Endothelial Jagged-1 Is Necessary for Homeostatic and Regenerative Hematopoiesis
The bone marrow (BM) microenvironment is composed of multiple niche cells that, by producing paracrine factors, maintain and regenerate the hematopoietic stem cell (HSC) pool (Morrison and Spradling, 2008). We have previously demonstrated that endothelial cells support the proper regeneration of the...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2013-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713004105 |
| _version_ | 1811329279643877376 |
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| author | Michael G. Poulos Peipei Guo Natalie M. Kofler Sandra Pinho Michael C. Gutkin Anastasia Tikhonova Iannis Aifantis Paul S. Frenette Jan Kitajewski Shahin Rafii Jason M. Butler |
| author_facet | Michael G. Poulos Peipei Guo Natalie M. Kofler Sandra Pinho Michael C. Gutkin Anastasia Tikhonova Iannis Aifantis Paul S. Frenette Jan Kitajewski Shahin Rafii Jason M. Butler |
| author_sort | Michael G. Poulos |
| collection | DOAJ |
| description | The bone marrow (BM) microenvironment is composed of multiple niche cells that, by producing paracrine factors, maintain and regenerate the hematopoietic stem cell (HSC) pool (Morrison and Spradling, 2008). We have previously demonstrated that endothelial cells support the proper regeneration of the hematopoietic system following myeloablation (Butler et al., 2010; Hooper et al., 2009; Kobayashi et al., 2010). Here, we demonstrate that expression of the angiocrine factor Jagged-1, supplied by the BM vascular niche, regulates homeostatic and regenerative hematopoiesis through a Notch-dependent mechanism. Conditional deletion of Jagged-1 in endothelial cells (Jag1(ECKO) mice) results in a profound decrease in hematopoiesis and premature exhaustion of the adult HSC pool, whereas quantification and functional assays demonstrate that loss of Jagged-1 does not perturb vascular or mesenchymal compartments. Taken together, these data demonstrate that the instructive function of endothelial-specific Jagged-1 is required to support the self-renewal and regenerative capacity of HSCs in the adult BM vascular niche. |
| first_indexed | 2024-04-13T15:41:00Z |
| format | Article |
| id | doaj.art-a2de7d96b8d94890af4dc12d7b19d166 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T15:41:00Z |
| publishDate | 2013-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-a2de7d96b8d94890af4dc12d7b19d1662022-12-22T02:41:09ZengElsevierCell Reports2211-12472013-09-01451022103410.1016/j.celrep.2013.07.048Endothelial Jagged-1 Is Necessary for Homeostatic and Regenerative HematopoiesisMichael G. Poulos0Peipei Guo1Natalie M. Kofler2Sandra Pinho3Michael C. Gutkin4Anastasia Tikhonova5Iannis Aifantis6Paul S. Frenette7Jan Kitajewski8Shahin Rafii9Jason M. Butler10Department of Genetic Medicine, Ansary Stem Cell Instiute, Weill Cornell Medical College, New York, NY 10021, USADepartment of Genetic Medicine, Ansary Stem Cell Instiute, Weill Cornell Medical College, New York, NY 10021, USADepartment of OB/GYN, Columbia University Medical Center, New York, NY 10032, USARuth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, New York, NY 10461, USADepartment of Genetic Medicine, Ansary Stem Cell Instiute, Weill Cornell Medical College, New York, NY 10021, USAHoward Hughes Medical Institute and NYU Cancer Institute, NYU School of Medicine, New York, NY 10016, USAHoward Hughes Medical Institute and NYU Cancer Institute, NYU School of Medicine, New York, NY 10016, USARuth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, New York, NY 10461, USADepartment of OB/GYN, Columbia University Medical Center, New York, NY 10032, USADepartment of Genetic Medicine, Ansary Stem Cell Instiute, Weill Cornell Medical College, New York, NY 10021, USADepartment of Genetic Medicine, Ansary Stem Cell Instiute, Weill Cornell Medical College, New York, NY 10021, USAThe bone marrow (BM) microenvironment is composed of multiple niche cells that, by producing paracrine factors, maintain and regenerate the hematopoietic stem cell (HSC) pool (Morrison and Spradling, 2008). We have previously demonstrated that endothelial cells support the proper regeneration of the hematopoietic system following myeloablation (Butler et al., 2010; Hooper et al., 2009; Kobayashi et al., 2010). Here, we demonstrate that expression of the angiocrine factor Jagged-1, supplied by the BM vascular niche, regulates homeostatic and regenerative hematopoiesis through a Notch-dependent mechanism. Conditional deletion of Jagged-1 in endothelial cells (Jag1(ECKO) mice) results in a profound decrease in hematopoiesis and premature exhaustion of the adult HSC pool, whereas quantification and functional assays demonstrate that loss of Jagged-1 does not perturb vascular or mesenchymal compartments. Taken together, these data demonstrate that the instructive function of endothelial-specific Jagged-1 is required to support the self-renewal and regenerative capacity of HSCs in the adult BM vascular niche.http://www.sciencedirect.com/science/article/pii/S2211124713004105 |
| spellingShingle | Michael G. Poulos Peipei Guo Natalie M. Kofler Sandra Pinho Michael C. Gutkin Anastasia Tikhonova Iannis Aifantis Paul S. Frenette Jan Kitajewski Shahin Rafii Jason M. Butler Endothelial Jagged-1 Is Necessary for Homeostatic and Regenerative Hematopoiesis Cell Reports |
| title | Endothelial Jagged-1 Is Necessary for Homeostatic and Regenerative Hematopoiesis |
| title_full | Endothelial Jagged-1 Is Necessary for Homeostatic and Regenerative Hematopoiesis |
| title_fullStr | Endothelial Jagged-1 Is Necessary for Homeostatic and Regenerative Hematopoiesis |
| title_full_unstemmed | Endothelial Jagged-1 Is Necessary for Homeostatic and Regenerative Hematopoiesis |
| title_short | Endothelial Jagged-1 Is Necessary for Homeostatic and Regenerative Hematopoiesis |
| title_sort | endothelial jagged 1 is necessary for homeostatic and regenerative hematopoiesis |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713004105 |
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