Human fetal brain self-organizes into long-term expanding organoids

Delilah Hendriks; Anna Pagliaro; Francesco Andreatta; Ziliang Ma; Joey van Giessen; Simone Massalini; Carmen López-Iglesias; Gijs J.F. van Son; Jeff DeMartino; J. Mirjam A. Damen; Iris Zoutendijk; Nadzeya Staliarova; Annelien L. Bredenoord; Frank C.P. Holstege; Peter J. Peters; Thanasis Margaritis; Susana Chuva de Sousa Lopes; Wei Wu; Hans Clevers; Benedetta Artegiani

doi:10.1016/j.cell.2023.12.012

Human fetal brain self-organizes into long-term expanding organoids

Delilah Hendriks^*, Anna Pagliaro, Francesco Andreatta, Ziliang Ma, Joey van Giessen, Simone Massalini, Carmen López-Iglesias, Gijs J.F. van Son, Jeff DeMartino, J. Mirjam A. Damen, Iris Zoutendijk, Nadzeya Staliarova, Annelien L. Bredenoord, Frank C.P. Holstege, Peter J. Peters, Thanasis Margaritis, Susana Chuva de Sousa Lopes, Wei Wu, Hans Clevers^*, Benedetta Artegiani^*

^*Corresponding author for this work

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

Abstract

Human brain development involves an orchestrated, massive neural progenitor expansion while a multi-cellular tissue architecture is established. Continuously expanding organoids can be grown directly from multiple somatic tissues, yet to date, brain organoids can solely be established from pluripotent stem cells. Here, we show that healthy human fetal brain in vitro self-organizes into organoids (FeBOs), phenocopying aspects of in vivo cellular heterogeneity and complex organization. FeBOs can be expanded over long time periods. FeBO growth requires maintenance of tissue integrity, which ensures production of a tissue-like extracellular matrix (ECM) niche, ultimately endowing FeBO expansion. FeBO lines derived from different areas of the central nervous system (CNS), including dorsal and ventral forebrain, preserve their regional identity and allow to probe aspects of positional identity. Using CRISPR-Cas9, we showcase the generation of syngeneic mutant FeBO lines for the study of brain cancer. Taken together, FeBOs constitute a complementary CNS organoid platform.

Original language	English
Article number	e38
Pages (from-to)	712-732
Number of pages	21
Journal	Cell
Volume	187
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2023.12.012
Publication status	Published - 1 Feb 2024

Bibliographical note

Publisher Copyright:
© 2023 The Author(s)

Funding

We thank Willine van de Wetering and Eduard Bodewes for technical support, Dr. Wim de Lau and Joost Wijnakker for discussions, and Drs. Marcel Kool and Jens Bunt for resources. We thank Drs. Steve Lisgo and Nita Solanky and their teams at HDBR for their invaluable support. D.H. is supported by an NWO VENI grant (VI.Veni.212.134). Part of this work is supported by an NWO Open Competition Science-M grant (B.A.).

Funders	Funder number
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	VI.Veni.212.134
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Human Developmental Biology Resource

Keywords

brain cancer
brain development
CRISPR-Cas9
ECM
human fetal brain
morphogens
organoids
regional identity
tissue culture
tumor modeling

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.cell.2023.12.012Licence: CC BY

1-s2.0-S0092867423013442-mainFinal published version, 37.7 MBLicence: CC BY

Cite this

Hendriks, D., Pagliaro, A., Andreatta, F., Ma, Z., van Giessen, J., Massalini, S., López-Iglesias, C., van Son, G. J. F., DeMartino, J., Damen, J. M. A., Zoutendijk, I., Staliarova, N., Bredenoord, A. L., Holstege, F. C. P., Peters, P. J., Margaritis, T., Chuva de Sousa Lopes, S., Wu, W., Clevers, H., & Artegiani, B. (2024). Human fetal brain self-organizes into long-term expanding organoids. Cell, 187(3), 712-732. Article e38. https://doi.org/10.1016/j.cell.2023.12.012

@article{7beb7a9cb91a4a6d922ae5b9e6fb544e,

title = "Human fetal brain self-organizes into long-term expanding organoids",

abstract = "Human brain development involves an orchestrated, massive neural progenitor expansion while a multi-cellular tissue architecture is established. Continuously expanding organoids can be grown directly from multiple somatic tissues, yet to date, brain organoids can solely be established from pluripotent stem cells. Here, we show that healthy human fetal brain in vitro self-organizes into organoids (FeBOs), phenocopying aspects of in vivo cellular heterogeneity and complex organization. FeBOs can be expanded over long time periods. FeBO growth requires maintenance of tissue integrity, which ensures production of a tissue-like extracellular matrix (ECM) niche, ultimately endowing FeBO expansion. FeBO lines derived from different areas of the central nervous system (CNS), including dorsal and ventral forebrain, preserve their regional identity and allow to probe aspects of positional identity. Using CRISPR-Cas9, we showcase the generation of syngeneic mutant FeBO lines for the study of brain cancer. Taken together, FeBOs constitute a complementary CNS organoid platform.",

keywords = "brain cancer, brain development, CRISPR-Cas9, ECM, human fetal brain, morphogens, organoids, regional identity, tissue culture, tumor modeling",

author = "Delilah Hendriks and Anna Pagliaro and Francesco Andreatta and Ziliang Ma and {van Giessen}, Joey and Simone Massalini and Carmen L{\'o}pez-Iglesias and {van Son}, {Gijs J.F.} and Jeff DeMartino and Damen, {J. Mirjam A.} and Iris Zoutendijk and Nadzeya Staliarova and Bredenoord, {Annelien L.} and Holstege, {Frank C.P.} and Peters, {Peter J.} and Thanasis Margaritis and {Chuva de Sousa Lopes}, Susana and Wei Wu and Hans Clevers and Benedetta Artegiani",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2024",

month = feb,

day = "1",

doi = "10.1016/j.cell.2023.12.012",

language = "English",

volume = "187",

pages = "712--732",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier BV",

number = "3",

}

Hendriks, D, Pagliaro, A, Andreatta, F, Ma, Z, van Giessen, J, Massalini, S, López-Iglesias, C, van Son, GJF, DeMartino, J, Damen, JMA, Zoutendijk, I, Staliarova, N, Bredenoord, AL, Holstege, FCP, Peters, PJ, Margaritis, T, Chuva de Sousa Lopes, S, Wu, W, Clevers, H & Artegiani, B 2024, 'Human fetal brain self-organizes into long-term expanding organoids', Cell, vol. 187, no. 3, e38, pp. 712-732. https://doi.org/10.1016/j.cell.2023.12.012

TY - JOUR

T1 - Human fetal brain self-organizes into long-term expanding organoids

AU - Hendriks, Delilah

AU - Pagliaro, Anna

AU - Andreatta, Francesco

AU - Ma, Ziliang

AU - van Giessen, Joey

AU - Massalini, Simone

AU - López-Iglesias, Carmen

AU - van Son, Gijs J.F.

AU - DeMartino, Jeff

AU - Damen, J. Mirjam A.

AU - Zoutendijk, Iris

AU - Staliarova, Nadzeya

AU - Bredenoord, Annelien L.

AU - Holstege, Frank C.P.

AU - Peters, Peter J.

AU - Margaritis, Thanasis

AU - Chuva de Sousa Lopes, Susana

AU - Wu, Wei

AU - Clevers, Hans

AU - Artegiani, Benedetta

PY - 2024/2/1

Y1 - 2024/2/1

N2 - Human brain development involves an orchestrated, massive neural progenitor expansion while a multi-cellular tissue architecture is established. Continuously expanding organoids can be grown directly from multiple somatic tissues, yet to date, brain organoids can solely be established from pluripotent stem cells. Here, we show that healthy human fetal brain in vitro self-organizes into organoids (FeBOs), phenocopying aspects of in vivo cellular heterogeneity and complex organization. FeBOs can be expanded over long time periods. FeBO growth requires maintenance of tissue integrity, which ensures production of a tissue-like extracellular matrix (ECM) niche, ultimately endowing FeBO expansion. FeBO lines derived from different areas of the central nervous system (CNS), including dorsal and ventral forebrain, preserve their regional identity and allow to probe aspects of positional identity. Using CRISPR-Cas9, we showcase the generation of syngeneic mutant FeBO lines for the study of brain cancer. Taken together, FeBOs constitute a complementary CNS organoid platform.

AB - Human brain development involves an orchestrated, massive neural progenitor expansion while a multi-cellular tissue architecture is established. Continuously expanding organoids can be grown directly from multiple somatic tissues, yet to date, brain organoids can solely be established from pluripotent stem cells. Here, we show that healthy human fetal brain in vitro self-organizes into organoids (FeBOs), phenocopying aspects of in vivo cellular heterogeneity and complex organization. FeBOs can be expanded over long time periods. FeBO growth requires maintenance of tissue integrity, which ensures production of a tissue-like extracellular matrix (ECM) niche, ultimately endowing FeBO expansion. FeBO lines derived from different areas of the central nervous system (CNS), including dorsal and ventral forebrain, preserve their regional identity and allow to probe aspects of positional identity. Using CRISPR-Cas9, we showcase the generation of syngeneic mutant FeBO lines for the study of brain cancer. Taken together, FeBOs constitute a complementary CNS organoid platform.

KW - brain cancer

KW - brain development

KW - CRISPR-Cas9

KW - ECM

KW - human fetal brain

KW - morphogens

KW - organoids

KW - regional identity

KW - tissue culture

KW - tumor modeling

UR - http://www.scopus.com/inward/record.url?scp=85183932589&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2023.12.012

DO - 10.1016/j.cell.2023.12.012

M3 - Article

C2 - 38194967

AN - SCOPUS:85183932589

SN - 0092-8674

VL - 187

SP - 712

EP - 732

JO - Cell

JF - Cell

IS - 3

M1 - e38

ER -

Human fetal brain self-organizes into long-term expanding organoids

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this