Participation in haematopoiesis RUNX1

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runx1 plays crucial role in adult (definitive) haematopoiesis during embryonic development. expressed in haematopoietic sites contribute formation of haematopoietic stem , progenitor cells (hspcs), including yolk sac, allantois, placenta, para-aortic splanchnopleura (p-sp; (the visceral mesodermal layer), aorta-gonad-mesonephros (agm) , umbilical , vitelline arteries. hspcs generated via hemogenic endothelium, special subset of endothelial cells scattered within blood vessels can differentiate haematopoietic cells. emergence of hspcs studied in mouse , zebrafish animal models, in hspcs appear “intra-aortic” clusters adhere ventral wall of dorsal aorta. runx1 or cbf takes part in process mediating transition of endothelial cell become haematopoietic cell. interestingly, there increasing evidence runx1 may important during primitive haematopoiesis. because in runx1 knockout mice, primitive erythrocytes displayed defective morphology , size of blast cell population substantially reduced, apart absence of hspcs result in embryonic lethality embryonic day (e) 11.5 – 12.5.


at molecular level, expression of gene runx1 upregulated runx1 intronic cis-regulatory element (+23 runx1 enhancer). +23 runx1 enhancer contains conserved motifs encourage binding of various haematopoiesis related regulators such gata2, ets factors (fli-1, elf-1, pu.1) , scl / lmo2 / ldb1 complex, runx1 acting in auto-regulatory loop. mentioned before, main role of runx1 modulate fate of haematopoietic cells. can achieved binding thrombopoietin (tpo) recaptor/ c-mpl promoter, followed recruitment of transcription activators or repressors in order promote transition of hemogenic endothelium hscs, or differentiation linages of lower haematopoetic hierarchies. runx1 can modulate own level upregulating expression of smad6 target proteolysis.








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