Neuropilin 1 regulates bone marrow vascular regeneration and hematopoietic reconstitution

Christina M. Termini, Amara Pang, Tiancheng Fang, Martina Roos, Vivian Y. Chang, Yurun Zhang, Nicollette J. Setiawan, Lia Signaevskaia, Michelle Li, Mindy M. Kim, Orel Tabibi, Paulina K. Lin, Joshua P. Sasine, Avradip Chatterjee, Ramachandran Murali, Heather A. Himburg and John P. Chute ()
Additional contact information
Christina M. Termini: University of California
Amara Pang: Cedars Sinai Medical Center
Tiancheng Fang: University of California
Martina Roos: University of California
Vivian Y. Chang: UCLA
Yurun Zhang: University of California
Nicollette J. Setiawan: Cedars Sinai Medical Center
Lia Signaevskaia: University of California
Michelle Li: University of California
Mindy M. Kim: University of California
Orel Tabibi: University of California
Paulina K. Lin: University of California
Joshua P. Sasine: University of California
Avradip Chatterjee: Research Division of Immunology
Ramachandran Murali: Research Division of Immunology
Heather A. Himburg: Medical College of Wisconsin
John P. Chute: Cedars Sinai Medical Center

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract Ionizing radiation and chemotherapy deplete hematopoietic stem cells and damage the vascular niche wherein hematopoietic stem cells reside. Hematopoietic stem cell regeneration requires signaling from an intact bone marrow (BM) vascular niche, but the mechanisms that control BM vascular niche regeneration are poorly understood. We report that BM vascular endothelial cells secrete semaphorin 3 A (SEMA3A) in response to myeloablation and SEMA3A induces p53 – mediated apoptosis in BM endothelial cells via signaling through its receptor, Neuropilin 1 (NRP1), and activation of cyclin dependent kinase 5. Endothelial cell – specific deletion of Nrp1 or Sema3a or administration of anti-NRP1 antibody suppresses BM endothelial cell apoptosis, accelerates BM vascular regeneration and concordantly drives hematopoietic reconstitution in irradiated mice. In response to NRP1 inhibition, BM endothelial cells increase expression and secretion of the Wnt signal amplifying protein, R spondin 2. Systemic administration of anti - R spondin 2 blocks HSC regeneration and hematopoietic reconstitution which otherwise occurrs in response to NRP1 inhibition. SEMA3A – NRP1 signaling promotes BM vascular regression following myelosuppression and therapeutic blockade of SEMA3A – NRP1 signaling in BM endothelial cells accelerates vascular and hematopoietic regeneration in vivo.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-27263-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27263-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-27263-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().