Engraftment and Reconstitution of Hematopoiesis Is Dependent on VEGFR2-Mediated Regeneration of Sinusoidal Endothelial Cells

Research output: Contribution to journalArticle

Andrea T. Hooper, Jason M. Butler, Daniel J. Nolan, Andrea Kranz, Kaoruko Iida, Mariko Kobayashi, Hans Georg Kopp, Koji Shido, Isabelle Petit, Kilangsungla Yanger, Daylon James, Larry Witte, Zhenping Zhu, Yan Wu, Bronislaw Pytowski, Zev Rosenwaks, Vivek Mittal, Thomas N. Sato, Shahin Rafii

Myelosuppression damages the bone marrow (BM) vascular niche, but it is unclear how regeneration of bone marrow vessels contributes to engraftment of transplanted hematopoietic stem and progenitor cells (HSPCs) and restoration of hematopoiesis. We found that chemotherapy and sublethal irradiation induced minor regression of BM sinusoidal endothelial cells (SECs), while lethal irradiation induced severe regression of SECs and required BM transplantation (BMT) for regeneration. Within the BM, VEGFR2 expression specifically demarcated a continuous network of arterioles and SECs, with arterioles uniquely expressing Sca1 and SECs uniquely expressing VEGFR3. Conditional deletion of VEGFR2 in adult mice blocked regeneration of SECs in sublethally irradiated animals and prevented hematopoietic reconstitution. Similarly, inhibition of VEGFR2 signaling in lethally irradiated wild-type mice rescued with BMT severely impaired SEC reconstruction and prevented engraftment and reconstitution of HSPCs. Therefore, regeneration of SECs via VEGFR2 signaling is essential for engraftment of HSPCs and restoration of hematopoiesis.

Original languageEnglish
Pages (from-to)263-274
Number of pages12
JournalCell Stem Cell
Volume4
Issue number3
DOIs
StatePublished - Mar 6 2009

PMID: 19265665

PMCID: PMC3228275

Altmetrics

Cite this

Standard

Engraftment and Reconstitution of Hematopoiesis Is Dependent on VEGFR2-Mediated Regeneration of Sinusoidal Endothelial Cells. / Hooper, Andrea T.; Butler, Jason M.; Nolan, Daniel J.; Kranz, Andrea; Iida, Kaoruko; Kobayashi, Mariko; Kopp, Hans Georg; Shido, Koji; Petit, Isabelle; Yanger, Kilangsungla; James, Daylon; Witte, Larry; Zhu, Zhenping; Wu, Yan; Pytowski, Bronislaw; Rosenwaks, Zev; Mittal, Vivek; Sato, Thomas N.; Rafii, Shahin.

In: Cell Stem Cell, Vol. 4, No. 3, 06.03.2009, p. 263-274.

Research output: Contribution to journalArticle

Harvard

Hooper, AT, Butler, JM, Nolan, DJ, Kranz, A, Iida, K, Kobayashi, M, Kopp, HG, Shido, K, Petit, I, Yanger, K, James, D, Witte, L, Zhu, Z, Wu, Y, Pytowski, B, Rosenwaks, Z, Mittal, V, Sato, TN & Rafii, S 2009, 'Engraftment and Reconstitution of Hematopoiesis Is Dependent on VEGFR2-Mediated Regeneration of Sinusoidal Endothelial Cells' Cell Stem Cell, vol. 4, no. 3, pp. 263-274. https://doi.org/10.1016/j.stem.2009.01.006

APA

Hooper, A. T., Butler, J. M., Nolan, D. J., Kranz, A., Iida, K., Kobayashi, M., ... Rafii, S. (2009). Engraftment and Reconstitution of Hematopoiesis Is Dependent on VEGFR2-Mediated Regeneration of Sinusoidal Endothelial Cells. Cell Stem Cell, 4(3), 263-274. https://doi.org/10.1016/j.stem.2009.01.006

Vancouver

Hooper AT, Butler JM, Nolan DJ, Kranz A, Iida K, Kobayashi M et al. Engraftment and Reconstitution of Hematopoiesis Is Dependent on VEGFR2-Mediated Regeneration of Sinusoidal Endothelial Cells. Cell Stem Cell. 2009 Mar 6;4(3):263-274. https://doi.org/10.1016/j.stem.2009.01.006

Author

Hooper, Andrea T. ; Butler, Jason M. ; Nolan, Daniel J. ; Kranz, Andrea ; Iida, Kaoruko ; Kobayashi, Mariko ; Kopp, Hans Georg ; Shido, Koji ; Petit, Isabelle ; Yanger, Kilangsungla ; James, Daylon ; Witte, Larry ; Zhu, Zhenping ; Wu, Yan ; Pytowski, Bronislaw ; Rosenwaks, Zev ; Mittal, Vivek ; Sato, Thomas N. ; Rafii, Shahin. / Engraftment and Reconstitution of Hematopoiesis Is Dependent on VEGFR2-Mediated Regeneration of Sinusoidal Endothelial Cells. In: Cell Stem Cell. 2009 ; Vol. 4, No. 3. pp. 263-274.

