TY - JOUR
T1 - SNIP1 and PRC2 coordinate cell fates of neural progenitors during brain development
AU - Matsui, Yurika
AU - Djekidel, Mohamed Nadhir
AU - Lindsay, Katherine
AU - Samir, Parimal
AU - Connolly, Nina
AU - Wu, Gang
AU - Yang, Xiaoyang
AU - Fan, Yiping
AU - Xu, Beisi
AU - Peng, Jamy C.
N1 - Funding Information:
The authors thank V. Shanker for editing the manuscript; J. Houston and K. Lowe for FACS; M. Evans, I. Lam, I. Chapman, H. Chen, and E. Rivera-Peraza for experimental assistance. RNAscope was performed by the Comparative Histology Core at SJCRH. Sequencing was performed at the Harwell Center for Biotechnology and images were acquired at the Cell & Tissue Imaging Center, both of which are supported by SJCRH and NCI P30 (CA021765). M.N.D, Y.F., and B.X. are supported by NCI P30 grant (CA21765). This work is funded by the American Lebanese Syrian Associated Charities, American Cancer Society (132096-RSG-18-032-01-DDC), and NIH (1R01GM134358-01). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funding Information:
The authors thank V. Shanker for editing the manuscript; J. Houston and K. Lowe for FACS; M. Evans, I. Lam, I. Chapman, H. Chen, and E. Rivera-Peraza for experimental assistance. RNAscope was performed by the Comparative Histology Core at SJCRH. Sequencing was performed at the Harwell Center for Biotechnology and images were acquired at the Cell & Tissue Imaging Center, both of which are supported by SJCRH and NCI P30 (CA021765). M.N.D, Y.F., and B.X. are supported by NCI P30 grant (CA21765). This work is funded by the American Lebanese Syrian Associated Charities, American Cancer Society (132096-RSG-18-032-01-DDC), and NIH (1R01GM134358-01). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/12
Y1 - 2023/12
N2 - Stem cell survival versus death is a developmentally programmed process essential for morphogenesis, sizing, and quality control of genome integrity and cell fates. Cell death is pervasive during development, but its programming is little known. Here, we report that Smad nuclear interacting protein 1 (SNIP1) promotes neural progenitor cell survival and neurogenesis and is, therefore, integral to brain development. The SNIP1-depleted brain exhibits dysplasia with robust induction of caspase 9-dependent apoptosis. Mechanistically, SNIP1 regulates target genes that promote cell survival and neurogenesis, and its activities are influenced by TGFβ and NFκB signaling pathways. Further, SNIP1 facilitates the genomic occupancy of Polycomb complex PRC2 and instructs H3K27me3 turnover at target genes. Depletion of PRC2 is sufficient to reduce apoptosis and brain dysplasia and to partially restore genetic programs in the SNIP1-depleted brain in vivo. These findings suggest a loci-specific regulation of PRC2 and H3K27 marks to toggle cell survival and death in the developing brain.
AB - Stem cell survival versus death is a developmentally programmed process essential for morphogenesis, sizing, and quality control of genome integrity and cell fates. Cell death is pervasive during development, but its programming is little known. Here, we report that Smad nuclear interacting protein 1 (SNIP1) promotes neural progenitor cell survival and neurogenesis and is, therefore, integral to brain development. The SNIP1-depleted brain exhibits dysplasia with robust induction of caspase 9-dependent apoptosis. Mechanistically, SNIP1 regulates target genes that promote cell survival and neurogenesis, and its activities are influenced by TGFβ and NFκB signaling pathways. Further, SNIP1 facilitates the genomic occupancy of Polycomb complex PRC2 and instructs H3K27me3 turnover at target genes. Depletion of PRC2 is sufficient to reduce apoptosis and brain dysplasia and to partially restore genetic programs in the SNIP1-depleted brain in vivo. These findings suggest a loci-specific regulation of PRC2 and H3K27 marks to toggle cell survival and death in the developing brain.
UR - http://www.scopus.com/inward/record.url?scp=85167372126&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85167372126&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-40487-4
DO - 10.1038/s41467-023-40487-4
M3 - Article
C2 - 37553330
AN - SCOPUS:85167372126
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4754
ER -