PMID- 32442338
OWN - NLM
STAT- MEDLINE
DCOM- 20210701
LR  - 20210701
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Linking)
VI  - 38
IP  - 9
DP  - 2020 Sep
TI  - Ubiquitous overexpression of CXCL12 confers radiation protection and enhances 
      mobilization of hematopoietic stem and progenitor cells.
PG  - 1159-1174
LID - 10.1002/stem.3205 [doi]
AB  - C-X-C motif chemokine ligand 12 (CXCL12; aka SDF1alpha) is a major regulator of a 
      number of cellular systems, including hematopoiesis, where it influences 
      hematopoietic cell trafficking, proliferation, and survival during homeostasis 
      and upon stress and disease. A variety of constitutive, temporal, ubiquitous, and 
      cell-specific loss-of-function models have documented the functional consequences 
      on hematopoiesis upon deletion of Cxcl12. Here, in contrast to loss-of-function 
      experiments, we implemented a gain-of-function approach by generating a 
      doxycycline-inducible transgenic mouse model that enables spatial and temporal 
      overexpression of Cxcl12. We demonstrated that ubiquitous CXCL12 overexpression 
      led to an increase in multipotent progenitors in the bone marrow and spleen. The 
      CXCL12+ mice displayed reduced reconstitution potential as either donors or 
      recipients in transplantation experiments. Additionally, we discovered that 
      Cxcl12 overexpression improved hematopoietic stem and progenitor cell 
      mobilization into the blood, and conferred radioprotection by promoting 
      quiescence. Thus, this new CXCL12+ mouse model provided new insights into major 
      facets of hematopoiesis and serves as a versatile resource for studying CXCL12 
      function in a variety of contexts.
CI  - (c) AlphaMed Press 2020.
FAU - Rajendiran, Smrithi
AU  - Rajendiran S
AUID- ORCID: 0000-0001-5259-2579
AD  - Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, 
      University of California Santa Cruz, Santa Cruz, California, USA.
FAU - Smith-Berdan, Stephanie
AU  - Smith-Berdan S
AD  - Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, 
      University of California Santa Cruz, Santa Cruz, California, USA.
FAU - Kunz, Leo
AU  - Kunz L
AD  - Department of Biosystems Science and Engineering, Eidgenossische Technische 
      Hochschule Zurich, Basel, Switzerland.
FAU - Risolino, Maurizio
AU  - Risolino M
AD  - Program in Craniofacial Biology, Institute of Human Genetics, Eli and Edyth Broad 
      Center of Regeneration Medicine and Stem Cell Research, Departments of Orofacial 
      Sciences and Anatomy, University of California, San Francisco, California, USA.
FAU - Selleri, Licia
AU  - Selleri L
AD  - Program in Craniofacial Biology, Institute of Human Genetics, Eli and Edyth Broad 
      Center of Regeneration Medicine and Stem Cell Research, Departments of Orofacial 
      Sciences and Anatomy, University of California, San Francisco, California, USA.
FAU - Schroeder, Timm
AU  - Schroeder T
AD  - Department of Biosystems Science and Engineering, Eidgenossische Technische 
      Hochschule Zurich, Basel, Switzerland.
FAU - Forsberg, E Camilla
AU  - Forsberg EC
AUID- ORCID: 0000-0002-8740-4299
AD  - Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, 
      University of California Santa Cruz, Santa Cruz, California, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200620
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Benzylamines)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Cyclams)
RN  - S915P5499N (plerixafor)
SB  - IM
MH  - Animals
MH  - Benzylamines/pharmacology
MH  - Bone Marrow Cells/drug effects/metabolism
MH  - Cell Count
MH  - Cell Cycle/drug effects
MH  - Chemokine CXCL12/*metabolism
MH  - Cyclams/pharmacology
MH  - *Hematopoietic Stem Cell Mobilization
MH  - Hematopoietic Stem Cell Transplantation
MH  - Hematopoietic Stem Cells/drug effects/*metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Multipotent Stem Cells/cytology/drug effects/metabolism
MH  - Neovascularization, Physiologic/drug effects
MH  - *Radiation Protection
OTO - NOTNLM
OT  - CXCL12 transgenic
OT  - hematopoiesis
OT  - hematopoietic stem cells
OT  - mobilization
OT  - radiation protection
EDAT- 2020/05/23 06:00
MHDA- 2021/07/02 06:00
CRDT- 2020/05/23 06:00
PHST- 2020/01/09 00:00 [received]
PHST- 2020/04/16 00:00 [accepted]
PHST- 2020/05/23 06:00 [pubmed]
PHST- 2021/07/02 06:00 [medline]
PHST- 2020/05/23 06:00 [entrez]
AID - 10.1002/stem.3205 [doi]
PST - ppublish
SO  - Stem Cells. 2020 Sep;38(9):1159-1174. doi: 10.1002/stem.3205. Epub 2020 Jun 20.