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NFI transcription factors provide chromatin access to maintain stem cell identity while preventing unintended lineage fate choices
by
Adam, Rene C
, Zhao, Yilin
, Paik, Seung S
, Zheng Deyou
, Ko, Joo Y
, Krueger, James G
, Lu, Catherine P
, Gur-Cohen, Shiri
, Wang, Ping
, Yang Hanseul
, Gronostajski, Richard M
, Kim, Jeong E
, Miao Yuxuan
, Infarinato, Nicole R
, Fuchs, Elaine
, Kim, Jaehwan
, Ge Yejing
in
Ablation
/ Alopecia
/ Chromatin
/ Crosstalk
/ Degeneration
/ Enhancers
/ Follicles
/ Hair
/ Homeostasis
/ Nuclear factor I
/ Regeneration
/ Stem cell transplantation
/ Stem cells
/ Transcription factors
2020
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NFI transcription factors provide chromatin access to maintain stem cell identity while preventing unintended lineage fate choices
by
Adam, Rene C
, Zhao, Yilin
, Paik, Seung S
, Zheng Deyou
, Ko, Joo Y
, Krueger, James G
, Lu, Catherine P
, Gur-Cohen, Shiri
, Wang, Ping
, Yang Hanseul
, Gronostajski, Richard M
, Kim, Jeong E
, Miao Yuxuan
, Infarinato, Nicole R
, Fuchs, Elaine
, Kim, Jaehwan
, Ge Yejing
in
Ablation
/ Alopecia
/ Chromatin
/ Crosstalk
/ Degeneration
/ Enhancers
/ Follicles
/ Hair
/ Homeostasis
/ Nuclear factor I
/ Regeneration
/ Stem cell transplantation
/ Stem cells
/ Transcription factors
2020
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NFI transcription factors provide chromatin access to maintain stem cell identity while preventing unintended lineage fate choices
by
Adam, Rene C
, Zhao, Yilin
, Paik, Seung S
, Zheng Deyou
, Ko, Joo Y
, Krueger, James G
, Lu, Catherine P
, Gur-Cohen, Shiri
, Wang, Ping
, Yang Hanseul
, Gronostajski, Richard M
, Kim, Jeong E
, Miao Yuxuan
, Infarinato, Nicole R
, Fuchs, Elaine
, Kim, Jaehwan
, Ge Yejing
in
Ablation
/ Alopecia
/ Chromatin
/ Crosstalk
/ Degeneration
/ Enhancers
/ Follicles
/ Hair
/ Homeostasis
/ Nuclear factor I
/ Regeneration
/ Stem cell transplantation
/ Stem cells
/ Transcription factors
2020
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NFI transcription factors provide chromatin access to maintain stem cell identity while preventing unintended lineage fate choices
Journal Article
NFI transcription factors provide chromatin access to maintain stem cell identity while preventing unintended lineage fate choices
2020
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Overview
Tissue homeostasis and regeneration rely on resident stem cells (SCs), whose behaviour is regulated through niche-dependent crosstalk. The mechanisms underlying SC identity are still unfolding. Here, using spatiotemporal gene ablation in murine hair follicles, we uncover a critical role for the transcription factors (TFs) nuclear factor IB (NFIB) and IX (NFIX) in maintaining SC identity. Without NFI TFs, SCs lose their hair-regenerating capability, and produce skin bearing striking resemblance to irreversible human alopecia, which also displays reduced NFIs. Through single-cell transcriptomics, ATAC-Seq and ChIP-Seq profiling, we expose a key role for NFIB and NFIX in governing super-enhancer maintenance of the key hair follicle SC-specific TF genes. When NFIB and NFIX are genetically removed, the stemness epigenetic landscape is lost. Super-enhancers driving SC identity are decommissioned, while unwanted lineages are de-repressed ectopically. Together, our findings expose NFIB and NFIX as crucial rheostats of tissue homeostasis, functioning to safeguard the SC epigenome from a breach in lineage confinement that otherwise triggers irreversible tissue degeneration.Adam, Yang et al. show that the transcription factors NFIB and NFIX promote stemness by establishing chromatin accessibility and regulating the super-enhancers that govern bulge stem cell identity.
Publisher
Nature Publishing Group
Subject
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