PMID- 29844206
OWN - NLM
STAT- MEDLINE
DCOM- 20190305
LR  - 20200306
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 2
IP  - 11
DP  - 2018 Jun 12
TI  - Activation of the vitamin D receptor transcription factor stimulates the growth 
      of definitive erythroid progenitors.
PG  - 1207-1219
LID - 10.1182/bloodadvances.2018017533 [doi]
AB  - The pathways that regulate the growth of erythroid progenitors are incompletely 
      understood. In a computational analysis of gene expression changes during 
      erythroid ontogeny, the vitamin D receptor (Vdr) nuclear hormone receptor 
      transcription factor gene was identified in fetal and adult stages, but not at 
      the embryonic stage of development. Vdr was expressed in definitive erythroid 
      (EryD) progenitors and was downregulated during their maturation. Activation of 
      Vdr signaling by the vitamin D3 agonist calcitriol increased the outgrowth of 
      EryD colonies from fetal liver and adult bone marrow, maintained progenitor 
      potential, and delayed erythroid maturation, as revealed by clonogenic assays, 
      suspension culture, cell surface phenotype, and gene expression analyses. The 
      early (cKit(+)CD71(lo/neg)), but not the late (cKit(+)CD71(hi)), EryD progenitor 
      subset of Lin(neg)cKit(+) cells was responsive to calcitriol. Culture of 
      cKit(+)CD71(lo/neg) progenitors in the presence of both vitamin D3 and 
      glucocorticoid receptor ligands resulted in an increase in proliferation that was 
      at least additive compared with either ligand alone. Lentivirus shRNA-mediated 
      knockdown of Vdr expression abrogated the stimulation of early erythroid 
      progenitor growth by calcitriol. These findings suggest that Vdr has a 
      cell-intrinsic function in early erythroid progenitors. Targeting of downstream 
      components of the Vdr signaling pathway may lead to new approaches for the 
      expansion of erythroid progenitors ex vivo.
CI  - (c) 2018 by The American Society of Hematology.
FAU - Barminko, Jeffrey
AU  - Barminko J
AD  - Department of Medicine.
AD  - The Tisch Cancer Institute.
FAU - Reinholt, Brad M
AU  - Reinholt BM
AD  - Department of Medicine.
AD  - The Tisch Cancer Institute.
FAU - Emmanuelli, Alexander
AU  - Emmanuelli A
AD  - Department of Medicine.
AD  - The Tisch Cancer Institute.
FAU - Lejeune, Alannah N
AU  - Lejeune AN
AD  - Department of Medicine.
AD  - The Tisch Cancer Institute.
FAU - Baron, Margaret H
AU  - Baron MH
AD  - Department of Medicine.
AD  - The Tisch Cancer Institute.
AD  - Department of Cellular, Developmental and Regenerative Biology.
AD  - Department of Oncological Sciences, and.
AD  - The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, 
      New York, NY.
LA  - eng
GR  - R01 DK052191/DK/NIDDK NIH HHS/United States
GR  - R01 DK102945/DK/NIDDK NIH HHS/United States
GR  - R01 HL062248/HL/NHLBI NIH HHS/United States
GR  - T32 HL094283/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (Receptors, Calcitriol)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - Animals
MH  - Calcitriol/*pharmacology
MH  - Embryo, Mammalian/cytology/*metabolism
MH  - Erythroid Precursor Cells/cytology/*metabolism
MH  - Gene Expression Regulation, Developmental/*drug effects/physiology
MH  - Mice
MH  - Receptors, Calcitriol/agonists/*metabolism
PMC - PMC5998938
COIS- Conflict-of-interest disclosure: The authors declare no competing financial 
      interests.
EDAT- 2018/05/31 06:00
MHDA- 2019/03/06 06:00
PMCR- 2018/05/29
CRDT- 2018/05/31 06:00
PHST- 2018/02/28 00:00 [received]
PHST- 2018/04/15 00:00 [accepted]
PHST- 2018/05/31 06:00 [entrez]
PHST- 2018/05/31 06:00 [pubmed]
PHST- 2019/03/06 06:00 [medline]
PHST- 2018/05/29 00:00 [pmc-release]
AID - bloodadvances.2018017533 [pii]
AID - 2018/017533 [pii]
AID - 10.1182/bloodadvances.2018017533 [doi]
PST - ppublish
SO  - Blood Adv. 2018 Jun 12;2(11):1207-1219. doi: 10.1182/bloodadvances.2018017533.