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Cited by 489

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Mapping the Pairwise Choices Leading from Pluripotency to Human Bone, Heart, and Other Mesoderm Cell Types

Open access
Loh, Kyle M., Chen, Angela, Koh, Pang Wei, Deng, Tianda Z., Sinha, Rahul, Tsai, Jonathan M., Barkal, Amira A., Shen, Kimberle Y., Jain, Rajan, Morganti, Rachel M., Shyh-Chang, Ng, Fernhoff, Nathaniel B., George, Benson M., Wernig, Gerlinde, Salomon, Rachel E.A., Chen, Zhenghao, Vogel, Hannes, Epstein, Jonathan A., Kundaje, Anshul, Talbot, William S., Beachy, Philip A., Ang, Lay Teng, Weissman, Irving L.·2016·Cell

Abstract

SUMMARY Stem-cell differentiation to desired lineages requires navigating alternating developmental paths often leading to unwanted cell-types. Hence comprehensive developmental roadmaps are crucial to channel stem-cell differentiation towards desired fates. To this end, here we map bifurcating lineage choices leading from pluripotency to twelve human mesodermal lineages, including bone, muscle and heart. We defined the extrinsic signals controlling each binary lineage decision, enabling us to logically block differentiation towards unwanted fates and rapidly steer pluripotent stem cells towards 80–99% pure human mesodermal lineages at most branchpoints. This strategy enabled the generation of human bone and heart progenitors that could engraft in respective in vivo models. Mapping stepwise chromatin and single-cell gene expression changes in mesoderm development uncovered somite segmentation, a previously-unobservable human embryonic event transiently marked by HOPX expression. Collectively this roadmap enables navigation of mesodermal development to produce transplantable human tissue progenitors and uncover developmental processes.

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Crossref · 10.1016/j.cell.2016.06.011

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Authors
Loh, K. M., Chen, A., Koh, P. W., Deng, T. Z., Sinha, R., Tsai, J. M., Barkal, A. A., Shen, K. Y., Jain, R., Morganti, R. M., Shyh-Chang, N., Fernhoff, N. B., George, B. M., Wernig, G., Salomon, R. E. A., Chen, Z., Vogel, H., Epstein, J. A., Kundaje, A., Talbot, W. S., Beachy, P. A., Ang, L. T., & Weissman, I. L.
Venue
Cell
Publisher
Elsevier BV
Published
2016-07
Volume
166
Issue
2
Pages
451-467
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2461230718
Cited by
489
References
4
FWCI
18.21
Type
journal article
Language
en
Open access
bronze

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