A population of hematopoietic stem cells derives from GATA4-expressing progenitors located in the placenta and lateral mesoderm of mice

Cañete, A., Carmona, R., Ariza, L., Sánchez, M. J., Rojas, A. and Muñoz-Chápuli, R. (2017) A population of hematopoietic stem cells derives from GATA4-expressing progenitors located in the placenta and lateral mesoderm of mice. Haematologica, 102(4), pp. 647-655. (doi: 10.3324/haematol.2016.155812) (PMID:28057738) (PMCID:PMC5395105)

Abstract

GATA transcription factors are expressed in the mesoderm and endoderm during development. GATA1–3, but not GATA4, are critically involved in hematopoiesis. An enhancer (G2) of the mouse Gata4 gene directs its expression throughout the lateral mesoderm and the allantois, beginning at embryonic day 7.5, becoming restricted to the septum transversum by embryonic day 10.5, and disappearing by midgestation. We have studied the developmental fate of the G2-Gata4 cell lineage using a G2-Gata4Cre;R26REYFP mouse line. We found a substantial number of YFP+ hematopoietic cells of lymphoid, myeloid and erythroid lineages in embryos. Fetal CD41+/cKit+/CD34+ and Lin−/cKit+/CD31+ YFP+ hematopoietic progenitors were much more abundant in the placenta than in the aorta-gonad-mesonephros area. They were clonogenic in the MethoCult assay and fully reconstituted hematopoiesis in myeloablated mice. YFP+ cells represented about 20% of the hematopoietic system of adult mice. Adult YFP+ hematopoietic stem cells constituted a long-term repopulating, transplantable population. Thus, a lineage of adult hematopoietic stem cells is characterized by the expression of GATA4 in their embryonic progenitors and probably by its extraembryonic (placental) origin, although GATA4 appeared not to be required for hematopoietic stem cell differentiation. Both lineages basically showed similar physiological behavior in normal mice, but clinically relevant properties of this particular hematopoietic stem cell population should be checked in physiopathological conditions.

• Item Type: Articles
• Additional Information: This study was supported (in part) by research funding from grants BFU2014-52299-P (The Spanish Ministry of Economy), RD12/0019-0022 (Instituto de Salud Carlos III-TERCEL net-work), and P11-CTS-07564 (Junta de Andalucía) to RM-C and PI14-00804 (Instituto de Salud Carlos III cofounded by FEDER funding) to AR.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Canete Sanchez, Mrs Ana Elodia
• Authors: Cañete, A., Carmona, R., Ariza, L., Sánchez, M. J., Rojas, A., and Muñoz-Chápuli, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Haematologica
• Publisher: Ferrata Storti Foundation
• ISSN: 0390-6078
• ISSN (Online): 1592-8721
• Published Online: 05 January 2017
• Copyright Holders: Copyright © 2017 Ferrata Storti Foundation
• First Published: First published in Haematologica 102(4):647-655
• Publisher Policy: Reproduced under a Creative Commons License