Mammary Stem Cell Self-Renewal Is Regulated by Slit2/Robo1 Signaling through SNAI1 and mINSC

Autor: Michael Stensrud, Mimmi S. Ballard, Lindsay Hinck, Aurelia Mapps, Maria Pia Postiglione, Naomi Iwai, Anna Zhu, Juergen A. Knoblich
Rok vydání: 2015
Předmět:
Medical Physiology
Cell
Cell Cycle Proteins
Regenerative Medicine
Inbred C57BL
Mice
Immunologic
Receptors
Asymmetric cell division
Cell Self Renewal
Receptors
Immunologic
lcsh:QH301-705.5
Tissue homeostasis
Tumor
SNAIL
Stem Cells
ROBO
Mammary Glands
Stem Cell Self-Renewal
Cell biology
medicine.anatomical_structure
SLIT
Intercellular Signaling Peptides and Proteins
Stem Cell Research - Nonembryonic - Non-Human
Stem cell
mammary stem cell
Human
Signal Transduction
Adult stem cell
1.1 Normal biological development and functioning
Nerve Tissue Proteins
Biology
Article
asymmetric cell division
General Biochemistry
Genetics and Molecular Biology
Cell Line
Underpinning research
Inscuteable
Cell Line
Tumor
medicine
Animals
Humans
Mammary Glands
Human
breast
Cell growth
Stem Cell Research
Mice
Inbred C57BL
lcsh:Biology (General)
Generic health relevance
Biochemistry and Cell Biology
Snail Family Transcription Factors
Transcription Factors
Zdroj: Cell Reports, Vol 13, Iss 2, Pp 290-301 (2015)
Cell reports, vol 13, iss 2
Ballard, MS; Zhu, A; Iwai, N; Stensrud, M; Mapps, A; Postiglione, MP; et al.(2015). Mammary Stem Cell Self-Renewal Is Regulated by Slit2/Robo1 Signaling through SNAI1 and mINSC. Cell Reports, 13(2), 290-301. doi: 10.1016/j.celrep.2015.09.006. UC Office of the President: Research Grants Program Office (RGPO). Retrieved from: http://www.escholarship.org/uc/item/5w0487px
ISSN: 2211-1247
Popis: © 2015 The Authors. Tissue homeostasis requires somatic stem cell maintenance; however, mechanisms regulating this process during organogenesis are not well understood. Here, we identify asymmetrically renewing basal and luminal stem cells in the mammary end bud. We demonstrate that SLIT2/ROBO1 signaling regulates the choice between self-renewing asymmetric cell divisions (ACDs) and expansive symmetric cell divisions (SCDs) by governing Inscuteable (mInsc), a key member of the spindle orientation machinery, through the transcription factor Snail (SNAI1). Loss of SLIT2/ROBO1 signaling increases SNAI1 in the nucleus. Overexpression of SNAI1 increases mInsc expression, an effect that is inhibited by SLIT2 treatment. Increased mInsc does not change cell proliferation in the mammary gland (MG) but instead causes more basal cap cells to divide via SCD, at the expense of ACD, leading to more stem cells and larger outgrowths. Together, our studies provide insight into how the number of mammary stem cells is regulated by the extracellular cue SLIT2.
Databáze: OpenAIRE
Externí odkaz: