Nests of dividing neuroblasts sustain interneuron production for the developing human brain

Mercedes F. Paredes; Cristina Mora; Quetzal Flores-Ramirez; Arantxa Cebrian-Silla; Ashley Del Dosso; Phil Larimer; Jiapei Chen; Gugene Kang; Susana Gonzalez Granero; Eric Garcia; Julia Chu; Ryan Delgado; Jennifer A. Cotter; Vivian Tang; Julien Spatazza; Kirsten Obernier; Jaime Ferrer Lozano; Maximo Vento; Julia Scott; Colin Studholme; Tomasz J. Nowakowski; Arnold R. Kriegstein; Michael C. Oldham; Andrea Hasenstaub; Jose Manuel Garcia-Verdugo; Arturo Alvarez-Buylla; Eric J. Huang

doi:10.1126/science.abk2346

Nests of dividing neuroblasts sustain interneuron production for the developing human brain

Mercedes F. Paredes
, Cristina Mora
, Quetzal Flores-Ramirez
, Arantxa Cebrian-Silla
, Ashley Del Dosso
, Phil Larimer
, Jiapei Chen
, Gugene Kang
, Susana Gonzalez Granero
, Eric Garcia
, Julia Chu
, Ryan Delgado
, Jennifer A. Cotter
, Vivian Tang
, Julien Spatazza
, Kirsten Obernier
, Jaime Ferrer Lozano
, Maximo Vento
, Julia Scott
, Colin Studholme

Tomasz J. Nowakowski, Arnold R. Kriegstein, Michael C. Oldham, Andrea Hasenstaub, Jose Manuel Garcia-Verdugo, Arturo Alvarez-Buylla, Eric J. Huang

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

37 Scopus citations

Abstract

The human cortex contains inhibitory interneurons derived from the medial ganglionic eminence (MGE), a germinal zone in the embryonic ventral forebrain. How this germinal zone generates sufficient interneurons for the human brain remains unclear. We found that the human MGE (hMGE) contains nests of proliferative neuroblasts with ultrastructural and transcriptomic features that distinguish them from other progenitors in the hMGE. When dissociated hMGE cells are transplanted into the neonatal mouse brain, they reform into nests containing proliferating neuroblasts that generate young neurons that migrate extensively into the mouse forebrain and mature into different subtypes of functional interneurons. Together, these results indicate that the nest organization and sustained proliferation of neuroblasts in the hMGE provide a mechanism for the extended production of interneurons for the human forebrain.

Original language	English
Article number	eabk2346
Journal	Science
Volume	375
Issue number	6579
DOIs	https://doi.org/10.1126/science.abk2346
State	Published - Jan 28 2022

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Paredes, M. F., Mora, C., Flores-Ramirez, Q., Cebrian-Silla, A., Del Dosso, A., Larimer, P., Chen, J., Kang, G., Granero, S. G., Garcia, E., Chu, J., Delgado, R., Cotter, J. A., Tang, V., Spatazza, J., Obernier, K., Lozano, J. F., Vento, M., Scott, J., ... Huang, E. J. (2022). Nests of dividing neuroblasts sustain interneuron production for the developing human brain. Science, 375(6579), Article eabk2346. https://doi.org/10.1126/science.abk2346

@article{160a4a6140c743c295a5c6c3bc0c70cb,

title = "Nests of dividing neuroblasts sustain interneuron production for the developing human brain",

abstract = "The human cortex contains inhibitory interneurons derived from the medial ganglionic eminence (MGE), a germinal zone in the embryonic ventral forebrain. How this germinal zone generates sufficient interneurons for the human brain remains unclear. We found that the human MGE (hMGE) contains nests of proliferative neuroblasts with ultrastructural and transcriptomic features that distinguish them from other progenitors in the hMGE. When dissociated hMGE cells are transplanted into the neonatal mouse brain, they reform into nests containing proliferating neuroblasts that generate young neurons that migrate extensively into the mouse forebrain and mature into different subtypes of functional interneurons. Together, these results indicate that the nest organization and sustained proliferation of neuroblasts in the hMGE provide a mechanism for the extended production of interneurons for the human forebrain.",

