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Cell type of origin dictates the route to pluripotency

Cell type of origin dictates the route to pluripotency
Cell type of origin dictates the route to pluripotency

Our current understanding of induced pluripotent stem cell (iPSC) generation has almost entirely been shaped by studies performed on reprogramming fibroblasts. However, whether the resulting model universally applies to the reprogramming process of other cell types is still largely unknown. By characterizing and profiling the reprogramming pathways of fibroblasts, neutrophils, and keratinocytes, we unveil that key events of the process, including loss of original cell identity, mesenchymal to epithelial transition, the extent of developmental reversion, and reactivation of the pluripotency network, are to a large degree cell-type specific. Thus, we reveal limitations for the use of fibroblasts as a universal model for the study of the reprogramming process and provide crucial insights about iPSC generation from alternative cell sources.

Animals, Cellular Reprogramming/physiology, Early Growth Response Protein 1/metabolism, Fibroblasts/cytology, Flow Cytometry, Humans, Induced Pluripotent Stem Cells/cytology, Keratinocytes/cytology, Neutrophils/cytology, Octamer Transcription Factor-3/metabolism
2211-1247
2649-2660
Nefzger, Christian M
a7cb9192-20e8-4c16-8b95-819f48e44a78
Rossello, Fernando J
23da3426-c789-47f4-99a5-1edca6792422
Chen, Joseph
366c5516-4ae2-4431-b641-47fc1f3941ff
Liu, Xiaodong
8a273952-e4cf-4345-b45c-072ba5ba74c3
Knaupp, Anja S
63f824f9-e2ee-4547-a4b6-c662ca96dcf3
Firas, Jaber
701f9812-ab5f-4c87-af20-0b0b0466bd58
Paynter, Jacob M
75caec97-236e-4f02-9e21-09b6af56d1eb
Pflueger, Jahnvi
f4cfe097-8ed8-4669-952e-2591447c5fca
Buckberry, Sam
fe0c626c-699f-4858-9572-5b1af9b18814
Lim, Sue Mei
c00d3220-328d-4c33-9b5b-9d375c9d4b22
Williams, Brenda
dacb51a0-a74f-4334-9349-ecb67160753e
Alaei, Sara
8a83f7d6-e8b6-4c33-8bad-c300ab428b1f
Faye-Chauhan, Keshav
bae647ee-7352-425c-af0a-cf9c96b3387b
Petretto, Enrico
a8a7d254-ea06-4ab3-ba7e-b653349a29f4
Nilsson, Susan K
5dfc39e2-e81e-4c03-afb2-6caed41a9a58
Lister, Ryan
7044ae6b-cc46-4912-aa85-243f98f45cf7
Ramialison, Mirana
d3001fe9-c674-448b-a5ce-ad8a13e6e1bf
Powell, David R
e6d2619b-f9ff-48e4-ae19-0448f6ced99a
Rackham, Owen J L
8122eb1f-6e9f-4da5-90e1-ce108ccbbcbf
Polo, Jose M
f55d7039-bd9e-4e56-98e3-fdf3d118d4f3
Nefzger, Christian M
a7cb9192-20e8-4c16-8b95-819f48e44a78
Rossello, Fernando J
23da3426-c789-47f4-99a5-1edca6792422
Chen, Joseph
366c5516-4ae2-4431-b641-47fc1f3941ff
Liu, Xiaodong
8a273952-e4cf-4345-b45c-072ba5ba74c3
Knaupp, Anja S
63f824f9-e2ee-4547-a4b6-c662ca96dcf3
Firas, Jaber
701f9812-ab5f-4c87-af20-0b0b0466bd58
Paynter, Jacob M
75caec97-236e-4f02-9e21-09b6af56d1eb
Pflueger, Jahnvi
f4cfe097-8ed8-4669-952e-2591447c5fca
Buckberry, Sam
fe0c626c-699f-4858-9572-5b1af9b18814
Lim, Sue Mei
c00d3220-328d-4c33-9b5b-9d375c9d4b22
Williams, Brenda
dacb51a0-a74f-4334-9349-ecb67160753e
Alaei, Sara
8a83f7d6-e8b6-4c33-8bad-c300ab428b1f
Faye-Chauhan, Keshav
bae647ee-7352-425c-af0a-cf9c96b3387b
Petretto, Enrico
a8a7d254-ea06-4ab3-ba7e-b653349a29f4
Nilsson, Susan K
5dfc39e2-e81e-4c03-afb2-6caed41a9a58
Lister, Ryan
7044ae6b-cc46-4912-aa85-243f98f45cf7
Ramialison, Mirana
d3001fe9-c674-448b-a5ce-ad8a13e6e1bf
Powell, David R
e6d2619b-f9ff-48e4-ae19-0448f6ced99a
Rackham, Owen J L
8122eb1f-6e9f-4da5-90e1-ce108ccbbcbf
Polo, Jose M
f55d7039-bd9e-4e56-98e3-fdf3d118d4f3

