PMID- 9973316
OWN - NLM
STAT- MEDLINE
DCOM- 19990331
LR  - 20190516
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 13
IP  - 2
DP  - 1999 Feb
TI  - Oxygen tension modulates beta-globin switching in embryoid bodies.
PG  - 285-95
AB  - Little is known about the factors influencing the hemoglobin switch in 
      vertebrates during development. Inasmuch as the mammalian conceptus is exposed to 
      changing oxygen tensions in utero, we examined the effect of different oxygen 
      concentrations on beta-globin switching. We used an in vitro model of mouse 
      embryogenesis based on the differentiation of blastocyst-derived embryonic stem 
      cells to embryoid bodies (EBs). Cultivation of EBs at increasing oxygen 
      concentrations (starting at 1% O2) did not influence the temporal expression 
      pattern of embryonic (betaH1) globin compared to the normoxic controls (20% O2). 
      In contrast, when compared to normoxically grown EBs, expression of fetal/adult 
      (betamaj) globin in EBs cultured at varying oxygen concentrations was delayed by 
      about 2 days and persisted throughout differentiation. Quantitation of hemoglobin 
      in EBs using a 2,7-diaminofluorene-based colorimetric assay revealed the 
      appearence of hemoglobin in two waves, an early and a late one. This observation 
      was verified by spectrophotometric analysis of hemoglobin within single EBs. 
      These two waves might reflect the switch of erythropoiesis from yolk sac to fetal 
      liver. Reduced oxygenation is known to activate the hypoxia-inducible factor-1 
      (HIF-1), which in turn specifically induces expression of a variety of genes 
      among them erythropoietin (EPO). Although EBs increased EPO expression upon 
      hypoxic exposure, the altered beta-globin appearance was not related to EPO 
      levels as determined in EBs overexpressing EPO. Since mRNA from both mouse 
      HIF-1alpha isoforms was detected in all EBs tested at different differentiation 
      stages, we propose that HIF-1 modulates beta-globin expression during 
      development.
FAU - Bichet, S
AU  - Bichet S
AD  - Institute of Physiology, University of Zurich-Irchel, 8057 Zurich, Switzerland.
FAU - Wenger, R H
AU  - Wenger RH
FAU - Camenisch, G
AU  - Camenisch G
FAU - Rolfs, A
AU  - Rolfs A
FAU - Ehleben, W
AU  - Ehleben W
FAU - Porwol, T
AU  - Porwol T
FAU - Acker, H
AU  - Acker H
FAU - Fandrey, J
AU  - Fandrey J
FAU - Bauer, C
AU  - Bauer C
FAU - Gassmann, M
AU  - Gassmann M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
RN  - 9004-22-2 (Globins)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Aerobiosis
MH  - Anaerobiosis
MH  - Animals
MH  - DNA-Binding Proteins/genetics
MH  - Embryonic and Fetal Development/drug effects/*genetics
MH  - *Gene Expression Regulation, Developmental/drug effects
MH  - Globins/*genetics
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Mice
MH  - Nuclear Proteins/genetics
MH  - Oxygen/*metabolism/pharmacology
MH  - *Transcription Factors
EDAT- 1999/02/11 00:00
MHDA- 1999/02/11 00:01
CRDT- 1999/02/11 00:00
PHST- 1999/02/11 00:00 [pubmed]
PHST- 1999/02/11 00:01 [medline]
PHST- 1999/02/11 00:00 [entrez]
AID - 10.1096/fasebj.13.2.285 [doi]
PST - ppublish
SO  - FASEB J. 1999 Feb;13(2):285-95. doi: 10.1096/fasebj.13.2.285.