Cochlear organoids reveal transcriptional programs of postnatal hair cell differentiation from supporting cells

Gurmannat Kalra; Danielle Lenz; Dunia Abdul-Aziz; Craig Hanna; Mahashweta Basu; Brian R. Herb; Carlo Colantuoni; Beatrice Milon; Madhurima Saxena; Amol C. Shetty; Ronna Hertzano; Ramesh A. Shivdasani; Seth A. Ament; Albert S.B. Edge

doi:10.1016/j.celrep.2023.113421

Cochlear organoids reveal transcriptional programs of postnatal hair cell differentiation from supporting cells

Gurmannat Kalra, Danielle Lenz, Dunia Abdul-Aziz, Craig Hanna, Mahashweta Basu, Brian R. Herb, Carlo Colantuoni, Beatrice Milon, Madhurima Saxena, Amol C. Shetty, Ronna Hertzano, Ramesh A. Shivdasani, Seth A. Ament, Albert S.B. Edge

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

Abstract

We explore the changes in chromatin accessibility and transcriptional programs for cochlear hair cell differentiation from postmitotic supporting cells using organoids from postnatal cochlea. The organoids contain cells with transcriptional signatures of differentiating vestibular and cochlear hair cells. Construction of trajectories identifies Lgr5+ cells as progenitors for hair cells, and the genomic data reveal gene regulatory networks leading to hair cells. We validate these networks, demonstrating dynamic changes both in expression and predicted binding sites of transcription factors (TFs) during organoid differentiation. We identify known regulators of hair cell development, Atoh1, Pou4f3, and Gfi1, and the analysis predicts the regulatory factors Tcf4, an E-protein and heterodimerization partner of Atoh1, and Ddit3, a CCAAT/enhancer-binding protein (C/EBP) that represses Hes1 and activates transcription of Wnt-signaling-related genes. Deciphering the signals for hair cell regeneration from mammalian cochlear supporting cells reveals candidates for hair cell (HC) regeneration, which is limited in the adult.

Original language	English (US)
Article number	113421
Journal	Cell Reports
Volume	42
Issue number	11
DOIs	https://doi.org/10.1016/j.celrep.2023.113421
State	Published - Nov 28 2023
Externally published	Yes

Keywords

ATAC sequencing
CP: Stem cell research
cochlea
gene expression analysis
sensory hair cells
single-cell RNA sequencing

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.celrep.2023.113421

Cite this

Kalra, G., Lenz, D., Abdul-Aziz, D., Hanna, C., Basu, M., Herb, B. R., Colantuoni, C., Milon, B., Saxena, M., Shetty, A. C., Hertzano, R., Shivdasani, R. A., Ament, S. A., & Edge, A. S. B. (2023). Cochlear organoids reveal transcriptional programs of postnatal hair cell differentiation from supporting cells. Cell Reports, 42(11), Article 113421. https://doi.org/10.1016/j.celrep.2023.113421

@article{09498d96c57a46e09dd9830bf144eccc,

title = "Cochlear organoids reveal transcriptional programs of postnatal hair cell differentiation from supporting cells",

abstract = "We explore the changes in chromatin accessibility and transcriptional programs for cochlear hair cell differentiation from postmitotic supporting cells using organoids from postnatal cochlea. The organoids contain cells with transcriptional signatures of differentiating vestibular and cochlear hair cells. Construction of trajectories identifies Lgr5+ cells as progenitors for hair cells, and the genomic data reveal gene regulatory networks leading to hair cells. We validate these networks, demonstrating dynamic changes both in expression and predicted binding sites of transcription factors (TFs) during organoid differentiation. We identify known regulators of hair cell development, Atoh1, Pou4f3, and Gfi1, and the analysis predicts the regulatory factors Tcf4, an E-protein and heterodimerization partner of Atoh1, and Ddit3, a CCAAT/enhancer-binding protein (C/EBP) that represses Hes1 and activates transcription of Wnt-signaling-related genes. Deciphering the signals for hair cell regeneration from mammalian cochlear supporting cells reveals candidates for hair cell (HC) regeneration, which is limited in the adult.",

