexpression, we elucidate a transcriptional code that involves members of the Ets, Sox, and nuclear hormone receptor families and is sufficient to induce ectopic niche endothelial cells that associate with mesenchymal stromal cells and support the recruitment, maintenance, and division of HSPCs in vivo. These studies set forth an approach for generating synthetic HSPC niches, in vitro or in vivo, and for effective therapies to modulate the endogenous niche.

AB - The hematopoietic niche is a supportive microenvironment composed of distinct cell types, including specialized vascular endothelial cells that directly interact with hematopoietic stem and progenitor cells (HSPCs). The molecular factors that specify niche endothelial cells and orchestrate HSPC homeostasis remain largely unknown. Using multi-dimensional gene expression and chromatin accessibility analyses in zebrafish, we define a conserved gene expression signature and cis-regulatory landscape that are unique to sinusoidal endothelial cells in the HSPC niche. Using enhancer mutagenesis and transcription factor overexpression, we elucidate a transcriptional code that involves members of the Ets, Sox, and nuclear hormone receptor families and is sufficient to induce ectopic niche endothelial cells that associate with mesenchymal stromal cells and support the recruitment, maintenance, and division of HSPCs in vivo. These studies set forth an approach for generating synthetic HSPC niches, in vitro or in vivo, and for effective therapies to modulate the endogenous niche.

KW - Animals

KW - Stem Cell Niche

KW - Transcription Factors/genetics

KW - Endothelial Cells/metabolism

KW - Zebrafish/genetics

KW - Gene Expression Regulation

U2 - 10.1016/j.devcel.2023.04.007

DO - 10.1016/j.devcel.2023.04.007

M3 - Article

C2 - 37119815

SN - 1534-5807

VL - 58

SP - 1037-1051.e4

JO - Developmental Cell

JF - Developmental Cell

IS - 12

ER -

Transcription factor induction of vascular blood stem cell niches in vivo

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