miR-29a/b1 Inhibits Hair Follicle Stem Cell Lineage Progression by Spatiotemporally Suppressing WNT and BMP Signaling.
Hair follicle stem cells (HFSCs) and subsequent generations of matrix progeny make lineage choices by responding to spatiotemporal signals; however, the cues driving that specification are not well understood. Here, we demonstrate that the dynamics of microRNA (miR)-29 expression are inversely proportional to HFSC lineage progression. Furthermore, we show that sustained miR-29a/b1 overexpression in anagen or telogen in mice causes a short-hair phenotype and eventual hair loss by inhibiting the proliferation of HFSCs and matrix cells and likely preventing their differentiation. Conversely, in a loss-of-function in vivo model, miR-29a/b1 deficiency accelerates HFSC lineage progression in telogen. Mechanistically, miR-29a/b1 blocks HFSC lineage specification by spatiotemporally targeting Ctnnb1, Lrp6, Bmpr1a, and Ccna2. We further show that skin-specific Lrp6 or Bmpr1a ablation partially accounts for the short-hair phenotype. Overall, these synergistic targets reveal miR-29a/b1 as a high-fidelity antagonist of HFSC lineage progression and a potential therapeutic target for hair loss.
Pubmed ID: 31747615 RIS Download
Research resources used in this publication
- B6.Cg-Tg(tetO-cre)1Jaw/J (RRID:IMSR_JAX:006234) (organism)
- B6N.129P2-Axin2tm1Wbm/J (RRID:IMSR_JAX:009120) (organism)
- B6;SJL-Tg(KRT14-rtTA)208Jek/J (RRID:IMSR_JAX:007678) (organism)
- STOCK Tg(KRT14-cre)1Amc/J (RRID:IMSR_JAX:004782) (organism)
- B6;SJL-Tg(KRT14-rtTA)208Jek/J (RRID:IMSR_JAX:007678) (organism)
- B6.Cg-Tg(tetO-cre)1Jaw/J (RRID:IMSR_JAX:006234) (organism)
- B6N.129P2-Axin2tm1Wbm/J (RRID:IMSR_JAX:009120) (organism)
- STOCK Tg(KRT14-cre)1Amc/J (RRID:IMSR_JAX:004782) (organism)
Additional research tools detected in this publication
None foundAntibodies used in this publication
- Smad1 (A-4) (RRID:AB_628261)
- Cyclin A antibody (RRID:AB_306170)
- Phospho-Smad1 (Ser463/465)/ Smad5 (Ser463/465)/ Smad9 (Ser465/467) (D5B10) Rabbit mAb (RRID:AB_2493181)
- β-Catenin (D10A8) XP® Rabbit mAb (RRID:AB_11127855)
- Mouse P-Cadherin Affinity Purified Polyclonal Ab (RRID:AB_355581)
- Axin 2 antibody [EPR2005(2)] (RRID:AB_10862550)
- Cytokeratin 15 (RRID:AB_2335914)
- Rabbit Anti-Human / Mouse beta-Catenin Antibody, Unconjugated (RRID:AB_476831)
- LRP6 (C47E12) Rabbit mAb (RRID:AB_1950408)
- Sox9 (D8G8H) Rabbit mAb #82630 (RRID:AB_2665492)
- Cleaved Caspase-3 (Asp175) (5A1E) Rabbit mAb (RRID:AB_2070042)
- Rabbit Anti-BMPR1A Polyclonal Antibody, Unconjugated (RRID:AB_722713)
- hair cortex Cytokeratin antibody [AE13] (RRID:AB_302268)
- Rabbit Anti-GAPDH Monoclonal Antibody, Unconjugated, Clone 14C10 (RRID:AB_561053)
- Trichohyalin antibody [AE15] (RRID:AB_882889)
- NFATc1 (7A6) (RRID:AB_2152503)
- Rabbit Anti-LEF1 Monoclonal Antibody, Unconjugated, Clone C18A7 (RRID:AB_659971)
- Rat Anti-BrdU Monoclonal Antibody, Unconjugated, Clone BU1 / 75 (ICR1) (RRID:AB_305426)
- Rabbit Anti-Human Ki67 (Ki-67) Monoclonal Antibody, Unconjugated, Clone SP6 (RRID:AB_149792)
- Cytokeratin 14 antibody [LL002] (RRID:AB_306091)
Associated grants
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This is a list of tools and resources that we have found mentioned in this publication.
