Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs

Emily E. Burke; Joshua G. Chenoweth; Joo Heon Shin; Leonardo Collado-Torres; Suel Kee Kim; Nicola Micali; Yanhong Wang; Carlo Colantuoni; Richard E. Straub; Daniel J. Hoeppner; Huei Ying Chen; Alana Sellers; Kamel Shibbani; Gregory R. Hamersky; Marcelo Diaz Bustamante; Ba Doi N. Phan; William S. Ulrich; Cristian Valencia; Amritha Jaishankar; Amanda J. Price; Anandita Rajpurohit; Stephen A. Semick; Roland W. Bürli; James C. Barrow; Daniel J. Hiler; Stephanie C. Page; Keri Martinowich; Thomas M. Hyde; Joel E. Kleinman; Karen F. Berman; Jose A. Apud; Alan J. Cross; Nicholas J. Brandon; Daniel R. Weinberger; Brady J. Maher; Ronald D.G. McKay; Andrew E. Jaffe

doi:10.1038/s41467-019-14266-z

Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs

Emily E. Burke, Joshua G. Chenoweth, Joo Heon Shin, Leonardo Collado-Torres, Suel Kee Kim, Nicola Micali, Yanhong Wang, Carlo Colantuoni, Richard E. Straub, Daniel J. Hoeppner, Huei Ying Chen, Alana Sellers, Kamel Shibbani, Gregory R. Hamersky, Marcelo Diaz Bustamante, Ba Doi N. Phan, William S. Ulrich, Cristian Valencia, Amritha Jaishankar, Amanda J. PriceAnandita Rajpurohit, Stephen A. Semick, Roland W. Bürli, James C. Barrow, Daniel J. Hiler, Stephanie C. Page, Keri Martinowich, Thomas M. Hyde, Joel E. Kleinman, Karen F. Berman, Jose A. Apud, Alan J. Cross, Nicholas J. Brandon, Daniel R. Weinberger, Brady J. Maher, Ronald D.G. McKay, Andrew E. Jaffe

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16 Scopus citations

Abstract

Human induced pluripotent stem cells (hiPSCs) are a powerful model of neural differentiation and maturation. We present a hiPSC transcriptomics resource on corticogenesis from 5 iPSC donor and 13 subclonal lines across 9 time points over 5 broad conditions: self-renewal, early neuronal differentiation, neural precursor cells (NPCs), assembled rosettes, and differentiated neuronal cells. We identify widespread changes in the expression of both individual features and global patterns of transcription. We next demonstrate that co-culturing human NPCs with rodent astrocytes results in mutually synergistic maturation, and that cell type-specific expression data can be extracted using only sequencing read alignments without cell sorting. We lastly adapt a previously generated RNA deconvolution approach to single-cell expression data to estimate the relative neuronal maturity of iPSC-derived neuronal cultures and human brain tissue. Using many public datasets, we demonstrate neuronal cultures are maturationally heterogeneous but contain subsets of neurons more mature than previously observed.

Original language	English (US)
Article number	462
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-14266-z
State	Published - Dec 1 2020

ASJC Scopus subject areas

General Physics and Astronomy
General Chemistry
General Biochemistry, Genetics and Molecular Biology

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Burke, E. E., Chenoweth, J. G., Shin, J. H., Collado-Torres, L., Kim, S. K., Micali, N., Wang, Y., Colantuoni, C., Straub, R. E., Hoeppner, D. J., Chen, H. Y., Sellers, A., Shibbani, K., Hamersky, G. R., Diaz Bustamante, M., Phan, B. D. N., Ulrich, W. S., Valencia, C., Jaishankar, A., ... Jaffe, A. E. (2020). Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs. Nature communications, 11(1), Article 462. https://doi.org/10.1038/s41467-019-14266-z

Burke, EE, Chenoweth, JG, Shin, JH, Collado-Torres, L, Kim, SK, Micali, N, Wang, Y, Colantuoni, C, Straub, RE, Hoeppner, DJ, Chen, HY, Sellers, A, Shibbani, K, Hamersky, GR, Diaz Bustamante, M, Phan, BDN, Ulrich, WS, Valencia, C, Jaishankar, A, Price, AJ, Rajpurohit, A, Semick, SA, Bürli, RW, Barrow, JC, Hiler, DJ, Page, SC, Martinowich, K, Hyde, TM, Kleinman, JE, Berman, KF, Apud, JA, Cross, AJ, Brandon, NJ, Weinberger, DR, Maher, BJ, McKay, RDG & Jaffe, AE 2020, 'Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs', Nature communications, vol. 11, no. 1, 462. https://doi.org/10.1038/s41467-019-14266-z

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title = "Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs",

abstract = "Human induced pluripotent stem cells (hiPSCs) are a powerful model of neural differentiation and maturation. We present a hiPSC transcriptomics resource on corticogenesis from 5 iPSC donor and 13 subclonal lines across 9 time points over 5 broad conditions: self-renewal, early neuronal differentiation, neural precursor cells (NPCs), assembled rosettes, and differentiated neuronal cells. We identify widespread changes in the expression of both individual features and global patterns of transcription. We next demonstrate that co-culturing human NPCs with rodent astrocytes results in mutually synergistic maturation, and that cell type-specific expression data can be extracted using only sequencing read alignments without cell sorting. We lastly adapt a previously generated RNA deconvolution approach to single-cell expression data to estimate the relative neuronal maturity of iPSC-derived neuronal cultures and human brain tissue. Using many public datasets, we demonstrate neuronal cultures are maturationally heterogeneous but contain subsets of neurons more mature than previously observed.",

author = "Burke, {Emily E.} and Chenoweth, {Joshua G.} and Shin, {Joo Heon} and Leonardo Collado-Torres and Kim, {Suel Kee} and Nicola Micali and Yanhong Wang and Carlo Colantuoni and Straub, {Richard E.} and Hoeppner, {Daniel J.} and Chen, {Huei Ying} and Alana Sellers and Kamel Shibbani and Hamersky, {Gregory R.} and {Diaz Bustamante}, Marcelo and Phan, {Ba Doi N.} and Ulrich, {William S.} and Cristian Valencia and Amritha Jaishankar and Price, {Amanda J.} and Anandita Rajpurohit and Semick, {Stephen A.} and B{\"u}rli, {Roland W.} and Barrow, {James C.} and Hiler, {Daniel J.} and Page, {Stephanie C.} and Keri Martinowich and Hyde, {Thomas M.} and Kleinman, {Joel E.} and Berman, {Karen F.} and Apud, {Jose A.} and Cross, {Alan J.} and Brandon, {Nicholas J.} and Weinberger, {Daniel R.} and Maher, {Brady J.} and McKay, {Ronald D.G.} and Jaffe, {Andrew E.}",

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AU - Chenoweth, Joshua G.

AU - Shin, Joo Heon

AU - Collado-Torres, Leonardo

AU - Kim, Suel Kee

AU - Micali, Nicola

AU - Wang, Yanhong

AU - Colantuoni, Carlo

AU - Straub, Richard E.

AU - Hoeppner, Daniel J.

AU - Chen, Huei Ying

AU - Sellers, Alana

AU - Shibbani, Kamel

AU - Hamersky, Gregory R.

AU - Diaz Bustamante, Marcelo

AU - Phan, Ba Doi N.

AU - Ulrich, William S.

AU - Valencia, Cristian

AU - Jaishankar, Amritha

AU - Price, Amanda J.

AU - Rajpurohit, Anandita

AU - Semick, Stephen A.

AU - Bürli, Roland W.

AU - Barrow, James C.

AU - Hiler, Daniel J.

AU - Page, Stephanie C.

AU - Martinowich, Keri

AU - Hyde, Thomas M.

AU - Kleinman, Joel E.

AU - Berman, Karen F.

AU - Apud, Jose A.

AU - Cross, Alan J.

AU - Brandon, Nicholas J.

AU - Weinberger, Daniel R.

AU - Maher, Brady J.

AU - McKay, Ronald D.G.

AU - Jaffe, Andrew E.

PY - 2020/12/1

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Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs

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