PUBLICATION
Transcription factor induction of vascular blood stem cell niches in vivo
- Authors
- 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., Lichtig, A., Yang, S., Zhou, Y., Kunar, B., Gomez-Salinero, J.M., Dinh, T.T., Pan, J., Holler, K., Feldman, H.A., Butcher, E.C., van Oudenaarden, A., Rafii, S., Junker, J.P., Zon, L.I.
- ID
- ZDB-PUB-230430-39
- Date
- 2023
- Source
- Developmental Cell 58(12): 1037-1051.e4 (Journal)
- Registered Authors
- Zhou, Yi, Zon, Leonard I.
- Keywords
- blood stem cell niche, hematopoietic development, niche endothelial cells, reprogramming, vascular endothelium, zebrafish
- MeSH Terms
-
- Animals
- Endothelial Cells/metabolism
- Gene Expression Regulation
- Stem Cell Niche*
- Transcription Factors*/genetics
- Transcription Factors*/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 37119815 Full text @ Dev. Cell
Citation
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., Lichtig, A., Yang, S., Zhou, Y., Kunar, B., Gomez-Salinero, J.M., Dinh, T.T., Pan, J., Holler, K., Feldman, H.A., Butcher, E.C., van Oudenaarden, A., Rafii, S., Junker, J.P., Zon, L.I. (2023) Transcription factor induction of vascular blood stem cell niches in vivo. Developmental Cell. 58(12):1037-1051.e4.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping