title: SOX7-enforced expression promotes the expansion of adult blood progenitors and blocks B-cell development.
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.
authors.affiliation: Stem Cell Hematopoiesis Group, Cancer Research UK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Cuvertino
authors.affiliation: Stem Cell Biology Group, Cancer Research UK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK georges.lacaud@cruk.manchester.ac.uk.
authors.forename: Georges
authors.initials: G
authors.lastname: Lacaud
authors.affiliation: Stem Cell Hematopoiesis Group, Cancer Research UK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK valerie.kouskoff@cruk.manchester.ac.uk.
authors.forename: Valerie
authors.initials: V
authors.lastname: Kouskoff
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D000066673:Cell Self Renewal; D018920:Coculture Techniques; D005260:Female; D006410:Hematopoiesis; D006706:Homeostasis; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D055760:SOXF Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D055760:SOXF Transcription Factors; C102515:Sox7 protein, mouse
keywords: SOX7; haematopoiesis; transcription factor