Molecular Signatures of Tissue-Specific Microvascular Endothelial Cell Heterogeneity in Organ Maintenance and Regeneration

Daniel J. Nolan, Michael Ginsberg, Edo Israely, Brisa Palikuqi, Michael G. Poulos, Daylon James, Bi Sen Ding, William Schachterle, Ying Liu, Zev Rosenwaks, Jason M. Butler, Jenny Xiang, Arash Rafii, Koji Shido, Sina Y. Rabbany, Olivier Elemento, Shahin Rafii

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269 Citations (Scopus)

Abstract

Microvascular endothelial cells (ECs) within different tissues are endowed with distinct but as yet unrecognized structural, phenotypic, and functional attributes. We devised EC purification, cultivation, profiling, and transplantation models that establish tissue-specific molecular libraries of ECs devoid of lymphatic ECs or parenchymal cells. These libraries identify attributes that confer ECs with their organotypic features. We show that clusters of transcription factors, angiocrine growth factors, adhesion molecules, and chemokines are expressed in unique combinations by ECs of each organ. Furthermore, ECs respond distinctly in tissue regeneration models, hepatectomy, and myeloablation. To test the data set, we developed a transplantation model that employs generic ECs differentiated from embryonic stem cells. Transplanted generic ECs engraft into regenerating tissues and acquire features of organotypic ECs. Collectively, we demonstrate the utility of informational databases of ECs toward uncovering the extravascular and intrinsic signals that define EC heterogeneity. These factors could be exploited therapeutically to engineer tissue-specific ECs for regeneration.

Original languageEnglish
Pages (from-to)204-219
Number of pages16
JournalDevelopmental Cell
Volume26
Issue number2
DOIs
Publication statusPublished - 29 Jul 2013

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ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Cite this

Nolan, D. J., Ginsberg, M., Israely, E., Palikuqi, B., Poulos, M. G., James, D., Ding, B. S., Schachterle, W., Liu, Y., Rosenwaks, Z., Butler, J. M., Xiang, J., Rafii, A., Shido, K., Rabbany, S. Y., Elemento, O., & Rafii, S. (2013). Molecular Signatures of Tissue-Specific Microvascular Endothelial Cell Heterogeneity in Organ Maintenance and Regeneration. Developmental Cell, 26(2), 204-219. https://doi.org/10.1016/j.devcel.2013.06.017