Page 175 - 2019_09-HaematologicaMondo-web

Platelet Biology & its Disorders
CD45 expression discriminates waves of embryonic megakaryocytes in the mouse
Ferrata Storti Foundation
Haematologica 2019 Volume 104(9):1853-1865
Isabel Cortegano,1 Natalia Serrano,2 Carolina Ruiz,1 Mercedes Rodríguez,1 Carmen Prado,1 Mario Alía,1 Andrés Hidalgo,3 Eva Cano,4 Belén de Andrés1 and María-Luisa Gaspar1
1Department of Immunology, Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Majadahonda; 2Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CBMSO-CSIC), Madrid; 3Area of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares, Madrid and 4Neuroinflamation Unit, Chronic Diseases Research Program, Instituto de Salud Carlos III (ISCIII), Majadahonda, Spain
ABSTRACT
Embryonic megakaryopoiesis starts in the yolk sac on gestational day 7.5 as part of the primitive wave of hematopoiesis, and it continues in the fetal liver when this organ is colonized by hematopoietic progeni- tors between day 9.5 and 10.5, as the definitive hematopoiesis wave. We characterized the precise phenotype of embryo megakaryocytes in the liver at gestational day 11.5, identifying them as CD41++CD45- CD9++CD61+MPL+CD42c+ tetraploid cells that express megakaryocyte-spe- cific transcripts and display differential traits when compared to those pres- ent in the yolk sac at the same age. In contrast to megakaryocytes from adult bone marrow, embryo megakaryocytes are CD45- until day 13.5 of gesta- tion, as are both the megakaryocyte progenitors and megakaryocyte/ery- throid-committed progenitors. At gestational day 11.5, liver and yolk sac also contain CD41+CD45+ and CD41+CD45- cells. These populations, and that of CD41++CD45-CD42c+ cells, isolated from liver, differentiate in culture into CD41++CD45-CD42c+ proplatelet-bearing megakaryocytes. Also present at this time are CD41-CD45++CD11b+ cells, which produce low numbers of CD41++CD45-CD42c+ megakaryocytes in vitro, as do fetal liver cells express- ing the macrophage-specific Csf receptor-1 (Csf1r/CD115) from MaFIA transgenic mice, which give rise poorly to CD41++CD45-CD42c+ embryo megakaryocytes both in vivo and in vitro. In contrast, around 30% of adult megakaryocytes (CD41++CD45++CD9++CD42c+) from C57BL/6 and MaFIA mice express CD115. We propose that differential pathways operating in the mouse embryo liver at gestational day 11.5 beget CD41++CD45-CD42c+ embryo megakaryocytes that can be produced from CD41+CD45- or from CD41+CD45+ cells, at difference from those from bone marrow.
Introduction
Megakaryocytes are the hematopoietic cells responsible for the production of platelets. In adults, these cells are generated in the bone marrow (BM) from hematopoietic stem cells (HSC) via a common megakaryocyte and erythroid progen- itor (MEP) that expresses the receptor for SCF (c-Kit) and is negative for lineage-spe- cific antigens (Lin-), for the stem cell antigen-1 (Sca1), and for the fms-related tyrosine kinase 3 receptor, Flt3/CD135 (Flt3-LS-K cells).1 Nevertheless differentiation into all hematopoietic lineages, including the megakaryocyte/erythroid, from Flt3+ progeni- tors was also obtained.2 The hierarchical model of hematopoiesis defines progres- sively restricted lineage-committed progenitors. From HSC a pool of multipotent pro- genitors (MPP) produces common lymphoid progenitors (CLP) and common myeloid progenitors (CMP), these latter giving rise to MEP and granulocyte/macrophage pro- genitors (GMP).3,4 However, several recent reports suggest that megakaryocyte/ery- throid-commitment may happen directly from HSC or from MPP, supporting a model of multiple lineage commitments occurring in parallel within the HSC/MPP cell pool.5-8 Among CMP, CD41+ cells that express a megakaryocyte-specific signa-
Correspondence:
ISABEL CORTEGANO
icortegano@isciii.es
MARÍA-LUISA GASPAR mlgaspar@isciii.es
Received: March 8, 2018. Accepted: December 14, 2018. Pre-published: December 20, 2018.
doi:10.3324/haematol.2018.192559
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/9/1853
©2019 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
haematologica | 2019; 104(9)
1853
ARTICLE