BibTeX

@article{9729d267f66a4855a2ffc3354eb09823,
title = "Engraftment and Reconstitution of Hematopoiesis Is Dependent on VEGFR2-Mediated Regeneration of Sinusoidal Endothelial Cells",
abstract = "Myelosuppression damages the bone marrow (BM) vascular niche, but it is unclear how regeneration of bone marrow vessels contributes to engraftment of transplanted hematopoietic stem and progenitor cells (HSPCs) and restoration of hematopoiesis. We found that chemotherapy and sublethal irradiation induced minor regression of BM sinusoidal endothelial cells (SECs), while lethal irradiation induced severe regression of SECs and required BM transplantation (BMT) for regeneration. Within the BM, VEGFR2 expression specifically demarcated a continuous network of arterioles and SECs, with arterioles uniquely expressing Sca1 and SECs uniquely expressing VEGFR3. Conditional deletion of VEGFR2 in adult mice blocked regeneration of SECs in sublethally irradiated animals and prevented hematopoietic reconstitution. Similarly, inhibition of VEGFR2 signaling in lethally irradiated wild-type mice rescued with BMT severely impaired SEC reconstruction and prevented engraftment and reconstitution of HSPCs. Therefore, regeneration of SECs via VEGFR2 signaling is essential for engraftment of HSPCs and restoration of hematopoiesis.",
keywords = "STEMCELL",
author = "Hooper, {Andrea T.} and Butler, {Jason M.} and Nolan, {Daniel J.} and Andrea Kranz and Kaoruko Iida and Mariko Kobayashi and Kopp, {Hans Georg} and Koji Shido and Isabelle Petit and Kilangsungla Yanger and Daylon James and Larry Witte and Zhenping Zhu and Yan Wu and Bronislaw Pytowski and Zev Rosenwaks and Vivek Mittal and Sato, {Thomas N.} and Shahin Rafii",
year = "2009",
month = "3",
day = "6",
doi = "10.1016/j.stem.2009.01.006",
language = "English",
volume = "4",
pages = "263--274",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "3",

}

RIS

TY - JOUR

T1 - Engraftment and Reconstitution of Hematopoiesis Is Dependent on VEGFR2-Mediated Regeneration of Sinusoidal Endothelial Cells

AU - Hooper, Andrea T.

AU - Butler, Jason M.

AU - Nolan, Daniel J.

AU - Kranz, Andrea

AU - Iida, Kaoruko

AU - Kobayashi, Mariko

AU - Kopp, Hans Georg

AU - Shido, Koji

AU - Petit, Isabelle

AU - Yanger, Kilangsungla

AU - James, Daylon

AU - Witte, Larry

AU - Zhu, Zhenping

AU - Wu, Yan

AU - Pytowski, Bronislaw

AU - Rosenwaks, Zev

AU - Mittal, Vivek

AU - Sato, Thomas N.

AU - Rafii, Shahin

PY - 2009/3/6

Y1 - 2009/3/6

N2 - Myelosuppression damages the bone marrow (BM) vascular niche, but it is unclear how regeneration of bone marrow vessels contributes to engraftment of transplanted hematopoietic stem and progenitor cells (HSPCs) and restoration of hematopoiesis. We found that chemotherapy and sublethal irradiation induced minor regression of BM sinusoidal endothelial cells (SECs), while lethal irradiation induced severe regression of SECs and required BM transplantation (BMT) for regeneration. Within the BM, VEGFR2 expression specifically demarcated a continuous network of arterioles and SECs, with arterioles uniquely expressing Sca1 and SECs uniquely expressing VEGFR3. Conditional deletion of VEGFR2 in adult mice blocked regeneration of SECs in sublethally irradiated animals and prevented hematopoietic reconstitution. Similarly, inhibition of VEGFR2 signaling in lethally irradiated wild-type mice rescued with BMT severely impaired SEC reconstruction and prevented engraftment and reconstitution of HSPCs. Therefore, regeneration of SECs via VEGFR2 signaling is essential for engraftment of HSPCs and restoration of hematopoiesis.

AB - Myelosuppression damages the bone marrow (BM) vascular niche, but it is unclear how regeneration of bone marrow vessels contributes to engraftment of transplanted hematopoietic stem and progenitor cells (HSPCs) and restoration of hematopoiesis. We found that chemotherapy and sublethal irradiation induced minor regression of BM sinusoidal endothelial cells (SECs), while lethal irradiation induced severe regression of SECs and required BM transplantation (BMT) for regeneration. Within the BM, VEGFR2 expression specifically demarcated a continuous network of arterioles and SECs, with arterioles uniquely expressing Sca1 and SECs uniquely expressing VEGFR3. Conditional deletion of VEGFR2 in adult mice blocked regeneration of SECs in sublethally irradiated animals and prevented hematopoietic reconstitution. Similarly, inhibition of VEGFR2 signaling in lethally irradiated wild-type mice rescued with BMT severely impaired SEC reconstruction and prevented engraftment and reconstitution of HSPCs. Therefore, regeneration of SECs via VEGFR2 signaling is essential for engraftment of HSPCs and restoration of hematopoiesis.

KW - STEMCELL

UR - http://www.scopus.com/inward/record.url?scp=60849138787&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=60849138787&partnerID=8YFLogxK

U2 - 10.1016/j.stem.2009.01.006

DO - 10.1016/j.stem.2009.01.006

M3 - Article

VL - 4

SP - 263

EP - 274

JO - Cell Stem Cell

T2 - Cell Stem Cell

JF - Cell Stem Cell

SN - 1934-5909

IS - 3

ER -

ID: 3371407