한빛사논문
- 조회349
Nisha R. Iyer1,2†, Junha Shin1†, Stephanie Cuskey1, Yucheng Tian1,2, Noah R. Nicol1,2, Tessa E. Doersch1, Frank Seipel1,2, Sunnie Grace McCalla1,3, Sushmita Roy1,3*, Randolph S. Ashton1,2*
1Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA. 2Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA. 3Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA.
*Corresponding author.
†These authors contributed equally to this work.
Abstract
Our inability to derive the neuronal diversity that comprises the posterior central nervous system (pCNS) using human pluripotent stem cells (hPSCs) poses an impediment to understanding human neurodevelopment and disease in the hindbrain and spinal cord. Here, we establish a modular, monolayer differentiation paradigm that recapitulates both rostrocaudal (R/C) and dorsoventral (D/V) patterning, enabling derivation of diverse pCNS neurons with discrete regional specificity. First, neuromesodermal progenitors (NMPs) with discrete HOX profiles are converted to pCNS progenitors (pCNSPs). Then, by tuning D/V signaling, pCNSPs are directed to locomotor or somatosensory neurons. Expansive single-cell RNA-sequencing (scRNA-seq) analysis coupled with a novel computational pipeline allowed us to detect hundreds of transcriptional markers within region-specific phenotypes, enabling discovery of gene expression patterns across R/C and D/V developmental axes. These findings highlight the potential of these resources to advance a mechanistic understanding of pCNS development, enhance in vitro models, and inform therapeutic strategies.
논문정보
- Research article
- 2022년 09월 (BRIC 등록일 2022-10-07)
- 국외 연구진
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