keywords = "ATAC sequencing, CP: Stem cell research, cochlea, gene expression analysis, sensory hair cells, single-cell RNA sequencing",

author = "Gurmannat Kalra and Danielle Lenz and Dunia Abdul-Aziz and Craig Hanna and Mahashweta Basu and Herb, {Brian R.} and Carlo Colantuoni and Beatrice Milon and Madhurima Saxena and Shetty, {Amol C.} and Ronna Hertzano and Shivdasani, {Ramesh A.} and Ament, {Seth A.} and Edge, {Albert S.B.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = nov,

day = "28",

doi = "10.1016/j.celrep.2023.113421",

language = "English (US)",

volume = "42",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "11",

}

TY - JOUR

T1 - Cochlear organoids reveal transcriptional programs of postnatal hair cell differentiation from supporting cells

AU - Kalra, Gurmannat

AU - Lenz, Danielle

AU - Abdul-Aziz, Dunia

AU - Hanna, Craig

AU - Basu, Mahashweta

AU - Herb, Brian R.

AU - Colantuoni, Carlo

AU - Milon, Beatrice

AU - Saxena, Madhurima

AU - Shetty, Amol C.

AU - Hertzano, Ronna

AU - Shivdasani, Ramesh A.

AU - Ament, Seth A.

AU - Edge, Albert S.B.

PY - 2023/11/28

Y1 - 2023/11/28

N2 - We explore the changes in chromatin accessibility and transcriptional programs for cochlear hair cell differentiation from postmitotic supporting cells using organoids from postnatal cochlea. The organoids contain cells with transcriptional signatures of differentiating vestibular and cochlear hair cells. Construction of trajectories identifies Lgr5+ cells as progenitors for hair cells, and the genomic data reveal gene regulatory networks leading to hair cells. We validate these networks, demonstrating dynamic changes both in expression and predicted binding sites of transcription factors (TFs) during organoid differentiation. We identify known regulators of hair cell development, Atoh1, Pou4f3, and Gfi1, and the analysis predicts the regulatory factors Tcf4, an E-protein and heterodimerization partner of Atoh1, and Ddit3, a CCAAT/enhancer-binding protein (C/EBP) that represses Hes1 and activates transcription of Wnt-signaling-related genes. Deciphering the signals for hair cell regeneration from mammalian cochlear supporting cells reveals candidates for hair cell (HC) regeneration, which is limited in the adult.

AB - We explore the changes in chromatin accessibility and transcriptional programs for cochlear hair cell differentiation from postmitotic supporting cells using organoids from postnatal cochlea. The organoids contain cells with transcriptional signatures of differentiating vestibular and cochlear hair cells. Construction of trajectories identifies Lgr5+ cells as progenitors for hair cells, and the genomic data reveal gene regulatory networks leading to hair cells. We validate these networks, demonstrating dynamic changes both in expression and predicted binding sites of transcription factors (TFs) during organoid differentiation. We identify known regulators of hair cell development, Atoh1, Pou4f3, and Gfi1, and the analysis predicts the regulatory factors Tcf4, an E-protein and heterodimerization partner of Atoh1, and Ddit3, a CCAAT/enhancer-binding protein (C/EBP) that represses Hes1 and activates transcription of Wnt-signaling-related genes. Deciphering the signals for hair cell regeneration from mammalian cochlear supporting cells reveals candidates for hair cell (HC) regeneration, which is limited in the adult.

KW - ATAC sequencing

KW - CP: Stem cell research

KW - cochlea

KW - gene expression analysis

KW - sensory hair cells

KW - single-cell RNA sequencing

UR - http://www.scopus.com/inward/record.url?scp=85176111436&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85176111436&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2023.113421

DO - 10.1016/j.celrep.2023.113421

M3 - Article

C2 - 37952154

AN - SCOPUS:85176111436

SN - 2211-1247

VL - 42

JO - Cell Reports

JF - Cell Reports

IS - 11

M1 - 113421

ER -

Cochlear organoids reveal transcriptional programs of postnatal hair cell differentiation from supporting cells

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this