Abstract
During embryogenesis, the three SOXF transcription factors, SOX7, SOX17 and SOX18, regulate the specification of the cardiovascular system and are also involved in the development of haematopoiesis. The ectopic expression of SOX17 in both embryonic and adult blood cells enhances self-renewal. Likewise, the enforced expression of SOX7 during embryonic development promotes the proliferation of early blood progenitors and blocks lineage commitment. However, whether SOX7 expression can also affect the self-renewal of adult blood progenitors has never been explored. In this study, we demonstrate using an inducible transgenic mouse model that the enforced expression of Sox7 ex vivo in bone marrow/stroma cell co-culture promotes the proliferation of blood progenitors which retain multi-lineage short-term engrafting capacity. Furthermore, SOX7 expression induces a profound block in the generation of B lymphocytes. Correspondingly, the ectopic expression of SOX7 in vivo results in dramatic alterations of the haematopoietic system, inducing the proliferation of blood progenitors in the bone marrow while blocking B lymphopoiesis. In addition, SOX7 expression induces extra-medullary haematopoiesis in the spleen and liver. Together, these data demonstrate that the uncontrolled expression of the transcription factor SOX7 in adult haematopoietic cells has dramatic consequences on blood homeostasis.
Highlights
The SOX family of transcription factors is highly conserved throughout evolution and in mouse comprises 20 members divided into subgroups based on sequence similarities [1]
To determine whether SOX7-enforced expression in adult blood cells confers a proliferative advantage as observed during embryonic development, we investigated the consequences of Sox7-enforced expression on haematopoiesis
When Sox7 expression was induced during the co-culture, the frequency of MAC1þ myeloid cells remained high upon successive passages with the progressive appearance of a MAC1low population expressing SOX7::GFP at high level
Summary
The SOX family of transcription factors is highly conserved throughout evolution and in mouse comprises 20 members divided into subgroups based on sequence similarities [1]. SOX factors are essential for the regulation of many developmental processes, often implicating several SOX factors in one developmental path, such as, for example, SRY and SOX9 in sex determination or SOX1, 2 and 3 in neural tube formation [2]. In addition to their critical roles during embryogenesis, SOX factors are often implicated in the maintenance and identity of stem cell populations [3]. At E10.5 of embryonic development, the three SOXF factors are found expressed in the endothelium lining of the dorsal aorta and in the emerging clusters of haematopoietic cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
