Production of human entorhinal stellate cell-like cells by forward programming shows an important role of Foxp1 in reprogramming

Research output: Contribution to journalJournal articlepeer-review

Standard

Production of human entorhinal stellate cell-like cells by forward programming shows an important role of Foxp1 in reprogramming. / Bergmann, Tobias; Liu, Yong; Skov, Jonathan; Mogus, Leo; Lee, Julie; Pfisterer, Ulrich; Handfield, Louis Francois; Asenjo-Martinez, Andrea; Lisa-Vargas, Irene; Seemann, Stefan E.; Lee, Jimmy Tsz Hang; Patikas, Nikolaos; Kornum, Birgitte Rahbek; Denham, Mark; Hyttel, Poul; Witter, Menno P.; Gorodkin, Jan; Pers, Tune H.; Hemberg, Martin; Khodosevich, Konstantin; Hall, Vanessa Jane.

In: Frontiers in Cell and Developmental Biology, Vol. 10, 976549, 2022.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Bergmann, T, Liu, Y, Skov, J, Mogus, L, Lee, J, Pfisterer, U, Handfield, LF, Asenjo-Martinez, A, Lisa-Vargas, I, Seemann, SE, Lee, JTH, Patikas, N, Kornum, BR, Denham, M, Hyttel, P, Witter, MP, Gorodkin, J, Pers, TH, Hemberg, M, Khodosevich, K & Hall, VJ 2022, 'Production of human entorhinal stellate cell-like cells by forward programming shows an important role of Foxp1 in reprogramming', Frontiers in Cell and Developmental Biology, vol. 10, 976549. https://doi.org/10.3389/fcell.2022.976549

APA

Bergmann, T., Liu, Y., Skov, J., Mogus, L., Lee, J., Pfisterer, U., Handfield, L. F., Asenjo-Martinez, A., Lisa-Vargas, I., Seemann, S. E., Lee, J. T. H., Patikas, N., Kornum, B. R., Denham, M., Hyttel, P., Witter, M. P., Gorodkin, J., Pers, T. H., Hemberg, M., ... Hall, V. J. (2022). Production of human entorhinal stellate cell-like cells by forward programming shows an important role of Foxp1 in reprogramming. Frontiers in Cell and Developmental Biology, 10, [976549]. https://doi.org/10.3389/fcell.2022.976549

Vancouver

Bergmann T, Liu Y, Skov J, Mogus L, Lee J, Pfisterer U et al. Production of human entorhinal stellate cell-like cells by forward programming shows an important role of Foxp1 in reprogramming. Frontiers in Cell and Developmental Biology. 2022;10. 976549. https://doi.org/10.3389/fcell.2022.976549

Author

Bergmann, Tobias ; Liu, Yong ; Skov, Jonathan ; Mogus, Leo ; Lee, Julie ; Pfisterer, Ulrich ; Handfield, Louis Francois ; Asenjo-Martinez, Andrea ; Lisa-Vargas, Irene ; Seemann, Stefan E. ; Lee, Jimmy Tsz Hang ; Patikas, Nikolaos ; Kornum, Birgitte Rahbek ; Denham, Mark ; Hyttel, Poul ; Witter, Menno P. ; Gorodkin, Jan ; Pers, Tune H. ; Hemberg, Martin ; Khodosevich, Konstantin ; Hall, Vanessa Jane. / Production of human entorhinal stellate cell-like cells by forward programming shows an important role of Foxp1 in reprogramming. In: Frontiers in Cell and Developmental Biology. 2022 ; Vol. 10.

Bibtex

@article{028c241d080a49a494590eb724bf93f8,
title = "Production of human entorhinal stellate cell-like cells by forward programming shows an important role of Foxp1 in reprogramming",
abstract = "Stellate cells are principal neurons in the entorhinal cortex that contribute to spatial processing. They also play a role in the context of Alzheimer{\textquoteright}s disease as they accumulate Amyloid beta early in the disease. Producing human stellate cells from pluripotent stem cells would allow researchers to study early mechanisms of Alzheimer{\textquoteright}s disease, however, no protocols currently exist for producing such cells. In order to develop novel stem cell protocols, we characterize at high resolution the development of the porcine medial entorhinal cortex by tracing neuronal and glial subtypes from mid-gestation to the adult brain to identify the transcriptomic profile of progenitor and adult stellate cells. Importantly, we could confirm the robustness of our data by extracting developmental factors from the identified intermediate stellate cell cluster and implemented these factors to generate putative intermediate stellate cells from human induced pluripotent stem cells. Six transcription factors identified from the stellate cell cluster including RUNX1T1, SOX5, FOXP1, MEF2C, TCF4, EYA2 were overexpressed using a forward programming approach to produce neurons expressing a unique combination of RELN, SATB2, LEF1 and BCL11B observed in stellate cells. Further analyses of the individual transcription factors led to the discovery that FOXP1 is critical in the reprogramming process and omission of RUNX1T1 and EYA2 enhances neuron conversion. Our findings contribute not only to the profiling of cell types within the developing and adult brain{\textquoteright}s medial entorhinal cortex but also provides proof-of-concept for using scRNAseq data to produce entorhinal intermediate stellate cells from human pluripotent stem cells in-vitro.",
keywords = "forward programming, FOXP1, induced pluripotent stem cells, medial entorhinal cortex, stellate cells",
author = "Tobias Bergmann and Yong Liu and Jonathan Skov and Leo Mogus and Julie Lee and Ulrich Pfisterer and Handfield, {Louis Francois} and Andrea Asenjo-Martinez and Irene Lisa-Vargas and Seemann, {Stefan E.} and Lee, {Jimmy Tsz Hang} and Nikolaos Patikas and Kornum, {Birgitte Rahbek} and Mark Denham and Poul Hyttel and Witter, {Menno P.} and Jan Gorodkin and Pers, {Tune H.} and Martin Hemberg and Konstantin Khodosevich and Hall, {Vanessa Jane}",
note = "Publisher Copyright: Copyright {\textcopyright} 2022 Bergmann, Liu, Skov, Mogus, Lee, Pfisterer, Handfield, Asenjo-Martinez, Lisa-Vargas, Seemann, Lee, Patikas, Kornum, Denham, Hyttel, Witter, Gorodkin, Pers, Hemberg, Khodosevich and Hall.",
year = "2022",
doi = "10.3389/fcell.2022.976549",
language = "English",
volume = "10",
journal = "Frontiers in Cell and Developmental Biology",
issn = "2296-634X",
publisher = "Frontiers Media",

