Trithorax maintains the functional heterogeneity of neural stem cells through the transcription factor Buttonhead
Abstract
The mechanisms that maintain the functional heterogeneity of stem cells, which generates diverse differentiated cell types required for organogenesis, are not understood. In this study, we report that Trithorax (Trx) actively maintains the heterogeneity of neural stem cells (neuroblasts) in the developing Drosophila larval brain. trx mutant type II neuroblasts gradually adopt a type I neuroblast functional identity, losing the competence to generate intermediate neural progenitors (INPs) and directly generating differentiated cells. Trx regulates a type II neuroblast functional identity in part by maintaining chromatin in the buttonhead (btd) locus in an active state through the histone methyltransferase activity of the SET1/MLL complex. Consistently, btd is necessary and sufficient for eliciting a type II neuroblast functional identity. Furthermore, over-expression of btd restores the competence to generate INPs in trx mutant type II neuroblasts. Thus, Trx instructs a type II neuroblast functional identity by epigenetically promoting Btd expression, thereby maintaining neuroblast functional heterogeneity.
- Authors:
-
- Univ. of Michigan Medical School, Ann Arbor, MI (United States)
- Publication Date:
- Research Org.:
- Univ. of Washington, Seattle, WA (United States); Univ. of Michigan Medical School, Ann Arbor, MI (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC); Japan Society for the Promotion of Science (JSPS); National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS)
- OSTI Identifier:
- 1628818
- Grant/Contract Number:
- FG02-00ER41132; T32-GM007315; R01-GM092818
- Resource Type:
- Accepted Manuscript
- Journal Name:
- eLife
- Additional Journal Information:
- Journal Volume: 3; Journal ID: ISSN 2050-084X
- Publisher:
- eLife Sciences Publications, Ltd.
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Life Sciences & Biomedicine - Other Topics; Research Article; Stem Cells And Regenerative Medicine; Neuroblast; Neural Stem Cell; Trithorax; Larval Brain; Intermediate Neural Progenitor
Citation Formats
Komori, Hideyuki, Xiao, Qi, Janssens, Derek H., Dou, Yali, and Lee, Cheng-Yu. Trithorax maintains the functional heterogeneity of neural stem cells through the transcription factor Buttonhead. United States: N. p., 2014.
Web. doi:10.7554/elife.03502.
Komori, Hideyuki, Xiao, Qi, Janssens, Derek H., Dou, Yali, & Lee, Cheng-Yu. Trithorax maintains the functional heterogeneity of neural stem cells through the transcription factor Buttonhead. United States. https://doi.org/10.7554/elife.03502
Komori, Hideyuki, Xiao, Qi, Janssens, Derek H., Dou, Yali, and Lee, Cheng-Yu. Mon .
"Trithorax maintains the functional heterogeneity of neural stem cells through the transcription factor Buttonhead". United States. https://doi.org/10.7554/elife.03502. https://www.osti.gov/servlets/purl/1628818.
@article{osti_1628818,
title = {Trithorax maintains the functional heterogeneity of neural stem cells through the transcription factor Buttonhead},
author = {Komori, Hideyuki and Xiao, Qi and Janssens, Derek H. and Dou, Yali and Lee, Cheng-Yu},
abstractNote = {The mechanisms that maintain the functional heterogeneity of stem cells, which generates diverse differentiated cell types required for organogenesis, are not understood. In this study, we report that Trithorax (Trx) actively maintains the heterogeneity of neural stem cells (neuroblasts) in the developing Drosophila larval brain. trx mutant type II neuroblasts gradually adopt a type I neuroblast functional identity, losing the competence to generate intermediate neural progenitors (INPs) and directly generating differentiated cells. Trx regulates a type II neuroblast functional identity in part by maintaining chromatin in the buttonhead (btd) locus in an active state through the histone methyltransferase activity of the SET1/MLL complex. Consistently, btd is necessary and sufficient for eliciting a type II neuroblast functional identity. Furthermore, over-expression of btd restores the competence to generate INPs in trx mutant type II neuroblasts. Thus, Trx instructs a type II neuroblast functional identity by epigenetically promoting Btd expression, thereby maintaining neuroblast functional heterogeneity.},
doi = {10.7554/elife.03502},
journal = {eLife},
number = ,
volume = 3,
place = {United States},
year = {Mon Oct 06 00:00:00 EDT 2014},
month = {Mon Oct 06 00:00:00 EDT 2014}
}
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