論文 - 詳細
| RRC ID | 51251 |
|---|---|
| 著者 | Theodore LN, Hagedorn EJ, Cortes M, Natsuhara K, Liu SY, Perlin JR, Yang S, Daily ML, Zon LI, North TE. |
| タイトル | Distinct Roles for Matrix Metalloproteinases 2 and 9 in Embryonic Hematopoietic Stem Cell Emergence, Migration, and Niche Colonization. |
| ジャーナル | Stem Cell Reports |
| 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. |
| 巻・号 | 8(5) |
| ページ | 1226-1241 |
| 公開日 | 2017-5-9 |
| DOI | 10.1016/j.stemcr.2017.03.016 |
| PII | S2213-6711(17)30122-4 |
| PMID | 28416284 |
| PMC | PMC5425629 |
| MeSH | 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 |
| IF | 6.032 |
| 引用数 | 20 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ゼブラフィッシュ | Tg(EF1α:mAG-zGem(1/100)) |