The homeobox gene Hhex regulates the earliest stages of definitive hematopoiesis

A crucial role for the homeodomain transcription factor Hhex in lymphopoiesis

“…Our findings are reminiscent of studies of Hhex 2/2 embryoid body differentiation, which have shown loss of cyclin D1 expression in Hhex 2/2 definitive hematopoietic progenitors and a block in the cell cycle at the G2/M transition. 19 Together, these findings suggest that Hhex regulates embryonic hematopoiesis and lymphoid development via similar mechanisms. As Hhex is thought to operate primarily as a transcriptional repressor, it is unlikely to activate Ccnd1 directly.…”

“…[17][18][19] In contrast, primitive hematopoiesis was unaffected, implying a specific requirement for Hhex in the specification of definitive HSCs. Moreover, in blastocyst chimera experiments, contribution of Hhex 2/2 cells to hematopoietic tissues was severely reduced, indicating a defect in contribution to definitive hematopoiesis during embryogenesis in vivo.…”

“…Using blastocyst compensation of Rag1 2/2 mice, it has been shown that Hhex is required for B-cell development and function, 16 whereas, in embryonic stem cell differentiation models, Hhex is required for maturation and proliferation of definitive HSCs. [17][18][19] Thus, Hhex is postulated to play a role in hematopoietic differentiation and stem cell self-renewal in the adult. To address this, we have obtained mice conditionally targeted for Hhex and used these to delete Hhex in the hematopoietic system of adult mice.…”

Differentiated human stem cells resemble fetal, not adult, β cells

“…The differentially expressed genes presented in this study could be used as genetic markers of human β-cell maturation. Down-regulation or up-regulation of several genes such as NFIB, prospero homeobox 1 (PROX1), HHEX, and KLF9 has been implicated in the maturation of other cellular lineages, suggesting that these may be transcription factors involved in the pan-tissue transitions from fetal to adult transcriptional programs (39)(40)(41)(42).…”

Endodermal and mesenchymal cross talk: a crossroad for the maturation of foregut organs

“…In the liver, Hhex is expressed in both endodermal and ECs but not in STM or definitive erythroids (43). Hhex has no effect on the development of primitive erythroids, but the absence of Hhex leads to a failure of definitive erythropoiesis both in vitro (44) and in vivo (23) (unpublished data). A role for Hhex in foregut organ development has also been observed in Zebrafish (45) and Xenopus (46).…”