Nefzger, Christian M, Rossello, Fernando J, Chen, Joseph, Liu, Xiaodong, Knaupp, Anja S, Firas, Jaber, Paynter, Jacob M, Pflueger, Jahnvi, Buckberry, Sam, Lim, Sue Mei, Williams, Brenda, Alaei, Sara, Faye-Chauhan, Keshav, Petretto, Enrico, Nilsson, Susan K, Lister, Ryan, Ramialison, Mirana, Powell, David R, Rackham, Owen J L and Polo, Jose M (2017) Cell type of origin dictates the route to pluripotency. Cell Reports, 21 (10), 2649-2660. (doi:10.1016/j.celrep.2017.11.029).

Record type: Article

Abstract

Our current understanding of induced pluripotent stem cell (iPSC) generation has almost entirely been shaped by studies performed on reprogramming fibroblasts. However, whether the resulting model universally applies to the reprogramming process of other cell types is still largely unknown. By characterizing and profiling the reprogramming pathways of fibroblasts, neutrophils, and keratinocytes, we unveil that key events of the process, including loss of original cell identity, mesenchymal to epithelial transition, the extent of developmental reversion, and reactivation of the pluripotency network, are to a large degree cell-type specific. Thus, we reveal limitations for the use of fibroblasts as a universal model for the study of the reprogramming process and provide crucial insights about iPSC generation from alternative cell sources.

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More information

Accepted/In Press date: 8 November 2017
Published date: 5 December 2017
Additional Information: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Keywords: Animals, Cellular Reprogramming/physiology, Early Growth Response Protein 1/metabolism, Fibroblasts/cytology, Flow Cytometry, Humans, Induced Pluripotent Stem Cells/cytology, Keratinocytes/cytology, Neutrophils/cytology, Octamer Transcription Factor-3/metabolism

Identifiers

Local EPrints ID: 447595
URI: http://eprints.soton.ac.uk/id/eprint/447595
ISSN: 2211-1247
PURE UUID: ebafb41c-1738-4ffc-ad56-b4fba604ac48
ORCID for Owen J L Rackham: ORCID iD orcid.org/0000-0002-4390-0872

Catalogue record

Date deposited: 16 Mar 2021 17:45
Last modified: 17 Mar 2024 04:03

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Contributors

Author: Christian M Nefzger
Author: Fernando J Rossello
Author: Joseph Chen
Author: Xiaodong Liu
Author: Anja S Knaupp
Author: Jaber Firas
Author: Jacob M Paynter
Author: Jahnvi Pflueger
Author: Sam Buckberry
Author: Sue Mei Lim
Author: Brenda Williams
Author: Sara Alaei
Author: Keshav Faye-Chauhan
Author: Enrico Petretto
Author: Susan K Nilsson
Author: Ryan Lister
Author: Mirana Ramialison
Author: David R Powell
Author: Jose M Polo

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