Gata1 expression driven by the alternative HS2 enhancer in the spleen rescues the hematopoietic failure induced by the hypomorphic Gata1low mutation.
Rigorously defined reconstitution assays developed in recent years have allowed recognition of the delicate relationship that exists between hematopoietic stem cells and their niches. This balance ensures that hematopoiesis occurs in the marrow under steady-state conditions. However, during development, recovery from hematopoietic stress and in myeloproliferative disorders, hematopoiesis occurs in extramedullary sites whose microenvironments are still poorly defined. The hypomorphic Gata1(low) mutation deletes the regulatory sequences of the gene necessary for its expression in hematopoietic cells generated in the marrow. By analyzing the mechanism that rescues hematopoiesis in mice carrying this mutation, we provide evidence that extramedullary microenvironments sustain maturation of stem cells that would be otherwise incapable of maturing in the marrow.
Migliaccio
Anna Rita
AR
Department of Hematology/Oncology and Molecular Medicine, Instituto Superiore Sanità, Rome, Italy. annarita.migliaccio@mssm.edu
Martelli
Fabrizio
F
Verrucci
Maria
M
Sanchez
Massimo
M
Valeri
Mauro
M
Migliaccio
Giovanni
G
Vannucchi
Alessandro Maria
AM
Zingariello
Maria
M
Di Baldassarre
Angela
A
Ghinassi
Barbara
B
Rana
Rosa Alba
RA
van Hensbergen
Yvette
Y
Fibbe
Willem E
WE
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006411:Hematopoiesis, Extramedullary; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013312:Stress, Physiological / Q000235:genetics
D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse