PMID- 36179024
OWN - NLM
STAT- MEDLINE
DCOM- 20221004
LR  - 20231229
IS  - 2375-2548 (Electronic)
IS  - 2375-2548 (Linking)
VI  - 8
IP  - 39
DP  - 2022 Sep 30
TI  - Modular derivation of diverse, regionally discrete human posterior CNS neurons 
      enables discovery of transcriptomic patterns.
PG  - eabn7430
LID - 10.1126/sciadv.abn7430 [doi]
LID - eabn7430
AB  - 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.
FAU - Iyer, Nisha R
AU  - Iyer NR
AUID- ORCID: 0000-0002-9597-0936
AD  - Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 
      USA.
AD  - Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, 
      WI, USA.
FAU - Shin, Junha
AU  - Shin J
AUID- ORCID: 0000-0003-3175-3446
AD  - Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 
      USA.
FAU - Cuskey, Stephanie
AU  - Cuskey S
AD  - Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 
      USA.
FAU - Tian, Yucheng
AU  - Tian Y
AD  - Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 
      USA.
AD  - Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, 
      WI, USA.
FAU - Nicol, Noah R
AU  - Nicol NR
AD  - Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 
      USA.
AD  - Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, 
      WI, USA.
FAU - Doersch, Tessa E
AU  - Doersch TE
AUID- ORCID: 0000-0002-7426-9606
AD  - Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 
      USA.
FAU - Seipel, Frank
AU  - Seipel F
AUID- ORCID: 0000-0001-7823-5561
AD  - Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 
      USA.
AD  - Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, 
      WI, USA.
FAU - McCalla, Sunnie Grace
AU  - McCalla SG
AUID- ORCID: 0000-0003-4292-8694
AD  - Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 
      USA.
AD  - Department of Biostatistics and Medical Informatics, University of 
      Wisconsin-Madison, Madison, WI, USA.
FAU - Roy, Sushmita
AU  - Roy S
AUID- ORCID: 0000-0002-3694-1705
AD  - Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 
      USA.
AD  - Department of Biostatistics and Medical Informatics, University of 
      Wisconsin-Madison, Madison, WI, USA.
FAU - Ashton, Randolph S
AU  - Ashton RS
AUID- ORCID: 0000-0002-6842-7022
AD  - Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 
      USA.
AD  - Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, 
      WI, USA.
LA  - eng
GR  - F32 NS083291/NS/NINDS NIH HHS/United States
GR  - F32 NS106740/NS/NINDS NIH HHS/United States
GR  - R01 GM117339/GM/NIGMS NIH HHS/United States
GR  - T32 GM007133/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20220930
PL  - United States
TA  - Sci Adv
JT  - Science advances
JID - 101653440
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Cell Differentiation/genetics
MH  - Central Nervous System
MH  - Humans
MH  - *Neurons/physiology
MH  - RNA
MH  - *Transcriptome
PMC - PMC9524835
EDAT- 2022/10/01 06:00
MHDA- 2022/10/05 06:00
PMCR- 2022/09/30
CRDT- 2022/09/30 14:04
PHST- 2022/09/30 14:04 [entrez]
PHST- 2022/10/01 06:00 [pubmed]
PHST- 2022/10/05 06:00 [medline]
PHST- 2022/09/30 00:00 [pmc-release]
AID - abn7430 [pii]
AID - 10.1126/sciadv.abn7430 [doi]
PST - ppublish
SO  - Sci Adv. 2022 Sep 30;8(39):eabn7430. doi: 10.1126/sciadv.abn7430. Epub 2022 Sep 
      30.