Smad1 (A-4) (antibody)
RRID:AB_628261
This monoclonal targets Smad1 (A-4)
View all literature mentionsCyclin A antibody (antibody)
RRID:AB_306170
This polyclonal targets Cyclin A
View all literature mentionsPhospho-Smad1 (Ser463/465)/ Smad5 (Ser463/465)/ Smad9 (Ser465/467) (D5B10) Rabbit mAb (antibody)
RRID:AB_2493181
This monoclonal targets Phospho-Smad1 (Ser463/465)/ Smad5 (Ser463/465)/ Smad9 (Ser465/467)
View all literature mentionsβ-Catenin (D10A8) XP® Rabbit mAb (antibody)
RRID:AB_11127855
This monoclonal targets β-Catenin
View all literature mentionsMouse P-Cadherin Affinity Purified Polyclonal Ab (antibody)
RRID:AB_355581
This polyclonal targets Mouse P-Cadherin Affinity Purified Ab
View all literature mentionsAxin 2 antibody [EPR2005(2)] (antibody)
RRID:AB_10862550
This monoclonal targets Axin 2 antibody [EPR2005(2)]
View all literature mentionsCytokeratin 15 (antibody)
RRID:AB_2335914
This monoclonal targets Cytokeratin 15
View all literature mentionsRabbit Anti-Human / Mouse beta-Catenin Antibody, Unconjugated (antibody)
RRID:AB_476831
This unknown targets Catenin, beta
View all literature mentionsLRP6 (C47E12) Rabbit mAb (antibody)
RRID:AB_1950408
This monoclonal targets LRP6 (C47E12) Rabbit mAb
View all literature mentionsSox9 (D8G8H) Rabbit mAb #82630 (antibody)
RRID:AB_2665492
This monoclonal targets Sox9
View all literature mentionsCleaved Caspase-3 (Asp175) (5A1E) Rabbit mAb (antibody)
RRID:AB_2070042
This monoclonal targets Casp3
View all literature mentionsRabbit Anti-BMPR1A Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_722713
This polyclonal targets BMPR1A
View all literature mentionshair cortex Cytokeratin antibody [AE13] (antibody)
RRID:AB_302268
This monoclonal targets hair cortex Cytokeratin
View all literature mentionsRabbit Anti-GAPDH Monoclonal Antibody, Unconjugated, Clone 14C10 (antibody)
RRID:AB_561053
This recombinant monoclonal targets GAPDH
View all literature mentionsTrichohyalin antibody [AE15] (antibody)
RRID:AB_882889
This monoclonal targets Human Trichohyalin
View all literature mentionsNFATc1 (7A6) (antibody)
RRID:AB_2152503
This monoclonal targets NFATc1 (7A6)
View all literature mentionsRabbit Anti-LEF1 Monoclonal Antibody, Unconjugated, Clone C18A7 (antibody)
RRID:AB_659971
This monoclonal targets LEF1
View all literature mentionsRat Anti-BrdU Monoclonal Antibody, Unconjugated, Clone BU1 / 75 (ICR1) (antibody)
RRID:AB_305426
This monoclonal targets BrdU
View all literature mentionsRabbit Anti-Human Ki67 (Ki-67) Monoclonal Antibody, Unconjugated, Clone SP6 (antibody)
RRID:AB_149792
This monoclonal targets Ki67
View all literature mentionsCytokeratin 14 antibody [LL002] (antibody)
RRID:AB_306091
This monoclonal targets Cytokeratin 14
View all literature mentionsB6.Cg-Tg(tetO-cre)1Jaw/J (organism)
RRID:IMSR_JAX:006234
Mus musculus with name B6.Cg-Tg(tetO-cre)1Jaw/J from IMSR.
View all literature mentionsB6N.129P2-Axin2tm1Wbm/J (organism)
RRID:IMSR_JAX:009120
Mus musculus with name B6N.129P2-Axin2tm1Wbm/J from IMSR.
View all literature mentionsB6;SJL-Tg(KRT14-rtTA)208Jek/J (organism)
RRID:IMSR_JAX:007678
Mus musculus with name B6;SJL-Tg(KRT14-rtTA)208Jek/J from IMSR.
View all literature mentionsSTOCK Tg(KRT14-cre)1Amc/J (organism)
RRID:IMSR_JAX:004782
Mus musculus with name STOCK Tg(KRT14-cre)1Amc/J from IMSR.
View all literature mentionsB6;SJL-Tg(KRT14-rtTA)208Jek/J (organism)
RRID:IMSR_JAX:007678
Mus musculus with name B6;SJL-Tg(KRT14-rtTA)208Jek/J from IMSR.
View all literature mentionsB6.Cg-Tg(tetO-cre)1Jaw/J (organism)
RRID:IMSR_JAX:006234
Mus musculus with name B6.Cg-Tg(tetO-cre)1Jaw/J from IMSR.
View all literature mentionsB6N.129P2-Axin2tm1Wbm/J (organism)
RRID:IMSR_JAX:009120
Mus musculus with name B6N.129P2-Axin2tm1Wbm/J from IMSR.
View all literature mentionsSTOCK Tg(KRT14-cre)1Amc/J (organism)
RRID:IMSR_JAX:004782
Mus musculus with name STOCK Tg(KRT14-cre)1Amc/J from IMSR.
View all literature mentions
