@article{10902/34980,
year = {2021},
url = {https://hdl.handle.net/10902/34980},
abstract = {At early developmental stages, limb bud mesodermal undifferentiated cells are morphologically indistinguishable. Although the identification of several mesodermal skeletal progenitor cell populations has been recognized, in advanced stages of limb development here we identified and characterized the differentiation hierarchy of two new early limb bud subpopulations of skeletal progenitors defined by the differential expression of the SCA-1 marker. Based on tissue localization of the mesenchymal stromal cell-associated markers (MSC-am) CD29, Sca-1, CD44, CD105, CD90, and CD73, we identified, by multiparametric analysis, the presence of cell subpopulations in the limb bud capable of responding to inductive signals differentially, namely, sSca+ and sSca- cells. In concordance with its gene expression profile, cell cultures of the sSca+ subpopulation showed higher osteogenic but lower chondrogenic capacity than those of sSca-. Interestingly, under high-density conditions, fibroblast-like cells in the sSca+ subpopulation were abundant. Gain-of-function employing micromass cultures and the recombinant limb assay showed that SCA-1 expression promoted tenogenic differentiation, whereas chondrogenesis is delayed. This model represents a system to determine cell differentiation and morphogenesis of different cell subpopulations in similar conditions like in vivo. Our results suggest that the limb bud is composed of a heterogeneous population of progenitors that respond differently to local differentiation inductive signals in the early stages of development, where SCA-1 expression may play a permissive role during cell fate.},
organization = {Funding: This work was supported by the Dirección General de Asuntos del Personal Académico (DGAPA)-Universidad Nacional Autónoma de México (grant numbers IN211117 and IN213314) and Consejo Nacional de Ciencia y Tecnología (CONACyT) (grant number 1887 CONACyT-Fronteras de la Ciencia) awarded to JC-M. This work was supported by a grant (BFU2017-84046-P) from the Spanish Science and Innovation Ministry awarded to JH. JM-L was the recipient of a postdoctoral fellowship from the Consejo Nacional de Ciencia y Tecnología (CONACyT-Fronteras de la Ciencia-1887). Acknowledgments: We extend thanks to Miguel Tapia-Rodríguez from the Unidad de Microscopía, M. en C. Carlos Castellanos Barba from Laboratorio Nacional de Citometría de Flujo (LabNalCit-CONACyT), members from Laboratorio Nacional de Recursos Genómicos (LaNRenGen-CONACyT), MVZ Georgina Díaz Herrera and members from Unidad de Modelos Biológicos, and to Lic. Lucía Brito Ocampo, all from the Instituto de Investigaciones Biomédicas, UNAM, for their technical assistance. We also thank Argelia Sarahí García-Cervera for the flow cytometry analysis in E11.5 and E12.5 and Maria Valeria Chimal-Montes de Oca for artwork. We also thank Sonia Perez-Mantecon, Montse Fernandez-Calderón, and Susana Dawalibi from the Departamento de Anatomía of Facultad de Medicina, Universidad de Cantabria in Spain for all their technical assistance.},
publisher = {Frontiers},
publisher = {Frontiers in Cell and Developmental Biology, 2021, 9, 656999},
title = {SCA-1/Ly6A mesodermal skeletal progenitor subpopulations reveal differential commitment of early limb bud cells},
author = {Marín-Llera, Jessica Cristina and Lorda Diez, Carlos Ignacio and Hurlé González, Juan M. and Chimal-Monroy, Jesús},
}