Találati lista | Tudóstér

001-es BibID:	BIBFORM019005
Első szerző:	Iacovino, Michelina
Cím:	HoxA3 is an apical regulator of haemogenic endothelium / Iacovino Michelina, Chong Diana, Szatmari Istvan, Hartweck Lynn, Rux Danielle, Caprioli Arianna, Cleaver Ondine, Kyba Michael
Dátum:	2011
ISSN:	1465-7392
Megjegyzések:	During development, haemogenesis occurs invariably at sites of vasculogenesis. Between embryonic day (E) 9.5 and E10.5 in mice, endothelial cells in the caudal part of the dorsal aorta generate haematopoietic stem cells and are referred to as haemogenic endothelium. The mechanisms by which haematopoiesis is restricted to this domain, and how the morphological transformation from endothelial to haematopoietic is controlled are unknown. We show here that HoxA3, a gene uniquely expressed in the embryonic but not yolk sac vasculature, restrains haematopoietic differentiation of the earliest endothelial progenitors, and induces reversion of the earliest haematopoietic progenitors into CD41-negative endothelial cells. This reversible modulation of endothelial-haematopoietic state is accomplished by targeting key haematopoietic transcription factors for downregulation, including Runx1, Gata1, Gfi1B, Ikaros, and PU.1. Through loss-of-function, and gain-of-function epistasis experiments, and the identification of antipodally regulated targets, we show that among these factors, Runx1 is uniquely able to erase the endothelial program set up by HoxA3. These results suggest both why a frank endothelium does not precede haematopoiesis in the yolk sac, and why haematopoietic stem cell generation requires Runx1 expression only in endothelial cells.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok levél
Megjelenés:	Nature Cell Biology. - 13 : 1 (2011), p. 72-78. -
További szerzők:	Chong, Diana Szatmári István (1971-) (biológus) Hartweck, Lynn Rux, Danielle Caprioli, Arianna Cleaver, Ondine Kyba, Michael
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:

001-es BibID:	BIBFORM019228
Első szerző:	Szatmári István (biológus)
Cím:	The Retinoid Signaling Pathway Inhibits Hematopoiesis and Uncouples from the Hox Genes During Hematopoietic Development / Szatmari Istvan, Iacovino Michelina, Kyba Michael
Dátum:	2010
ISSN:	1066-5099
Megjegyzések:	Retinoic acid (RA) is a well-established inducer of Hox genes during development of neurectoderm, however effects of RA on Hox expression are poorly defined in mesoderm and not defined in the hematopoietic compartment. Both Hox genes and retinoid signaling have been suggested to modulate hematopoietic stem cell (HSC) self-renewal, supporting the notion that RA signaling might drive HSC self-renewal through Hox gene induction. Here, we investigate this possibility by comprehensively evaluating Hox gene expression using mouse embryonic stem cells differentiated in vitro. In unspecified mesoderm, we find that RA coordinately upregulates anterior 3' Hox genes from clusters A, B, and C, and downregulates posterior 5' Hox genes from clusters A-D. However, hematopoietic development of mesoderm was inhibited by RA, and we find further that retinoids are entirely dispensable for hematopoiesis in vitro. More surprisingly, in fully specified hematopoietic progenitors, Hox genes are refractory to regulation by RA, although other RA targets are normally regulated. Pulses of RA exposure demonstrate that the Hox complexes are decoupled from RA regulation progressively in lateral plate mesoderm as it undergoes hematopoietic specification. Thus, Hox genes are targets of the RA pathway only in selected cell types, and are clearly not regulated by RA in the earliest hematopoietic progenitors. We propose that the developmental uncoupling of the Hox complexes protects the Hox code from potential RA signaling centers as HSCs migrate or circulate during development.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Stem Cells. - 28 : 9 (2010), p. 1518-1529. -
További szerzők:	Iacovino, Michelina Kyba, Michael
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon: