This is presentation I gave as a speaker at thematic symposium organized by Department of Microbiology and Cell Biology at IISc. Micro-environment plays a huge role in determining, how cells behave. This presentation titled as "Cells are Social Animals: peeping into the cell through its niche" gives various examples to emphasize the fact that role of niche should not be ignored while studying a system.

1. Cells are Social Animals: peeping into the cell through its niche
Anjali Arora
Research Scholar
Indian Institute of Science Bangalore

2. “What’s the use of their
having names,”
the Gnat said, “if they won’t
answer to them?”
“No use to them,” said
Alice; “but it’s useful to the
people that name them,
I suppose.”
The Complete Works of Lewis Carroll
Through the Looking-Glass
Chapter III (p. 173)

3. Niche – a term borrowed from ecology
In ecology, a niche describes a living thing’s specific interaction with its environment,
more like a job description than an address.
Species Cells
 Niche Breadth
 Niche partitioning
 Niche construction
 Niche differentiation
• Grinnellian niche- defined by the habitat and behaviour (1917)
• Eltonian niche- its relations to food and enemies (1927)
• Hutchinsonian niche- an n-dimensional hypervolume (1957)
Charles Sutherland Elton
Joseph Grinnell
G. Evelyn Hutchinson
Consistent with the chaparral habitat
Complentary physical traits (camouflaging color, short wings,
strong legs)
"The niche relationships of the California Thrasher"

4. The Origin of the Niche Concept
"Cytological demonstration of the clonal nature of spleen colonies derived from
transplanted mouse marrow cells." Becker, Andrew J., Ernest A. McCulloch, and James E. Till (1963).
"The relationship between the spleen colony-forming cell and the haemopoietic
stem cell." Blood cells, Schofield, Raymond (1978).
Once ideas must be as broad as Nature if they are to interpret Nature.
• a defined anatomic site
• a location where stem cells could be sustained and reproduce
• a place where differentiation was inhibited
• a limited space that also limited the numbers of stem cells
• a place where reversion to a stem cell phenotype could be
induced in a slightly more mature cell type
. “Decapentaplegic Is Essential for the Maintenance and Division of
Germline Stem Cells in theDrosophila Ovary." Cell , Xie, Ting, and
Allan C. Spradling (1998)
"Somatic support cells restrict germline stem cell self-renewal and
promote differentiation." Nature, Kiger, Amy A., Helen White-Cooper,
and Margaret T. Fuller. (2000)

5. Niche – Different types
Stem cell
niches
Niches
MammalsInvertebrate
Tumor
niche
Bacterial
/fungal
niche
Plants

6. Bacterial/Fungal Niche
. "Bacterial strains isolated from different niches can exhibit different patterns of
adhesion to substrata." Applied and environmental microbiology Bakker, Dewi P., et al (2004)
. "Bacterial niche-specific genome expansion is coupled with highly frequent gene
disruptions in deep-sea sediments." PloS one, Wang, Yong, et al (2011):
. "Niche-specific requirement for Hyphal wall protein 1 in virulence of Candida
albicans." PloS one , Staab, et al (2013)

7. Stem cell
niches
Niches
MammalsInvertebrate
Tumor
niche
Bacterial
/fungal
niche
Plants

8. Stem
Cell
Stem cell niche structure
ECM proteins that provide
structure, organization and
mechanical signals to the
niche
Stromal support cells- interact
directly with the stem cell and
with each other through cell-
surface receptors, gap junctions
and soluble factors
Blood vessels- that carry
systemic signals and provide
a conduit for recruitment of
inflammatory and other
circulating cells into the
niche
Neural inputs -distant
physiological cues to the stem
cell microenvironment
•The stem cell niche exhibits an asymmetric structure
•One daughter cell is maintained in the niche as a stem cell and the other daughter cell
leaves the niche to proliferate and differentiate
•Helps maintaining number of stem cells
•Organs contain a multitude of stem cell–niche units, which are often distributed
across the entire expanse of the tissue

9. Why should a stem cell need a special environment
Support
Feedback
Control
Instruments of
Coordination
Demanding
Job
Communicating
tissue status
Inter- lineage
Coordination

10. Stem cell Niche- Invertebrate Models
• Two or three GSCs (Germ line Stem Cells) at the tip the
ovariole
• In direct contact of cap cells
• Daughter cell that remains in contact of cap cell retains
‘stemness’
• Number of GSCs correlate with the number of cap cells
GSC Niche in Drosophila Ovary
GSC Niche in Drosophila Testis
• Seven to nine GSCs attached to hub cells
• GSC divides asymmetrically, giving rise to one stem cell
and one gonialblast
• SSCs also divide to generate two cyst cells, which envelop
the gonialblast
GSC Niche in C. ELEGANS
• 225 germ cells closest to the distal tip cell (DTC) are mitotic
• Those further proximal are arrested in meiotic pachytene
• The somatic DTC is required for maintaining GSCs in
mitosis
Li, et, al. (2005)

11. Stem cell Niche- Mammals
Li, et, al. (2005)
• The bulge area functions as a niche, where stem
cells resides
• Shift of stem cells from quiescent to an activated
state requires cues frm dermal papilla.
The hair follicle stem cell niche
• Limited number of stem cells at the crypt base
• Divide once a day symmetrically, daughter cell
exit the stem cell compartment
• Paneth cells – daughter cell of the stem cell
provide the stem cell niche signals
• What controls the number of Paneth cells is not
known
The intestinal crypt niche

12. Stem cell Niche- Mammals
• HSCs physically attach to a subset of
osteoblastic cells
• Jagged1 from osteoblasts, influences HSCs
through the Notch receptor
• Number of osteoblastic lining cells controls
the number of HSCs
• In vitro coculture of HSCs with osteoblasts
can expand the HSC population
• Subventricular zone (SVZ) and the
subgranular zone (SGZ) are germinal
regions in which NSCs reside
• Endothelial cells provide attachment
for SVZ and SGZ astrocytes and
generate a variety of signals that
control stem cell self-renewal and
lineage commitment
Li, et, al. (2005)
Hematopoietic stem cell niche The neural stem cell niche

13. Plant Niche
•Plant stem cells function in a population mode-individual divisions are not strictly
asymmetric
•Any given cell becomes a new stem cell or undergoes differentiation depends on
its position
• Organizing center (OC) provides the niche
for stem cells in the shoot meristem
•Quiescent center (QC) functions as organizer of
• the root stem cell niche

14. Tumor Niche - a disordered interaction
•Cancer stem cells (CSCs), a subpopulation of cells responsible for tumor initiation
and formation reside in their own unique niche cancer stem cells niche
•Is cancer stem cell phenotype an unstable and context-
dependent trait
•Cancer stem cells, do not depend solely on cell-intrinsic events but instead rely
heavily on the right microenvironment – or niche
•Unlike normal stem cell niches, which have evolved for millions of years, cancer stem
cells niche evolves in a remarkably short time
•Loss of a niche environment mainly leads to the loss of CSCs.
•Niche maintains the CSC pool, supports the growth of primary
tumors, and plays a role in reverting nontumorigenic cells into
CSCs by processes related to the EMT

15. Cancer stem
cells in
metastatic
niches
Hypoxic Regions
Invasive fronts,
perivascular sides
Normal stem cell
niches- hijacked
Premetastatic niche must evolve in order
for tumor cells to be able to engraft and
proliferate at secondary sites
Metastatic niche model

16. Exploiting the Plasticity: Transdifferentiation
•Somatic stem cells have been claimed to possess an unexpectedly broad differentiation
potential – Plasticity
•This could be induced by exposing stem cells to the extracellular developmental
signals of other lineages in mixed-cell cultures – providing an appropriate niche
Wurmser, et. al. (2004)
What will happen if
you put, stem cell ‘A’
into the niche of stem
cell ‘B’?
Why we should know
this?
•To find out , if it really
happening in our
system
•We can exploit this
knowledge

17. Transplantation Endogenous Targeting In vitro Modeling of
Development and Disease
Niche Concept Applications “Niche Market”
Ex-vivo Culture
With niche
Stem cell expansion
Stem cell loss
Without niche Alter niche
Transplantation
Untreated
Expand niche
Low Engraftment
High Engraftment
Biased production of
certain cell types

18. Niche Concept Applications “Niche Market”
Endogenous Targeting
Dysfunction of nicheLoss of stem cells
Aging or Disease
Rejuvenation
Tumor regression
Delete /Modify
Niche cells

19. Niche Concept Applications “Niche Market”
In vitro Modeling of
Development and Disease
Stem cells alone
Differentiation
Stem cells + Normal niche
Differentiation
Stem cells + Diseased niche
Differentiation
Gene Modification/ Small Molecule
Gene Modification/ Small Molecule

20. • Whether an improved understanding of stem-cell microenvironments will provide
clues about how to send stem cells down different developmental pathways, or
reactivate quiescent stem cells?
• Can understanding the niche provide novel strategies for more effectively
delivering and engrafting transplanted stem cells?
• Can niche altering drugs support stem cells transplantation therapy
• How far a system’s equilibrium can be pushed before stem cells are wiped out or
turn cancerous?
• Differences between a normal stem cell, cancer stem cell, pre- metastatic and
metastatic niches?
• How a tumor cell alters its local and distant microenvironment?
• Can niche dysfunction be the cause of other diseases?
Niche of the future- Questions Unanswered