Mapping of clonal lineages across developmental stages in human neural differentiation

You, Zhiwen; Wang, Luyue; He, Hui; Wu, Ziyan; Zhang, Xinyue; Xue, Shuaixiang; Xu, Peibo; Hong, Yanhong; Xiong, Man; Wú, Wéi; Chen, Yuejun

doi:10.1016/j.stem.2023.02.007

Cited by 5 publications

(4 citation statements)

References 57 publications

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“…S1a). As an additional validation in parallel to our study, another group also identified APCDD1 as a putative marker of DA progenitor cells through an in vitro lineage tracing-based approach 26 .…”

Section: Identifying Novel Candidate Markers Of Cvm Progenitors From ...supporting

confidence: 63%

“…In a recently published study, You and colleagues strikingly also identified both APCDD1 and TPBG as potentially specific cell surface marker through a different approach of in vitro DA lineage tracing 26 . These two independent converging studies thereby confirm the biological relevance of TPBG and APCDD1 across different cell lines and differentiation methods.…”

Section: Discussionmentioning

confidence: 99%

“…A novel candidate DA progenitor cell surface markeradenomatosis polyposis coli down-regulated 1 (APCDD1) was recently described by another group through transgenic reporter cell line use 26 . In the current study, we independently identified APCDD1 as a candidate VM marker from an in-house single-cell RNA-sequencing (scRNA-seq) dataset, and we proceed to show that APCDD1 is uniquely specific to the caudal fraction of the VM, which gives rise to midbrain DA neurons 27 .…”

Section: Introductionmentioning

confidence: 99%

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APCDD1 outperforms other dopaminergic cell surface markers in benchmarking study

Kirkeby,

Schörling,

Hänninen

et al. 2023

Preprint

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Cell surface markers are useful tools for quality control and enrichment of cellular subtypes, such as the dopaminergic progenitors used in the treatment of Parkinson’s disease (PD). Here, we identified a candidate dopaminergic (DA) progenitor surface marker, APCDD1, and benchmarked its specificity against 7 other previously published markers. APCDD1 correlated with key markers of ventral midbrain DA fate and outperformed the 7 other markers in specificity. Antibody-based sorting for APCDD1 enabled enrichment of DA progenitors and depletion of neighbouring non-DA populations. When sorting from mixed cell populations, only APCDD1+ cells, and not APCDD1- cells, yielded full motoric amelioration after grafting in a rat model of PD, and the APCDD1+ grafts contained a higher proportion of DA neurons co-expressing ventral midbrain markers FOXA2 and LMX1A. Taken together, APCDD1 outperformed previously published surface markers and will be useful for improving the quality control and enrichment of clinically applied cell products for PD.

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Section: Identifying Novel Candidate Markers Of Cvm Progenitors From ...supporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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APCDD1 outperforms other dopaminergic cell surface markers in benchmarking study

Kirkeby,

Schörling,

Hänninen

et al. 2023

Preprint

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“…Neural stem cells, also known as neural progenitor cells or radial glia, hold the key to this enigma 4 . Neural stem cells are the most primitive cell types in brain development, and generate neurons and other cell types during brain development 3,[5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

Spatial ciliary signaling regulates the dorsal/ventral regionalization of human brain organoids

Shimada,

Goto,

Hashimoto

et al. 2024

Preprint

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Regionalization of the brain is a fundamental question in human developmental biology. Primary cilia are known for a critical organelle for dorsal/ventral fate of brain formation in mice, but little is known about how signaling in the primary cilia regulate regionalization of the human brain. Here, we found that signaling in the primary cilia function in regionalization of the brain using brain organoids derived from human induced pluripotent stem (iPS) cells. Deletion of a ciliary GTPase,ARL13B, induced partially ventralized neural stem cells in the dorsal cortical organoids, despite using a guided dorsal cortical organoid differentiation protocol. Mechanistically,ARL13Bknockout (KO) neural stem cells decreased ciliary localization of GPR161, a negative regulator of SHH signaling in primary cilia and increased SONIC HEDGEHOG (SHH) signaling.GPR161deletion also induced ventralized neural stem cells in the dorsal cortical organoids, despite using the guided differentiation protocol.GPR161deletion increased SHH signaling mediated by decreased GLI3 repressor formation. Pharmacological treatment to increase cAMP levels rescued GLI3 repressor formation and the differentiation of dorsal neural stem cells inGPR161KO brain organoids. Importantly, elevating the amount of ciliary cAMP by optogenetics restored the generation of dorsal neural stem cells inGPR161KO brain organoids. These data indicate that spatial ciliary signaling, the ARL13B-GPR161-cAMP axis in primary cilia, is a fundamental regulator of the dorsal/ventral regionalization of the human brain.

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Functional genomics and systems biology in human neuroscience

Konopka,

Bhaduri

2023

Nature

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Mapping of clonal lineages across developmental stages in human neural differentiation

Cited by 5 publications

References 57 publications

APCDD1 outperforms other dopaminergic cell surface markers in benchmarking study

APCDD1 outperforms other dopaminergic cell surface markers in benchmarking study

Spatial ciliary signaling regulates the dorsal/ventral regionalization of human brain organoids

Functional genomics and systems biology in human neuroscience

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