PUBLICATION
Distinct Roles for Matrix Metalloproteinases 2 and 9 in Embryonic Hematopoietic Stem Cell Emergence, Migration, and Niche Colonization
- Authors
- Theodore, L.N., Hagedorn, E.J., Cortes, M., Natsuhara, K., Liu, S.Y., Perlin, J.R., Yang, S., Daily, M.L., Zon, L.I., North, T.E.
- ID
- ZDB-PUB-170419-6
- Date
- 2017
- Source
- Stem Cell Reports 8(5): 1226-1241 (Journal)
- Registered Authors
- North, Trista, Perlin, Julie, Zon, Leonard I.
- Keywords
- Cxcl12, HSC/HSPC, Mmp2, Mmp9, PGE(2), extracellular matrix, fibronectin, inflammation, zebrafish
- Datasets
- GEO:GSE93818
- MeSH Terms
-
- Animals
- Cell Movement*
- Cell Proliferation
- Chemokine CXCL12/metabolism
- Core Binding Factor Alpha 2 Subunit/metabolism
- Embryonic Stem Cells/cytology*
- Embryonic Stem Cells/metabolism
- Embryonic Stem Cells/physiology
- Extracellular Matrix/metabolism
- Fibronectins/metabolism
- Hematopoietic Stem Cells/cytology*
- Hematopoietic Stem Cells/metabolism
- Hematopoietic Stem Cells/physiology
- Matrix Metalloproteinase 2/genetics
- Matrix Metalloproteinase 2/metabolism*
- Matrix Metalloproteinase 9/genetics
- Matrix Metalloproteinase 9/metabolism*
- Stem Cell Niche*
- Zebrafish/embryology
- Zebrafish/metabolism
- Zebrafish Proteins/metabolism
- PubMed
- 28416284 Full text @ Stem Cell Reports
Citation
Theodore, L.N., Hagedorn, E.J., Cortes, M., Natsuhara, K., Liu, S.Y., Perlin, J.R., Yang, S., Daily, M.L., Zon, L.I., North, T.E. (2017) Distinct Roles for Matrix Metalloproteinases 2 and 9 in Embryonic Hematopoietic Stem Cell Emergence, Migration, and Niche Colonization. Stem Cell Reports. 8(5):1226-1241.
Abstract
Hematopoietic stem/progenitor cells (HSPCs) are formed during ontogeny from hemogenic endothelium in the ventral wall of the dorsal aorta (VDA). Critically, the cellular mechanism(s) allowing HSPC egress and migration to secondary niches are incompletely understood. Matrix metalloproteinases (MMPs) are inflammation-responsive proteins that regulate extracellular matrix (ECM) remodeling, cellular interactions, and signaling. Here, inhibition of vascular-associated Mmp2 function caused accumulation of fibronectin-rich ECM, retention of runx1/cmyb+ HSPCs in the VDA, and delayed caudal hematopoietic tissue (CHT) colonization; these defects were absent in fibronectin mutants, indicating that Mmp2 facilitates endothelial-to-hematopoietic transition via ECM remodeling. In contrast, Mmp9 was dispensable for HSPC budding, being instead required for proper colonization of secondary niches. Significantly, these migration defects were mimicked by overexpression and blocked by knockdown of C-X-C motif chemokine-12 (cxcl12), suggesting that Mmp9 controls CHT homeostasis through chemokine regulation. Our findings indicate Mmp2 and Mmp9 play distinct but complementary roles in developmental HSPC production and migration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping