Identification of Embryonic Neural Plate Border Stem Cells and Their Generation by Direct Reprogramming from Adult Human Blood Cells

Marc Christian Thier; Oliver Hommerding; Jasper Panten; Roberta Pinna; Diego García-González; Thomas Berger; Philipp Wörsdörfer; Yassen Assenov; Roberta Scognamiglio; Adriana Przybylla; Paul Kaschutnig; Lisa Becker; Michael D Milsom; Anna Jauch; Jochen Utikal; Carl Herrmann; Hannah Monyer; Frank Edenhofer; Andreas Trumpp

doi:10.1016/j.stem.2018.11.015

Identification of Embryonic Neural Plate Border Stem Cells and Their Generation by Direct Reprogramming from Adult Human Blood Cells

Marc Christian Thier, Oliver Hommerding, Jasper Panten, Roberta Pinna, Diego García-González, Thomas Berger, Philipp Wörsdörfer, Yassen Assenov, Roberta Scognamiglio, Adriana Przybylla, Paul Kaschutnig, Lisa Becker, Michael D Milsom, Anna Jauch, Jochen Utikal, Carl Herrmann, Hannah Monyer, Frank Edenhofer, Andreas Trumpp

Basic and Clinical Neuroscience

Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), and DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address: [email protected].
Stem Cell Engineering Group, Institute of Reconstructive Neurobiology, Universität Bonn Life and Brain Center and Hertie Foundation, Sigmund-Freud Strasse 25, 53105 Bonn, Germany.
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), and DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Heidelberg University
Stem Cell and Regenerative Medicine Group, Institute of Anatomy and Cell Biology, Julius-Maximilians-Universität Würzburg, Koellikerstrasse 6, 97070 Würzburg, Germany.
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Division of Experimental Hematology, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), and DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.
Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany.
Stem Cell Engineering Group, Institute of Reconstructive Neurobiology, Universität Bonn Life and Brain Center and Hertie Foundation, Sigmund-Freud Strasse 25, 53105 Bonn, Germany; Leopold-Franzens-University Innsbruck, Institute of Molecular Biology & CMBI, Department Genomics, Stem Cell Biology & Regenerative Medicine, 6020 Innsbruck, Austria.
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), and DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany. Electronic address: [email protected].

Research output: Contribution to journal › Article › peer-review

38 Citations (Scopus)

Abstract

We report the direct reprogramming of both adult human fibroblasts and blood cells into induced neural plate border stem cells (iNBSCs) by ectopic expression of four neural transcription factors. Self-renewing, clonal iNBSCs can be robustly expanded in defined media while retaining multilineage differentiation potential. They generate functional cell types of neural crest and CNS lineages and could be used to model a human pain syndrome via gene editing of SCN9A in iNBSCs. NBSCs can also be derived from human pluripotent stem cells and share functional and molecular features with NBSCs isolated from embryonic day 8.5 (E8.5) mouse neural folds. Single-cell RNA sequencing identified the anterior hindbrain as the origin of mouse NBSCs, with human iNBSCs sharing a similar regional identity. In summary, we identify embryonic NBSCs and report their generation by direct reprogramming in human, which may facilitate insights into neural development and provide a neural stem cell source for applications in regenerative medicine.

Original language	English
Pages (from-to)	166-182.e13
Journal	Cell Stem Cell
Volume	24
Issue number	1
DOIs	https://doi.org/10.1016/j.stem.2018.11.015
Publication status	Published - 3 Jan 2019

Keywords

Adult
Animals
Blood Cells
Cell Differentiation
Cells, Cultured
Cellular Reprogramming
Embryonic Stem Cells/cytology
Humans
Male
Mice
Neural Plate/cytology
Neural Stem Cells/cytology
Neurogenesis
Pluripotent Stem Cells/cytology
Young Adult

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10.1016/j.stem.2018.11.015

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Thier, M. C., Hommerding, O., Panten, J., Pinna, R., García-González, D., Berger, T., Wörsdörfer, P., Assenov, Y., Scognamiglio, R., Przybylla, A., Kaschutnig, P., Becker, L., Milsom, M. D., Jauch, A., Utikal, J., Herrmann, C., Monyer, H., Edenhofer, F., & Trumpp, A. (2019). Identification of Embryonic Neural Plate Border Stem Cells and Their Generation by Direct Reprogramming from Adult Human Blood Cells. Cell Stem Cell, 24(1), 166-182.e13. https://doi.org/10.1016/j.stem.2018.11.015

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title = "Identification of Embryonic Neural Plate Border Stem Cells and Their Generation by Direct Reprogramming from Adult Human Blood Cells",

abstract = "We report the direct reprogramming of both adult human fibroblasts and blood cells into induced neural plate border stem cells (iNBSCs) by ectopic expression of four neural transcription factors. Self-renewing, clonal iNBSCs can be robustly expanded in defined media while retaining multilineage differentiation potential. They generate functional cell types of neural crest and CNS lineages and could be used to model a human pain syndrome via gene editing of SCN9A in iNBSCs. NBSCs can also be derived from human pluripotent stem cells and share functional and molecular features with NBSCs isolated from embryonic day 8.5 (E8.5) mouse neural folds. Single-cell RNA sequencing identified the anterior hindbrain as the origin of mouse NBSCs, with human iNBSCs sharing a similar regional identity. In summary, we identify embryonic NBSCs and report their generation by direct reprogramming in human, which may facilitate insights into neural development and provide a neural stem cell source for applications in regenerative medicine.",

keywords = "Adult, Animals, Blood Cells, Cell Differentiation, Cells, Cultured, Cellular Reprogramming, Embryonic Stem Cells/cytology, Humans, Male, Mice, Neural Plate/cytology, Neural Stem Cells/cytology, Neurogenesis, Pluripotent Stem Cells/cytology, Young Adult",

author = "Thier, {Marc Christian} and Oliver Hommerding and Jasper Panten and Roberta Pinna and Diego Garc{\'i}a-Gonz{\'a}lez and Thomas Berger and Philipp W{\"o}rsd{\"o}rfer and Yassen Assenov and Roberta Scognamiglio and Adriana Przybylla and Paul Kaschutnig and Lisa Becker and Milsom, {Michael D} and Anna Jauch and Jochen Utikal and Carl Herrmann and Hannah Monyer and Frank Edenhofer and Andreas Trumpp",

year = "2019",

month = jan,

day = "3",

doi = "10.1016/j.stem.2018.11.015",

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Thier, MC, Hommerding, O, Panten, J, Pinna, R, García-González, D, Berger, T, Wörsdörfer, P, Assenov, Y, Scognamiglio, R, Przybylla, A, Kaschutnig, P, Becker, L, Milsom, MD, Jauch, A, Utikal, J, Herrmann, C, Monyer, H, Edenhofer, F & Trumpp, A 2019, 'Identification of Embryonic Neural Plate Border Stem Cells and Their Generation by Direct Reprogramming from Adult Human Blood Cells', Cell Stem Cell, vol. 24, no. 1, pp. 166-182.e13. https://doi.org/10.1016/j.stem.2018.11.015

TY - JOUR

T1 - Identification of Embryonic Neural Plate Border Stem Cells and Their Generation by Direct Reprogramming from Adult Human Blood Cells

AU - Thier, Marc Christian

AU - Hommerding, Oliver

AU - Panten, Jasper

AU - Pinna, Roberta

AU - García-González, Diego

AU - Berger, Thomas

AU - Wörsdörfer, Philipp

AU - Assenov, Yassen

AU - Scognamiglio, Roberta

AU - Przybylla, Adriana

AU - Kaschutnig, Paul

AU - Becker, Lisa

AU - Milsom, Michael D

AU - Jauch, Anna

AU - Utikal, Jochen

AU - Herrmann, Carl

AU - Monyer, Hannah

AU - Edenhofer, Frank

AU - Trumpp, Andreas

PY - 2019/1/3

Y1 - 2019/1/3

N2 - We report the direct reprogramming of both adult human fibroblasts and blood cells into induced neural plate border stem cells (iNBSCs) by ectopic expression of four neural transcription factors. Self-renewing, clonal iNBSCs can be robustly expanded in defined media while retaining multilineage differentiation potential. They generate functional cell types of neural crest and CNS lineages and could be used to model a human pain syndrome via gene editing of SCN9A in iNBSCs. NBSCs can also be derived from human pluripotent stem cells and share functional and molecular features with NBSCs isolated from embryonic day 8.5 (E8.5) mouse neural folds. Single-cell RNA sequencing identified the anterior hindbrain as the origin of mouse NBSCs, with human iNBSCs sharing a similar regional identity. In summary, we identify embryonic NBSCs and report their generation by direct reprogramming in human, which may facilitate insights into neural development and provide a neural stem cell source for applications in regenerative medicine.

AB - We report the direct reprogramming of both adult human fibroblasts and blood cells into induced neural plate border stem cells (iNBSCs) by ectopic expression of four neural transcription factors. Self-renewing, clonal iNBSCs can be robustly expanded in defined media while retaining multilineage differentiation potential. They generate functional cell types of neural crest and CNS lineages and could be used to model a human pain syndrome via gene editing of SCN9A in iNBSCs. NBSCs can also be derived from human pluripotent stem cells and share functional and molecular features with NBSCs isolated from embryonic day 8.5 (E8.5) mouse neural folds. Single-cell RNA sequencing identified the anterior hindbrain as the origin of mouse NBSCs, with human iNBSCs sharing a similar regional identity. In summary, we identify embryonic NBSCs and report their generation by direct reprogramming in human, which may facilitate insights into neural development and provide a neural stem cell source for applications in regenerative medicine.

KW - Adult

KW - Animals

KW - Blood Cells

KW - Cell Differentiation

KW - Cells, Cultured

KW - Cellular Reprogramming

KW - Embryonic Stem Cells/cytology

KW - Humans

KW - Male

KW - Mice

KW - Neural Plate/cytology

KW - Neural Stem Cells/cytology

KW - Neurogenesis

KW - Pluripotent Stem Cells/cytology

KW - Young Adult

U2 - 10.1016/j.stem.2018.11.015

DO - 10.1016/j.stem.2018.11.015

M3 - Article

C2 - 30581079

SN - 1934-5909

VL - 24

SP - 166-182.e13

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 1

ER -

Identification of Embryonic Neural Plate Border Stem Cells and Their Generation by Direct Reprogramming from Adult Human Blood Cells

Abstract

Keywords

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