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. Nefzger et al. find that the molecular reprogramming trajectories of fibroblasts, neutrophils, and keratinocytes have a cell-type-specific component that only fully converges in induced pluripotent stem cells. The authors also identify universal changes shared by all three cell types, including two transcriptional waves and a conserved transcriptional program involving Egr1 downregulation.
| Language | English |
|---|---|
| Pages | 2649-2660 |
| Number of pages | 12 |
| Journal | Cell Reports |
| Volume | 21 |
| Issue number | 10 |
| DOIs | |
| State | Published - 5 Dec 2017 |
Keywords
- Egr1
- fibroblasts
- induced pluripotent stem cells
- keratinocytes
- neutrophils
- reprogramming
- transcriptional dynamics
Cite this
}
Cell Type of Origin Dictates the Route to Pluripotency. / 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.; Polo, Jose M.
In: Cell Reports, Vol. 21, No. 10, 05.12.2017, p. 2649-2660.Research output: Research - peer-review › Article
TY - JOUR
T1 - Cell Type of Origin Dictates the Route to Pluripotency
AU - Nefzger,Christian M.
AU - Rossello,Fernando J.
AU - Chen,Joseph
AU - Liu,Xiaodong
AU - Knaupp,Anja S.
AU - Firas,Jaber
AU - Paynter,Jacob M.
AU - Pflueger,Jahnvi
AU - Buckberry,Sam
AU - Lim,Sue Mei
AU - Williams,Brenda
AU - Alaei,Sara
AU - Faye-Chauhan,Keshav
AU - Petretto,Enrico
AU - Nilsson,Susan K.
AU - Lister,Ryan
AU - Ramialison,Mirana
AU - Powell,David R.
AU - Rackham,Owen J.L.
AU - Polo,Jose M.
PY - 2017/12/5
Y1 - 2017/12/5
N2 - 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. Nefzger et al. find that the molecular reprogramming trajectories of fibroblasts, neutrophils, and keratinocytes have a cell-type-specific component that only fully converges in induced pluripotent stem cells. The authors also identify universal changes shared by all three cell types, including two transcriptional waves and a conserved transcriptional program involving Egr1 downregulation.
AB - 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. Nefzger et al. find that the molecular reprogramming trajectories of fibroblasts, neutrophils, and keratinocytes have a cell-type-specific component that only fully converges in induced pluripotent stem cells. The authors also identify universal changes shared by all three cell types, including two transcriptional waves and a conserved transcriptional program involving Egr1 downregulation.
KW - Egr1
KW - fibroblasts
KW - induced pluripotent stem cells
KW - keratinocytes
KW - neutrophils
KW - reprogramming
KW - transcriptional dynamics
UR - http://www.scopus.com/inward/record.url?scp=85037615560&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2017.11.029
DO - 10.1016/j.celrep.2017.11.029
M3 - Article
VL - 21
SP - 2649
EP - 2660
JO - Cell Reports
T2 - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 10
ER -