}

RIS

TY - JOUR

T1 - Production of human entorhinal stellate cell-like cells by forward programming shows an important role of Foxp1 in reprogramming

AU - Bergmann, Tobias

AU - Liu, Yong

AU - Skov, Jonathan

AU - Mogus, Leo

AU - Lee, Julie

AU - Pfisterer, Ulrich

AU - Handfield, Louis Francois

AU - Asenjo-Martinez, Andrea

AU - Lisa-Vargas, Irene

AU - Seemann, Stefan E.

AU - Lee, Jimmy Tsz Hang

AU - Patikas, Nikolaos

AU - Kornum, Birgitte Rahbek

AU - Denham, Mark

AU - Hyttel, Poul

AU - Witter, Menno P.

AU - Gorodkin, Jan

AU - Pers, Tune H.

AU - Hemberg, Martin

AU - Khodosevich, Konstantin

AU - Hall, Vanessa Jane

N1 - Publisher Copyright: Copyright © 2022 Bergmann, Liu, Skov, Mogus, Lee, Pfisterer, Handfield, Asenjo-Martinez, Lisa-Vargas, Seemann, Lee, Patikas, Kornum, Denham, Hyttel, Witter, Gorodkin, Pers, Hemberg, Khodosevich and Hall.

PY - 2022

Y1 - 2022

N2 - Stellate cells are principal neurons in the entorhinal cortex that contribute to spatial processing. They also play a role in the context of Alzheimer’s disease as they accumulate Amyloid beta early in the disease. Producing human stellate cells from pluripotent stem cells would allow researchers to study early mechanisms of Alzheimer’s disease, however, no protocols currently exist for producing such cells. In order to develop novel stem cell protocols, we characterize at high resolution the development of the porcine medial entorhinal cortex by tracing neuronal and glial subtypes from mid-gestation to the adult brain to identify the transcriptomic profile of progenitor and adult stellate cells. Importantly, we could confirm the robustness of our data by extracting developmental factors from the identified intermediate stellate cell cluster and implemented these factors to generate putative intermediate stellate cells from human induced pluripotent stem cells. Six transcription factors identified from the stellate cell cluster including RUNX1T1, SOX5, FOXP1, MEF2C, TCF4, EYA2 were overexpressed using a forward programming approach to produce neurons expressing a unique combination of RELN, SATB2, LEF1 and BCL11B observed in stellate cells. Further analyses of the individual transcription factors led to the discovery that FOXP1 is critical in the reprogramming process and omission of RUNX1T1 and EYA2 enhances neuron conversion. Our findings contribute not only to the profiling of cell types within the developing and adult brain’s medial entorhinal cortex but also provides proof-of-concept for using scRNAseq data to produce entorhinal intermediate stellate cells from human pluripotent stem cells in-vitro.

AB - Stellate cells are principal neurons in the entorhinal cortex that contribute to spatial processing. They also play a role in the context of Alzheimer’s disease as they accumulate Amyloid beta early in the disease. Producing human stellate cells from pluripotent stem cells would allow researchers to study early mechanisms of Alzheimer’s disease, however, no protocols currently exist for producing such cells. In order to develop novel stem cell protocols, we characterize at high resolution the development of the porcine medial entorhinal cortex by tracing neuronal and glial subtypes from mid-gestation to the adult brain to identify the transcriptomic profile of progenitor and adult stellate cells. Importantly, we could confirm the robustness of our data by extracting developmental factors from the identified intermediate stellate cell cluster and implemented these factors to generate putative intermediate stellate cells from human induced pluripotent stem cells. Six transcription factors identified from the stellate cell cluster including RUNX1T1, SOX5, FOXP1, MEF2C, TCF4, EYA2 were overexpressed using a forward programming approach to produce neurons expressing a unique combination of RELN, SATB2, LEF1 and BCL11B observed in stellate cells. Further analyses of the individual transcription factors led to the discovery that FOXP1 is critical in the reprogramming process and omission of RUNX1T1 and EYA2 enhances neuron conversion. Our findings contribute not only to the profiling of cell types within the developing and adult brain’s medial entorhinal cortex but also provides proof-of-concept for using scRNAseq data to produce entorhinal intermediate stellate cells from human pluripotent stem cells in-vitro.

KW - forward programming

KW - FOXP1

KW - induced pluripotent stem cells

KW - medial entorhinal cortex

KW - stellate cells

U2 - 10.3389/fcell.2022.976549

DO - 10.3389/fcell.2022.976549

M3 - Journal article

C2 - 36046338

AN - SCOPUS:85136896425

VL - 10

JO - Frontiers in Cell and Developmental Biology

JF - Frontiers in Cell and Developmental Biology

SN - 2296-634X

M1 - 976549

ER -

ID: 319247330