author = "Paredes, \{Mercedes F.\} and Cristina Mora and Quetzal Flores-Ramirez and Arantxa Cebrian-Silla and \{Del Dosso\}, Ashley and Phil Larimer and Jiapei Chen and Gugene Kang and Granero, \{Susana Gonzalez\} and Eric Garcia and Julia Chu and Ryan Delgado and Cotter, \{Jennifer A.\} and Vivian Tang and Julien Spatazza and Kirsten Obernier and Lozano, \{Jaime Ferrer\} and Maximo Vento and Julia Scott and Colin Studholme and Nowakowski, \{Tomasz J.\} and Kriegstein, \{Arnold R.\} and Oldham, \{Michael C.\} and Andrea Hasenstaub and Garcia-Verdugo, \{Jose Manuel\} and Arturo Alvarez-Buylla and Huang, \{Eric J.\}",

year = "2022",

month = jan,

day = "28",

doi = "10.1126/science.abk2346",

language = "English",

volume = "375",

journal = "Science",

issn = "0036-8075",

number = "6579",

}

Paredes, MF, Mora, C, Flores-Ramirez, Q, Cebrian-Silla, A, Del Dosso, A, Larimer, P, Chen, J, Kang, G, Granero, SG, Garcia, E, Chu, J, Delgado, R, Cotter, JA, Tang, V, Spatazza, J, Obernier, K, Lozano, JF, Vento, M, Scott, J, Studholme, C, Nowakowski, TJ, Kriegstein, AR, Oldham, MC, Hasenstaub, A, Garcia-Verdugo, JM, Alvarez-Buylla, A & Huang, EJ 2022, 'Nests of dividing neuroblasts sustain interneuron production for the developing human brain', Science, vol. 375, no. 6579, eabk2346. https://doi.org/10.1126/science.abk2346

TY - JOUR

T1 - Nests of dividing neuroblasts sustain interneuron production for the developing human brain

AU - Paredes, Mercedes F.

AU - Mora, Cristina

AU - Flores-Ramirez, Quetzal

AU - Cebrian-Silla, Arantxa

AU - Del Dosso, Ashley

AU - Larimer, Phil

AU - Chen, Jiapei

AU - Kang, Gugene

AU - Granero, Susana Gonzalez

AU - Garcia, Eric

AU - Chu, Julia

AU - Delgado, Ryan

AU - Cotter, Jennifer A.

AU - Tang, Vivian

AU - Spatazza, Julien

AU - Obernier, Kirsten

AU - Lozano, Jaime Ferrer

AU - Vento, Maximo

AU - Scott, Julia

AU - Studholme, Colin

AU - Nowakowski, Tomasz J.

AU - Kriegstein, Arnold R.

AU - Oldham, Michael C.

AU - Hasenstaub, Andrea

AU - Garcia-Verdugo, Jose Manuel

AU - Alvarez-Buylla, Arturo

AU - Huang, Eric J.

PY - 2022/1/28

Y1 - 2022/1/28

N2 - The human cortex contains inhibitory interneurons derived from the medial ganglionic eminence (MGE), a germinal zone in the embryonic ventral forebrain. How this germinal zone generates sufficient interneurons for the human brain remains unclear. We found that the human MGE (hMGE) contains nests of proliferative neuroblasts with ultrastructural and transcriptomic features that distinguish them from other progenitors in the hMGE. When dissociated hMGE cells are transplanted into the neonatal mouse brain, they reform into nests containing proliferating neuroblasts that generate young neurons that migrate extensively into the mouse forebrain and mature into different subtypes of functional interneurons. Together, these results indicate that the nest organization and sustained proliferation of neuroblasts in the hMGE provide a mechanism for the extended production of interneurons for the human forebrain.

AB - The human cortex contains inhibitory interneurons derived from the medial ganglionic eminence (MGE), a germinal zone in the embryonic ventral forebrain. How this germinal zone generates sufficient interneurons for the human brain remains unclear. We found that the human MGE (hMGE) contains nests of proliferative neuroblasts with ultrastructural and transcriptomic features that distinguish them from other progenitors in the hMGE. When dissociated hMGE cells are transplanted into the neonatal mouse brain, they reform into nests containing proliferating neuroblasts that generate young neurons that migrate extensively into the mouse forebrain and mature into different subtypes of functional interneurons. Together, these results indicate that the nest organization and sustained proliferation of neuroblasts in the hMGE provide a mechanism for the extended production of interneurons for the human forebrain.

UR - https://www.scopus.com/pages/publications/85123616509

U2 - 10.1126/science.abk2346

DO - 10.1126/science.abk2346

M3 - Article

C2 - 35084970

AN - SCOPUS:85123616509

SN - 0036-8075

VL - 375

JO - Science

JF - Science

IS - 6579

M1 - eabk2346

ER -

Nests of dividing neuroblasts sustain interneuron production for the developing human brain

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